PaperBLAST

PaperBLAST Hits for 75 a.a. (PCFVCQDKSS...)

Show query sequence

>75 a.a. (PCFVCQDKSS...)
PCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQ
KCFEVGMSKESVRND

Running BLASTp...

Found 251 similar proteins in the literature:

RARA_XENLA / P51126 Retinoic acid receptor alpha; RAR-alpha; Nuclear receptor subfamily 1 group B member 1 from Xenopus laevis (African clawed frog) (see 3 papers)
100% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for primary neurogenesis and for anteroposterior neural patterning.
  subunit: Heterodimer; with an rxr molecule. Binds DNA preferentially as a rar/rxr heterodimer (By similarity).

RARA_HUMAN / P10276 Retinoic acid receptor alpha; RAR-alpha; Nuclear receptor subfamily 1 group B member 1 from Homo sapiens (Human) (see 28 papers)
NP_000955 retinoic acid receptor alpha isoform 1 from Homo sapiens
100% identity, 16% coverage

• function: Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21152046, PubMed:37478846). Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes (PubMed:21152046, PubMed:28167758, PubMed:37478846). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:19398580, PubMed:28167758). In the absence of ligand, the RXR- RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:16417524). On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:19850744, PubMed:20215566, PubMed:37478846, PubMed:9267036). Formation of a complex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (PubMed:28167758). Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (PubMed:28167758). RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (By similarity). Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (By similarity). In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (By similarity). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (PubMed:28167758).
  subunit: Heterodimer; with RXRA (via C-terminus); association with RXRA is enhanced by pulsatile shear stress (PubMed:10698945, PubMed:10882070, PubMed:15509776, PubMed:20215566, PubMed:21152046, PubMed:28167758). Binds DNA preferentially as a heterodimer (PubMed:10698945, PubMed:28167758). RXRA serves as enhancer to induce RARA binding to RARE (PubMed:30468856). Interacts with RXRG (PubMed:28167758). Interacts with coactivators NCOA3 and NCOA6 (PubMed:10567404, PubMed:9267036). Interacts with NCOA7; the interaction requires ligand-binding (PubMed:11971969). Interacts (via the ligand-binding domain) with PRAME; the interaction is ligand (retinoic acid)-dependent (PubMed:16179254). Interacts with AKT1; the interaction phosphorylates RARA and represses transactivation (PubMed:16417524). Interacts with PRKAR1A; the interaction negatively regulates RARA transcriptional activity (PubMed:20215566). Interacts with NCOR1 and NCOR2 (PubMed:20543827). Interacts with PRMT2 (PubMed:12039952). Interacts with LRIF1 (PubMed:17455211). Interacts with ASXL1 and NCOA1 (PubMed:16606617). Interacts with ACTN4 (PubMed:22351778). In a complex with HDAC3, HDAC5 and HDAC7; the HDACs serve as corepressors of RARA, causing its deacetylation and inhibition of RARE DNA element binding; association with HDAC3, HDAC5 and HDAC7 is increased upon oscillatory shear stress (PubMed:28167758). Interacts with CDK7 (By similarity). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863).
• PML::RARA and GATA2 proteins interact via DNA templates to induce aberrant self-renewal in mouse and human hematopoietic cells.
  Katerndahl, Proceedings of the National Academy of Sciences of the United States of America 2024
  • GeneRIF: PML::RARA and GATA2 proteins interact via DNA templates to induce aberrant self-renewal in mouse and human hematopoietic cells.
• Hyperthermia promotes degradation of the acute promyelocytic leukemia driver oncoprotein ZBTB16/RARα.
  Wang, Acta pharmacologica Sinica 2023
  • GeneRIF: Hyperthermia promotes degradation of the acute promyelocytic leukemia driver oncoprotein ZBTB16/RARalpha.
• Multi-omics and machine learning reveal context-specific gene regulatory activities of PML::RARA in acute promyelocytic leukemia.
  Villiers, Nature communications 2023
  • GeneRIF: Multi-omics and machine learning reveal context-specific gene regulatory activities of PML::RARA in acute promyelocytic leukemia.
• PRMT5-mediated RNF4 methylation promotes therapeutic resistance of APL cells to As2O3 by stabilizing oncoprotein PML-RARα.
  Huang, Cellular and molecular life sciences : CMLS 2022
  • GeneRIF: PRMT5-mediated RNF4 methylation promotes therapeutic resistance of APL cells to As2O3 by stabilizing oncoprotein PML-RARalpha.
• No prognostic significance of normalized copy number of PML-RARA transcript at diagnosis in patients with acute promyelocytic leukemia.
  Rasekh, Hematology/oncology and stem cell therapy 2021 (PubMed)
  • GeneRIF: No prognostic significance of normalized copy number of PML-RARA transcript at diagnosis in patients with acute promyelocytic leukemia.
• A PML/RARα direct target atlas redefines transcriptional deregulation in acute promyelocytic leukemia.
  Tan, Blood 2021
  • GeneRIF: A PML/RARalpha direct target atlas redefines transcriptional deregulation in acute promyelocytic leukemia.
• Structural Insights into the Interaction of the Intrinsically Disordered Co-activator TIF2 with Retinoic Acid Receptor Heterodimer (RXR/RAR).
  Senicourt, Journal of molecular biology 2021 (PubMed)
  • GeneRIF: Structural Insights into the Interaction of the Intrinsically Disordered Co-activator TIF2 with Retinoic Acid Receptor Heterodimer (RXR/RAR).
• Impact of RARα and miR-138 on retinoblastoma etoposide resistance.
  Busch, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 2021 (PubMed)
  • GeneRIF: Impact of RARalpha and miR-138 on retinoblastoma etoposide resistance.
• More
• A Multi-Level Study on the Anti-Lung Cancer Mechanism of Peiminine, a Key Component of Fritillaria ussuriensis Maxim.: Integrating Quality Analysis, Network Pharmacology, Bioinformatics Analysis, and Experimental Validation
  Yang, International journal of molecular sciences 2025
• Synthetic Retinoid Sulfarotene Selectively Inhibits Tumor-Repopulating Cells of Intrahepatic Cholangiocarcinoma via Disrupting Cytoskeleton by P-Selectin/PSGL1 N-Glycosylation Blockage.
  Du, Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2025
  • “...as a pdb format file. Then, the 3D model structure of proteins (RAR, UniProt ID: P10276; FUT8, 2DE0) was downloaded from PDB database ( https://www.rcsb.org/ ). The molecular docking was conducted using AutoDock Vina 1.1.2 [ 55 ] and visualized using Discovery Studio 2018. For predicting...”
• Combination of Lycopene and Curcumin Synergistically Alleviates Testosterone-Propionate-Induced Benign Prostatic Hyperplasia in Sprague Dawley Rats via Modulating Inflammation and Proliferation
  Wang, Molecules (Basel, Switzerland) 2023
  • “...CDC25A P30304 11 Peroxisome proliferator-activated receptor alpha PPARA Q07869 12 Retinoic acid receptor alpha RARA P10276 13 Epidermal growth factor receptor erbB1 EGFR P00533 14 Serine/threonine-protein kinase AKT AKT1 P31749 15 Serine/threonine-protein kinase B-raf BRAF P15056 16 Apoptosis regulator Bcl-2 BCL2 P10415 17 Signal transducer and...”
• Computer-Aided Screening and Revealing Action Mechanism of Food-Derived Tripeptides Intervention in Acute Colitis
  Ge, International journal of molecular sciences 2022
  • “...gamma P37231 32 RAF1 RAF proto-oncogene serine/threonine-protein kinase P04049 33 RARA Retinoic acid receptor alpha P10276 34 SAHH Adenosylhomocysteinase P23526 35 STAT1 Signal transducer and activator of transcription 1-alpha/beta P42224 36 TGFB2 Transforming growth factor beta-2 proprotein P61812 37 TGFR1 TGF-beta receptor type-1 P36897 38 TGM2...”
• Network Pharmacology Analyses of the Pharmacological Targets and Therapeutic Mechanisms of Salvianolic Acid A in Myocardial Infarction
  Huang, Evidence-based complementary and alternative medicine : eCAM 2022
  • “...protein 1 P20444 Protein kinase C alpha type P23978 Sodium- and chloride-dependent GABA transporter 1 P10276 Retinoic acid receptor alpha P19634 Sodium/hydrogen exchanger 1 P06737 Glycogen phosphorylase, liver form P04035 3-Hydroxy-3-methylglutaryl-coenzyme A reductase O14939 Phospholipase D2 P56658 Adenosine deaminase P19320 Vascular cell adhesion protein 1 P48039...”
• Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects
  Gangwar, Pharmaceuticals (Basel, Switzerland) 2022
  • “...(Uniprot ID: Q03181), ii. PPAR (Uniprot ID: P37231), ( D ) i. RAR (Uniprot ID: P10276), ii. RAR (Uniprot ID: P10826), iii. RAR (Uniprot ID: P13631), ( E ) i. RXR (Uniprot ID: P19793), ii. RXR (Uniprot ID: P28702), iii. RXR (Uniprot ID: P48443), ( F...”
• Exploring the mechanism of Alisma orientale for the treatment of pregnancy induced hypertension and potential hepato-nephrotoxicity by using network pharmacology, network toxicology, molecular docking and molecular dynamics simulation
  Liao, Frontiers in pharmacology 2022
  • “...120 Immunoglobulin heavy constant gamma 1 IGHG1 P01857 Toxic 43 Retinoic acid receptor alpha RARA P10276 Treat/Toxic 121 Interleukin-1 beta IL1B P01584 Toxic 44 Retinol-binding protein 4 RBP4 P02753 Treat/Toxic 122 Interleukin-2 IL2 P60568 Toxic 45 Sex hormone-binding globulin SHBG P04278 Treat/Toxic 123 Integrin alpha-L ITGAL...”
• Demystifying the Functional Role of Nuclear Receptors in Esophageal Cancer.
  Jayaprakash, International journal of molecular sciences 2022
  • “...Pregnane X receptors (PXRs) (UniProt ID: F1DAL3), Retinoic acid receptor alpha (RAR ) (UniProt ID: P10276), Retinoic acid receptor beta (RAR ) (UniProt ID: P10826), Retinoic acid receptor gamma (RAR ) (UniProt ID: P13631), Retinoid X receptor alpha (RXR ) (UniProt ID: P19793), Retinoid X receptor...”
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XP_005220795 retinoic acid receptor alpha isoform X1 from Bos taurus
100% identity, 16% coverage

• Regulation of mammary gland sensitivity to thyroid hormones during the transition from pregnancy to lactation.
  Capuco, Experimental biology and medicine (Maywood, N.J.) 2008 (PubMed)
  • GeneRIF: Increased expression of mammary TRbeta1 and DIO2, and decreased RXRalpha, provide a mechanism to increase thyroid hormone activity within the mammary gland during lactation.

RARA_CHICK / Q90966 Retinoic acid receptor alpha; RAR-alpha; Nuclear receptor subfamily 1 group B member 1 from Gallus gallus (Chicken) (see 2 papers)
100% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for hindbrain patterning and appears to be required for skin development.
  subunit: Heterodimer; with an RXR molecule. Binds DNA preferentially as a RAR/RXR heterodimer.

XP_015136801 retinoic acid receptor beta isoform X2 from Gallus gallus
99% identity, 17% coverage

• RARβ regulates neuronal cell death and differentiation in the avian ciliary ganglion.
  Koszinowski, Developmental neurobiology 2015
  • GeneRIF: Study showed that RARB expression was vital for the timely execution of programmed cell death and was furthermore seen to have an influence on the differentiation state of the ciliary ganglion neurons

RARB_CHICK / P22448 Retinoic acid receptor beta; RAR-beta; Nuclear receptor subfamily 1 group B member 2 from Gallus gallus (Chicken) (see 3 papers)
99% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for limb and craniofacial development.
  subunit: Heterodimer; with a RXR molecule. Binds DNA preferentially as a RAR/RXR heterodimer.
• TMT-based quantitative proteomic analysis of IBDV-infected CEF cells reveals a favorable role of chicken IRF10 in IBDV replication via suppressing type-I interferon expression
  Zhang, Poultry science 2024
  • “...sequence-specific DNA binding P02272 H2AZ2 2.6 DNA binding Q90WI0 IRF10 2.4 DNA-binding transcription factor activity P22448 RARB 0.5 RNA polymerase II cis-regulatory region sequence-specific DNA binding A0A8V0XYM6 RBM43 2.8 RNA-binding A0A8V0ZK53 ZFP36L2 2.6 mRNA 3-UTR AU-rich region binding P0C1H5 H2B-VII 4.2 protein-containing complex binding O93327 H2AFY...”

RARB_COTJA / Q9W6B3 Retinoic acid receptor beta; RAR-beta; Nuclear receptor subfamily 1 group B member 2 from Coturnix japonica (Japanese quail) (Coturnix coturnix japonica) (see paper)
99% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). May be required for Sertoli cell differentiation and spermatogenesis.
  subunit: Heterodimer; with a RXR molecule. Binds DNA preferentially as a RAR/RXR heterodimer.

RARA_MOUSE / P11416 Retinoic acid receptor alpha; RAR-alpha; Nuclear receptor subfamily 1 group B member 1 from Mus musculus (Mouse) (see 11 papers)
XP_006532655 retinoic acid receptor alpha isoform X1 from Mus musculus
99% identity, 16% coverage

• function: Receptor for retinoic acid (PubMed:17205979). Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes (PubMed:17205979). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:17205979). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (By similarity). On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:17205979, PubMed:19078967, PubMed:9230306). Formation of heterocomplex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (By similarity). Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (By similarity). RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (PubMed:15901285). Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (PubMed:15901285, PubMed:17905941). In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (PubMed:10660575, PubMed:17905941). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (PubMed:19389355). Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (By similarity). In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (By similarity).
  subunit: Heterodimer; with RXRA (PubMed:17205979). Binds DNA preferentially as a heterodimer (By similarity). RXRA serves as enhancer to induce RARA binding to RARE (By similarity). Interacts with RXRG (By similarity). Interacts with NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes (PubMed:10788465, PubMed:9192892). Interacts with NCOA7; the interaction requires ligand-binding (By similarity). Interacts (via the ligand-binding domain) with PRAME; interaction is direct and ligand (retinoic acid)-dependent (By similarity). Interacts with PRKAR1A; the interaction negatively regulates RARA transcriptional activity (By similarity). Interacts with NCOR1; the interaction occurs in the absence of ligand and represses transcriptional activity (PubMed:17205979). Interacts with NCOR2 (By similarity). Interacts with PRMT2 (By similarity). Interacts with LRIF1 (By similarity). Interacts with ASXL1 and NCOA1 (By similarity). Interacts with ACTN4 (By similarity). Interacts with CDK7; the interaction is enhanced by interaction with GTF2H3 (PubMed:9230306). Interacts with GTF2H3; the interaction requires prior phosphorylation on Ser-369 which then enhances interaction with CDK7 (PubMed:19078967). In a complex with HDAC3, HDAC5 and HDAC7; the HDACs serve as corepressors of RARA, causing its deacetylation and inhibition of RARE DNA element binding; association with HDAC3, HDAC5 and HDAC7 is increased upon oscillatory shear stress (By similarity). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863).
  disruption phenotype: Seminiferous tubules of 6 month-old animals display varying degrees of testicular degeneration, with moderate to severe levels of germ-cell degeneration. Epithelial cells in the epididymis show general disorganization. Sperm count is reduced to about 1.7% of wild-type and sperm mobility reduced by half. Rara and Rarg, but not Rara and Rarb, double knockout mice exhibit growth retardation after 3 weeks. Defects are found in the growth plates with deficiency in cartilage. Growth retardation was noticable in limb sketal elements such as femurs. Early lethality and male sterility due to squamous metaplasia of the seminal vesicles and prostate are also observed.
• Adipocyte retinoic acid receptor α prevents obesity and steatohepatitis by regulating energy expenditure and lipogenesis.
  Cassim, Obesity (Silver Spring, Md.) 2024
  • GeneRIF: Adipocyte retinoic acid receptor alpha prevents obesity and steatohepatitis by regulating energy expenditure and lipogenesis.
• Retinoic acid receptor α activity in proximal tubules prevents kidney injury and fibrosis.
  DiKun, Proceedings of the National Academy of Sciences of the United States of America 2024
  • GeneRIF: Retinoic acid receptor alpha activity in proximal tubules prevents kidney injury and fibrosis.
• PML::RARA and GATA2 proteins interact via DNA templates to induce aberrant self-renewal in mouse and human hematopoietic cells.
  Katerndahl, Proceedings of the National Academy of Sciences of the United States of America 2024
  • GeneRIF: PML::RARA and GATA2 proteins interact via DNA templates to induce aberrant self-renewal in mouse and human hematopoietic cells.
• Synergistic activation of RARβ and RARγ nuclear receptors restores cell specialization during stem cell differentiation by hijacking RARα-controlled programs.
  Koshy, Life science alliance 2023
  • GeneRIF: Synergistic activation of RARbeta and RARgamma nuclear receptors restores cell specialization during stem cell differentiation by hijacking RARalpha-controlled programs.
• Retinoic acid receptor activity is required for the maintenance of type 1 innate lymphoid cells.
  Asahi, International immunology 2023 (PubMed)
  • GeneRIF: Retinoic acid receptor activity is required for the maintenance of type 1 innate lymphoid cells.
• Identifying STRN3-RARA as a new fusion gene for acute promyelocytic leukemia.
  Zhang, Blood 2023 (PubMed)
  • GeneRIF: Identifying STRN3-RARA as a new fusion gene for acute promyelocytic leukemia.
• Spinal cord retinoic acid receptor signaling gates mechanical hypersensitivity in neuropathic pain.
  Cao, Neuron 2022
  • GeneRIF: Spinal cord retinoic acid receptor signaling gates mechanical hypersensitivity in neuropathic pain.
• Retinoic Acid Receptor Alpha (RARα) in Macrophages Protects from Diet-Induced Atherosclerosis in Mice.
  Cassim, Cells 2022
  • GeneRIF: Retinoic Acid Receptor Alpha (RARalpha) in Macrophages Protects from Diet-Induced Atherosclerosis in Mice.
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NP_001083723 retinoic acid receptor alpha L homeolog from Xenopus laevis
100% identity, 17% coverage

• RIPPLY3 is a retinoic acid-inducible repressor required for setting the borders of the pre-placodal ectoderm.
  Janesick, Development (Cambridge, England) 2012
  • GeneRIF: results show role for retinoic acid receptor as a regulator of spatial patterning of the pre-placodal ectoderm (PPE)through Tbx1 and RIPPLY3; demonstrate that Ripply3, acting downstream of RAR signaling, is key player in establishing boundaries in the PPE

RARG_HUMAN / P13631 Retinoic acid receptor gamma; RAR-gamma; Nuclear receptor subfamily 1 group B member 3 from Homo sapiens (Human) (see paper)
96% identity, 17% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (By similarity).
  subunit: Homodimer. Heterodimer with a RXR molecule. Binds DNA preferentially as a RAR/RXR heterodimer. Forms a complex with PUS1 and the SRA1 RNA in the nucleus.
• FMCA-DTI: a fragment-oriented method based on a multihead cross attention mechanism to improve drug-target interaction prediction.
  Zhang, Bioinformatics (Oxford, England) 2024
  • “...P18089 True True P35462 True True P21728 True True Accuracy 90.9% DB00755-Tretinoin P48443 True True P13631 True False P00352 True True P11712 True True P04798 True True P08684 True True P24462 True True P33260 True True P10632 True True P28702 True True Accuracy 90% Second, we...”
• Clustering Protein Binding Pockets and Identifying Potential Drug Interactions: A Novel Ligand-Based Featurization Method.
  Stevenson, Journal of chemical information and modeling 2023
  • “...have known activity with different proteins. Molecule C is a RAR antagonist of UniProt ID P13631 (retinoic acid receptor gamma). 80 Molecule D binds to UniProt ID Q03181 (peroxisome proliferator-activated receptor delta). 81 Cluster #140 consists of only 11 pockets from 10 unique proteins, where the...”
• Network Pharmacology Analyses of the Pharmacological Targets and Therapeutic Mechanisms of Salvianolic Acid A in Myocardial Infarction
  Huang, Evidence-based complementary and alternative medicine : eCAM 2022
  • “...P62943 Peptidyl-prolyl cis-trans isomerase FKBP1A P19156 Potassium-transporting ATPase alpha chain 1 P50579 Methionine aminopeptidase 2 P13631 Retinoic acid receptor gamma Q8WW43 Gamma-secretase subunit APH-1B P62942 Peptidyl-prolyl cis-trans isomerase FKBP1A Q8TDS4 Hydroxycarboxylic acid receptor 2 P51639 3-Hydroxy-3-methylglutaryl-coenzyme A reductase P48443 Retinoic acid receptor RXR-gamma O14842 Free fatty...”
• Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects
  Gangwar, Pharmaceuticals (Basel, Switzerland) 2022
  • “...) i. RAR (Uniprot ID: P10276), ii. RAR (Uniprot ID: P10826), iii. RAR (Uniprot ID: P13631), ( E ) i. RXR (Uniprot ID: P19793), ii. RXR (Uniprot ID: P28702), iii. RXR (Uniprot ID: P48443), ( F ) VDR (Uniprot ID: P11473), ( G ) ERR (Uniprot...”
• Demystifying the Functional Role of Nuclear Receptors in Esophageal Cancer.
  Jayaprakash, International journal of molecular sciences 2022
  • “...receptor beta (RAR ) (UniProt ID: P10826), Retinoic acid receptor gamma (RAR ) (UniProt ID: P13631), Retinoid X receptor alpha (RXR ) (UniProt ID: P19793), Retinoid X receptor beta (RXR ) (UniProt ID: P28702), Retinoid X receptor gamma (RXR ) (UniProt ID: P48443) and Vitamin D...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2021
  • “...Systematic nomenclature NR1B1 NR1B2 NR1B3 HGNC, UniProt RARA , P10276 RARB , P10826 RARG , P13631 Agonists tretinoin [ 23 ] tretinoin [ 23 ] tretinoin [ 23 ] Sub/familyselective agonists tazarotene [ 23 ] tazarotene [ 23 ], adapalene [ 22 ] tazarotene [ 23...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2017
  • “...Systematic nomenclature NR1B1 NR1B2 NR1B3 HGNC, UniProt RARA , P10276 RARB , P10826 RARG , P13631 Agonists tretinoin [ 25 ] tretinoin [ 25 ] tretinoin [ 25 ] Sub/familyselective agonists tazarotene [ 25 ] tazarotene [ 25 ], adapalene [ 24 ] tazarotene [ 25...”
• Increasing the Level of IRS-1 and Insulin Pathway Sensitivity by Natural Product Carainterol A.
  Ma, Molecules (Basel, Switzerland) 2016
  • “...acid receptor RXR- 3.916 0.5594 3 SULT2A1 Q06520 Bile salt sulfotransferase 3.77 0.7541 4 RARG P13631 Retinoic acid receptor 3.753 0.4691 5 SRC P12931 Proto-oncogene tyrosine-protein kinase Src 3.725 0.4139 6 PTN1 P18031 Tyrosine-protein phosphatase non-receptor type 1 3.725 0.4139 7 NR1I3 Q14994 Nuclear receptor subfamily...”
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RARG_MOUSE / P18911 Retinoic acid receptor gamma; RAR-gamma; Nuclear receptor subfamily 1 group B member 3 from Mus musculus (Mouse) (see 4 papers)
96% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors (By similarity). Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function.
  subunit: Homodimer (By similarity). Heterodimer with a RXR molecule (By similarity). Binds DNA preferentially as a RAR/RXR heterodimer (By similarity). Forms a complex with PUS1 and the SRA1 RNA in the nucleus.
  disruption phenotype: Rarg and Rarb double null mice exhibit growth retardation 3 weeks after birth. Defects are found in the growth plates with deficiency in cartilage. Growth retardation was noticable in limb sketal elements such as femurs. Early lethality and male sterility due to squamous metaplasia of the seminal vesicles and prostate are also observed. Isoform 2 mutants appear normal. The Rarg and Cyp26b1 double null mutation is able to partially rescue limb skeletal morphology without restoring normal expression of proximo-distal patterning genes.
• Exploring the "dark matter" of a mammalian proteome by protein structure and function modeling.
  Brylinski, Proteome science 2013
  • “...Esrra Steroid hormone receptor ERR1 4 ENSMUSP00000101214 115 P19785 Esr1 Estrogen receptor 5 ENSMUSP00000067266 115 P18911 Rarg Retinoic acid receptor gamma 6 ENSMUSP00000076491 114 P28700 Rxva Retinoic acid receptor RXR-alpha 7 ENSMUSP00000106051 114 O08537 Esr2 Estrogen receptor beta 8 ENSMUSP00000027649 113 P45448 Nr5a2 Nuclear receptor subfamily...”

NP_001128721 retinoic acid receptor gamma isoform 1 from Rattus norvegicus
96% identity, 16% coverage

• Ectopic expression of retinoic acid receptors and change of myocardial structure in the offspring heart with vitamin A deficiency.
  Feng, Journal of nutritional science and vitaminology 2012 (PubMed)
  • GeneRIF: We showed that the embryo hearts from vitamin A insufficient groups exhibited ultrastructural changes and significantly lowe expression of GATA-4, RARalpha and gamma, and higher expression of RXRalpha and beta.
• Ethanol impairs activation of retinoic acid receptors in cerebellar granule cells in a rodent model of fetal alcohol spectrum disorders.
  Kumar, Alcoholism, clinical and experimental research 2010
  • GeneRIF: Retinoic acid receptor gamma expression is decreased in cerebellar granule cells in an animal model of fetal alcohol syndrome.

RARA_NOTVI / P18514 Retinoic acid receptor alpha; RAR-alpha; Nuclear receptor subfamily 1 group B member 1 from Notophthalmus viridescens (Eastern newt) (Triturus viridescens) (see 2 papers)
99% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Retinoic acid signaling appears to be involved in specifying proximal-distal axis in limb regeneration.
  subunit: Heterodimer; with an rxr molecule. Binds DNA preferentially as a rar/rxr heterodimer.

RARB_HUMAN / P10826 Retinoic acid receptor beta; RAR-beta; HBV-activated protein; Nuclear receptor subfamily 1 group B member 2; RAR-epsilon from Homo sapiens (Human) (see 6 papers)
NP_001277145 retinoic acid receptor beta isoform 3 from Homo sapiens
97% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors (PubMed:12554770). The RXRA/RARB heterodimer can act as a repressor on the DR1 element and as an activator on the DR5 element (PubMed:29021580). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity).
  subunit: Homodimer (By similarity). Heterodimer; with a RXR molecule (By similarity). Binds DNA preferentially as a RAR/RXR heterodimer (By similarity). Heterodimerizes (via NR LBD) with RXRA (PubMed:29021580). Interacts weakly with NCOR2 (PubMed:12554770).
• Mechanistic Insights Into <i>Ganoderma Lucidum</i> for Diabetes Treatment via Network Pharmacology and Validation
  Guo, Diabetes, metabolic syndrome and obesity : targets and therapy 2025 (no snippet)
• A Multi-Level Study on the Anti-Lung Cancer Mechanism of Peiminine, a Key Component of Fritillaria ussuriensis Maxim.: Integrating Quality Analysis, Network Pharmacology, Bioinformatics Analysis, and Experimental Validation
  Yang, International journal of molecular sciences 2025
• Combination of Lycopene and Curcumin Synergistically Alleviates Testosterone-Propionate-Induced Benign Prostatic Hyperplasia in Sprague Dawley Rats via Modulating Inflammation and Proliferation
  Wang, Molecules (Basel, Switzerland) 2023
  • “...beta ESR2 Q92731 5 Vitamin D receptor VDR P11473 6 Retinoic acid receptor beta RARB P10826 7 MAP kinase ERK2 MAPK1 P28482 8 MAP kinase p38 alpha MAPK14 Q16539 9 Histone deacetylase 1 HDAC1 Q13547 10 Dual-specificity phosphatase Cdc25A CDC25A P30304 11 Peroxisome proliferator-activated receptor alpha...”
• OncoRTT: Predicting novel oncology-related therapeutic targets using BERT embeddings and omics features
  Thafar, Frontiers in genetics 2023
  • “...to colorectal cancer FBLN7 Q53RD9 0.9769 Fibulin 7 0 Linked to other kidney diseases RARB P10826 0.9760 Retinoic Acid Receptor Beta 13 Text mining, Drugs TABLE 8 Top 10-ranked novel predicted therapeutic targets based on the prediction score for lung cancer with the number and type...”
• Investigating the Mechanisms of Pollen Typhae in the Treatment of Diabetic Retinopathy Based on Network Pharmacology and Molecular Docking
  Zhou, Evidence-based complementary and alternative medicine : eCAM 2022
  • “...domains-containing protein 3 Q96P20 PDE4A cAMP-specific 3,5-cyclic phosphodiesterase 4A P27815 RARB Retinoic acid receptor beta P10826 Table 3 The top 20 signaling pathways with related genes. Term Pathway Genes P value hsa05200 Pathways in cancer JUN, NOS2, MMP2, PTGER3, PTGS2, MMP9, EGFR, PGF, IGF1R, VEGFA, AR,...”
• Network Pharmacology Analyses of the Pharmacological Targets and Therapeutic Mechanisms of Salvianolic Acid A in Myocardial Infarction
  Huang, Evidence-based complementary and alternative medicine : eCAM 2022
  • “...salvianolic acid A by TargetNet web service. Uniprot ID Protein P51661 Corticosteroid 11-beta-dehydrogenase isozyme 2 P10826 Retinoic acid receptor beta Q86TI2 Dipeptidyl peptidase 9 Q923Y8 Trace amine-associated receptor 1 P35463 Endothelin B receptor P13497 Bone morphogenetic protein 1 P20444 Protein kinase C alpha type P23978 Sodium-...”
• Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects
  Gangwar, Pharmaceuticals (Basel, Switzerland) 2022
  • “...(Uniprot ID: P37231), ( D ) i. RAR (Uniprot ID: P10276), ii. RAR (Uniprot ID: P10826), iii. RAR (Uniprot ID: P13631), ( E ) i. RXR (Uniprot ID: P19793), ii. RXR (Uniprot ID: P28702), iii. RXR (Uniprot ID: P48443), ( F ) VDR (Uniprot ID: P11473),...”
• PHACT: Phylogeny-Aware Computing of Tolerance for Missense Mutations
  Kuru, Molecular biology and evolution 2022
  • “...unless there was a drastic decrease in evolutionary distance. For example, in the tree of P10826, 328 out of 999 nodes were within a one-unit distance (namely, less than or equal to one substitution per site) to the query sequence (human). The branch length distances and...”
• More
• RARB associated with MSI, affects progression and prognosis of gastric cancer.
  Cai, BMC gastroenterology 2024
  • GeneRIF: RARB associated with MSI, affects progression and prognosis of gastric cancer.
• A De Novo Noncoding RARB Variant Associated with Complex Microphthalmia Alters a Putative Regulatory Element.
  Replogle, Human mutation 2024
  • GeneRIF: A De Novo Noncoding RARB Variant Associated with Complex Microphthalmia Alters a Putative Regulatory Element.
• Epigenetic regulation of RARB overcomes the radio-resistance of colorectal carcinoma cells via cancer stem cells.
  Shu, Journal of radiation research 2023
  • GeneRIF: Epigenetic regulation of RARB overcomes the radio-resistance of colorectal carcinoma cells via cancer stem cells.
• Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta.
  Caron, Genetics in medicine : official journal of the American College of Medical Genetics 2023
  • GeneRIF: Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta.
• Hepatocyte Nuclear Factor 4α (HNF4α) Plays a Controlling Role in Expression of the Retinoic Acid Receptor β (RARβ) Gene in Hepatocytes.
  Zolfaghari, International journal of molecular sciences 2023
  • GeneRIF: Hepatocyte Nuclear Factor 4alpha (HNF4alpha) Plays a Controlling Role in Expression of the Retinoic Acid Receptor beta (RARbeta) Gene in Hepatocytes.
• Promoter hypermethylation of RARB and GSTP1 genes in plasma cell-free DNA as breast cancer biomarkers in Peruvian women.
  Danos, Molecular genetics & genomic medicine 2023
  • GeneRIF: Promoter hypermethylation of RARB and GSTP1 genes in plasma cell-free DNA as breast cancer biomarkers in Peruvian women.
• Retinoic Acid Receptor β Loss in Hepatocytes Increases Steatosis and Elevates the Integrated Stress Response in Alcohol-Associated Liver Disease.
  Melis, International journal of molecular sciences 2023
  • GeneRIF: Retinoic Acid Receptor beta Loss in Hepatocytes Increases Steatosis and Elevates the Integrated Stress Response in Alcohol-Associated Liver Disease.
• DNA hypermethylation of CADM1, PAX5, WT1, RARβ, and PAX6 genes in oropharyngeal cancer associated with human papillomavirus.
  Birknerová, Epigenetics 2022
  • GeneRIF: DNA hypermethylation of CADM1, PAX5, WT1, RARbeta, and PAX6 genes in oropharyngeal cancer associated with human papillomavirus.
• More

XP_017455067 retinoic acid receptor beta isoform X1 from Rattus norvegicus
97% identity, 16% coverage

• Maternal vitamin A deficiency impairs cholinergic and nitrergic neurons, leading to gastrointestinal dysfunction in rat offspring via RARβ.
  Tan, Life sciences 2021 (PubMed)
  • GeneRIF: Maternal vitamin A deficiency impairs cholinergic and nitrergic neurons, leading to gastrointestinal dysfunction in rat offspring via RARbeta.
• High dietary fat-induced obesity in Wistar rats and type 2 diabetes in nonobese Goto-Kakizaki rats differentially affect retinol binding protein 4 expression and vitamin A metabolism.
  Shirai, Nutrition research (New York, N.Y.) 2016 (PubMed)
  • GeneRIF: RARbeta in the kidney, which was induced in a retinoic acid-dependent manner, was downregulated by 90% in nonobese Goto-Kakizaki rats.
• Neuronal RARβ Signaling Modulates PTEN Activity Directly in Neurons and via Exosome Transfer in Astrocytes to Prevent Glial Scar Formation and Induce Spinal Cord Regeneration.
  Goncalves, The Journal of neuroscience : the official journal of the Society for Neuroscience 2015
  • GeneRIF: Activation of RARBeta in the neuron induces its transfer into astrocytes where it prevents scar formation.
• Neuritogenic activity of trichostatin A in adult rat retinal ganglion cells through acetylation of histone H3 lysine 9 and RARβ induction.
  Koriyama, Journal of pharmacological sciences 2014 (PubMed)
  • GeneRIF: Its expression is involved in axonal regeneration in CNS neurons.
• Effect of marginal vitamin A deficiency during pregnancy on retinoic acid receptors and N-methyl-D-aspartate receptor expression in the offspring of rats.
  Zhang, The Journal of nutritional biochemistry 2011 (PubMed)
  • GeneRIF: There was no significant difference in RARbeta between the groups
• Roles of vitamin A and macula flava in maintaining vocal folds.
  Tateya, The Annals of otology, rhinology, and laryngology 2008 (PubMed)
  • GeneRIF: Immunohistochemical analysis of normal vocal folds revealed expression of retinoic acid receptor a in vocal fold stellate cells.

NP_001276690 retinoic acid receptor beta isoform beta1 from Mus musculus
97% identity, 16% coverage

• Synergistic activation of RARβ and RARγ nuclear receptors restores cell specialization during stem cell differentiation by hijacking RARα-controlled programs.
  Koshy, Life science alliance 2023
  • GeneRIF: Synergistic activation of RARbeta and RARgamma nuclear receptors restores cell specialization during stem cell differentiation by hijacking RARalpha-controlled programs.
• Retinoic Acid Receptor β Loss in Hepatocytes Increases Steatosis and Elevates the Integrated Stress Response in Alcohol-Associated Liver Disease.
  Melis, International journal of molecular sciences 2023
  • GeneRIF: Retinoic Acid Receptor beta Loss in Hepatocytes Increases Steatosis and Elevates the Integrated Stress Response in Alcohol-Associated Liver Disease.
• Retinoic acid receptor beta protects striatopallidal medium spiny neurons from mitochondrial dysfunction and neurodegeneration.
  Ciancia, Progress in neurobiology 2022 (PubMed)
  • GeneRIF: Retinoic acid receptor beta protects striatopallidal medium spiny neurons from mitochondrial dysfunction and neurodegeneration.
• Transgene integration causes RARB downregulation in homozygous Tg4-42 mice.
  Hinteregger, Scientific reports 2020
  • GeneRIF: Transgene integration causes RARB downregulation in homozygous Tg4-42 mice.
• Retinoic Acid Receptor-β Is Downregulated in Hepatocellular Carcinoma and Cirrhosis and Its Expression Inhibits Myosin-Driven Activation and Durotaxis in Hepatic Stellate Cells.
  Cortes, Hepatology (Baltimore, Md.) 2019 (PubMed)
  • GeneRIF: significant reduction in expression in fibrotic liver
• The regulation of mitochondrial dynamics in neurite outgrowth by retinoic acid receptor β signaling.
  Trigo, FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2019
  • GeneRIF: RAR-beta signaling promotes the binding of the mitochondria to the anchoring protein, glucose-related protein 75, at the growing tip of neurite, thus allowing them to provide energy and metabolic roles required for neurite outgrowth.
• Epithelial retinoic acid receptor β regulates serum amyloid A expression and vitamin A-dependent intestinal immunity.
  Gattu, Proceedings of the National Academy of Sciences of the United States of America 2019
  • GeneRIF: Studied role of dietary vitamin A, intestinal immunity and amyloid A expression regulation through retinoic acid receptor beta (Rarb.)
• Combinatorial knockout of RARα, RARβ, and RARγ completely abrogates transcriptional responses to retinoic acid in murine embryonic stem cells.
  Laursen, The Journal of biological chemistry 2018
  • GeneRIF: This study used CRISPR technology to introduce biallelic frameshift mutations in RAR alpaha, RAR beta, and RAR gamma, thereby abrogating all RAR functions in murine embryonic stem cells. RAR-null cells display no changes in transcripts in response to All-trans-retinoic acid (RA), demonstrating that the RARs are essential for the regulation of all transcripts in murine embryonic stem cells in response to RA.
• More

RARB_MOUSE / P22605 Retinoic acid receptor beta; RAR-beta; Nuclear receptor subfamily 1 group B member 2 from Mus musculus (Mouse) (see paper)
97% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors (By similarity). The RXRA/RARB heterodimer can act as a repressor on the DR1 element and as an activator on the DR5 element (By similarity). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (PubMed:19389355).
  subunit: Homodimer (By similarity). Heterodimer; with a RXR molecule (By similarity). Binds DNA preferentially as a RAR/RXR heterodimer (By similarity). Heterodimerizes (via NR LBD) with RXRA (By similarity). Interacts weakly with NCOR2 (By similarity).
  disruption phenotype: Rarb and Rarg, but not Rarb and Rara, double null mice exhibit growth retardation 3 weeks after birth. Defects are found in the growth plates with deficiency in cartilage. Growth retardation was noticable in limb sketal elements such as femurs. Early lethality and male sterility due to squamous metaplasia of the seminal vesicles and prostate are also observed. Isoform 2 mutants appear normal.
• Molecular characterization of thyroid hormone receptor beta from Schistosoma japonicum and assessment of its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice
  Qiu, Parasites & vectors 2012
  • “..., AAR29359.1; SjTHR, Schistosoma japonicum , HRARa, Homo sapiens , P10276; MRARb, Mus musculus , P22605; SmRXR, schistosoma mansoni , AF094759. mRNA expression level of SjTHR in the development of schistosomula into adult worms obtained from rabbit Quantitative real-time PCR was performed to evaluate relative mRNA...”

XP_005156109 retinoic acid receptor alpha-A isoform X1 from Danio rerio
97% identity, 17% coverage

• Retinoic acid receptor subtype-specific transcriptotypes in the early zebrafish embryo.
  Samarut, Molecular endocrinology (Baltimore, Md.) 2014
  • GeneRIF: Retinoic acid (RA)-responsive genes are differentially sensitive to alterations in the RA pathway and, in particular, cyp26a1 and raraa are under a high pressure to maintain signaling integrity.

NP_001076779 retinoic acid receptor gamma-B from Danio rerio
96% identity, 16% coverage

• Rargb regulates organ laterality in a zebrafish model of right atrial isomerism.
  Garnaas, Developmental biology 2012
  • GeneRIF: Rargb knockdown results in bilateral livers but does not impact organ size, revealing a unique role for Rargb in conferring left-right positional information

RARGA_DANRE / Q91392 Retinoic acid receptor gamma-A; RAR-gamma-A; zRAR gamma; Nuclear receptor subfamily 1 group B member 3-A; RAR-gamma-2 from Danio rerio (Zebrafish) (Brachydanio rerio) (see 4 papers)
96% identity, 15% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for hindbrain development and for the development of pharyngeal arches.
  subunit: Heterodimer; with an rxr molecule. Binds DNA preferentially as a rar/rxr heterodimer.

Q15156 PML-RAR protein from Homo sapiens
100% identity, 9% coverage

• Massive peptide sharing between viral and human proteomes
  Kanduc, Peptides 2008
  • “...Q4G186; Q572P5; CPNE8_HUMAN; ITM2B_HUMAN; Q6ZR04; Q6ZT02; TCP10_HUMAN; Q2HIZ2; Q86UC7; LRC24_HUMAN; Q3SX69; Q5JXA9; Q96CG5; Q5JZG9; MYO3B_HUMAN; Q15156; Q86TU2; Q9Y5L9; CG010_HUMAN; Q86VM9; Q5T932; Q8N7D3; SPG11_HUMAN; UB2V1_HUMAN; Q9Y2A3; BR44_HUMAN; Q8NBM8; Q6ZUE1; Q562S5; Q9GZU2; Q8N7G4; Q96DU8; Q8N7E6; Q14560; Q5SYX8; Q96KH8; Q96GK3; ATP5H_HUMAN; Q5TDQ5; SURF6_HUMAN; Q86TC9; Q3MI86; Q96NT9; Q7Z4A2; CCD70_HUMAN; STX1C_HUMAN;...”

RARG_NOTVI / P18516 Retinoic acid receptor gamma; RAR-gamma; Nuclear receptor subfamily 1 group B member 3; Retinoic acid receptor delta; RAR-delta from Notophthalmus viridescens (Eastern newt) (Triturus viridescens) (see paper)
95% identity, 15% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity).
  subunit: Heterodimer; with a RXR molecule. Binds DNA preferentially as a RAR/RXR heterodimer.

RARGB_DANRE / A2T928 Retinoic acid receptor gamma-B; RAR-gamma-B; Nuclear receptor subfamily 1 group B member 3-B from Danio rerio (Zebrafish) (Brachydanio rerio) (see 2 papers)
95% identity, 15% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for hindbrain development.
  subunit: Heterodimer; with an rxr molecule. Binds DNA preferentially as a rar/rxr heterodimer.

RARAA_DANRE / Q90271 Retinoic acid receptor alpha-A; RAR-alpha-A; Nuclear receptor subfamily 1 group B member 1-A; Retinoic acid receptor alpha; zRAR alpha; Retinoic acid receptor alpha-2.A; RAR-alpha-2.A from Danio rerio (Zebrafish) (Brachydanio rerio) (see 3 papers)
97% identity, 17% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for hindbrain patterning.
  subunit: Heterodimer; with an rxr molecule. Binds DNA preferentially as a rar/rxr heterodimer.

RARG_XENLA / P28699 Retinoic acid receptor gamma; RAR-gamma; Nuclear receptor subfamily 1 group B member 3 from Xenopus laevis (African clawed frog) (see 2 papers)
92% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity).
  subunit: Heterodimer; with a rxr molecule. Binds DNA preferentially as a rar/rxr heterodimer.

5uanB / P10826 Crystal structure of multi-domain rar-beta-rxr-alpha heterodimer on DNA (see paper)
97% identity, 24% coverage

• Ligands: peptide; dna; zinc ion; retinoic acid (5uanB)

6xwgD / P10276 Crystal structure of the human rxr/rar DNA-binding domain heterodimer bound to the human rarb2 dr5 response element (see paper)
100% identity, 94% coverage

• Ligands: dna; zinc ion (6xwgD)

RARAB_DANRE / Q7ZTI3 Retinoic acid receptor alpha-B; RAR-alpha-B; Nuclear receptor subfamily 1 group B member 1-B; Retinoic acid receptor alpha-2.B; RAR-alpha-2.B from Danio rerio (Zebrafish) (Brachydanio rerio) (see 2 papers)
NP_571474 retinoic acid receptor alpha-B from Danio rerio
96% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for hindbrain development and, in lateral plate mesoderm, for specification of the pectoral fins.
  subunit: Heterodimer; with an rxr molecule. Binds DNA preferentially as a rar/rxr heterodimer.
• Plasticity of photoreceptor-generating retinal progenitors revealed by prolonged retinoic acid exposure.
  Stevens, BMC developmental biology 2011
  • GeneRIF: The RA receptors RXR gamma and RAR alpha-b are expressed in patterns consistent with mediating the effects of RA on photoreceptors.

LOC574567 retinoic acid receptor alpha-A from Strongylocentrotus purpuratus
89% identity, 12% coverage

• Thyroid hormone membrane receptor binding and transcriptional regulation in the sea urchin Strongylocentrotus purpuratus
  Taylor, Frontiers in endocrinology 2023
  • “...the TH receptor beta ortholog, as well as retinoic acid receptor alpha and beta (RAR; LOC574567 and LOC100887874). Most upregulated of the nuclear receptors was a putative ortholog of liver receptor homolog 1 (LRH-1; LOC587072). Intriguingly, one strongly upregulated nuclear receptor has no firm ortholog in...”

NP_001071806 nuclear receptor from Ciona intestinalis
80% identity, 12% coverage

• Transcriptional regulation of the retinoic acid receptor in the dorsal midline epidermis in the Ciona intestinalis embryo.
  Koyano, Development, growth & differentiation 2009 (PubMed)
  • GeneRIF: Transcriptional regulation of the retinoic acid receptor in the dorsal midline epidermis.

LOC100887874 nuclear receptor subfamily 1 group D member 1 from Strongylocentrotus purpuratus
74% identity, 13% coverage

• Thyroid hormone membrane receptor binding and transcriptional regulation in the sea urchin Strongylocentrotus purpuratus
  Taylor, Frontiers in endocrinology 2023
  • “...receptor beta ortholog, as well as retinoic acid receptor alpha and beta (RAR; LOC574567 and LOC100887874). Most upregulated of the nuclear receptors was a putative ortholog of liver receptor homolog 1 (LRH-1; LOC587072). Intriguingly, one strongly upregulated nuclear receptor has no firm ortholog in chordates but...”

E78C_DROME / P45447 Ecdysone-induced protein 78C; DR-78; Nuclear receptor subfamily 1 group E member 1 from Drosophila melanogaster (Fruit fly) (see 2 papers)
NP_001246862 Ecdysone-induced protein 78C, isoform D from Drosophila melanogaster
66% identity, 8% coverage

• function: Induces the early late puff 78C which triggers puparium formation and development.
• The Drosophila E78 nuclear receptor regulates dietary triglyceride uptake and systemic lipid levels.
  Praggastis, Developmental dynamics : an official publication of the American Association of Anatomists 2021
  • GeneRIF: The Drosophila E78 nuclear receptor regulates dietary triglyceride uptake and systemic lipid levels.
• Ecdysone response gene E78 controls ovarian germline stem cell niche formation and follicle survival in Drosophila.
  Ables, Developmental biology 2015
  • GeneRIF: Ecdysone response gene E78 controls ovarian germline stem cell niche formation and follicle survival in Drosophila.

XP_019847140 probable nuclear hormone receptor HR3 isoform X1 from Bactrocera dorsalis
63% identity, 8% coverage

• Controlling the development of the dengue vector Aedes aegypti using HR3 RNAi transgenic Chlamydomonas
  Fei, PloS one 2020
  • “...Drosophila Miranda (DmHR3X1, XP_017149048), Stomoxys calcitrans (ScHR3X2, XP_013103855), Rhagoletis zephyria (RZHR3X2, XP_017466500), Bactrocera dorsalis (BdHR3X1, XP_019847140), Zeugodacus cucurbitae (ZcHR3X1, XP_011182274), Bactrocera latifrons (BlHR3, XP_018799932), Anopheles sinensis (AsHR3, KFB44899), Aedes albopictus (AalHR3X5, XP_019549827), and Aedes aegypti (AaHR3, AF230281, AAEL009588-PA). The DNA-binding domain (C domain), hinge region (D...”
  • “...Drosophila miranda (DmHR3X1, XP_017149048), Stomoxys calcitrans (ScHR3X2, XP_013103855), Rhagoletis zephyria (RZHR3X2, XP_017466500), Bactrocera dorsalis (BdHR3X1, XP_019847140), Zeugodacus cucurbitae (ZcHR3X1, XP_011182274), Bactrocera latifrons (BlHR3, XP_018799932), Anopheles sinensis (AsHR3, KFB44899), Aedes albopictus (AalHR3X5, XP_019549827), and Aedes aegypti (AaHR3, AF230281, AAEL009588-PA). Neighbor-joining phylogenetic tree was constructed based on protein...”

XP_018799932 uncharacterized protein LOC108975688 from Bactrocera latifrons
63% identity, 8% coverage

• Controlling the development of the dengue vector Aedes aegypti using HR3 RNAi transgenic Chlamydomonas
  Fei, PloS one 2020
  • “...Rhagoletis zephyria (RZHR3X2, XP_017466500), Bactrocera dorsalis (BdHR3X1, XP_019847140), Zeugodacus cucurbitae (ZcHR3X1, XP_011182274), Bactrocera latifrons (BlHR3, XP_018799932), Anopheles sinensis (AsHR3, KFB44899), Aedes albopictus (AalHR3X5, XP_019549827), and Aedes aegypti (AaHR3, AF230281, AAEL009588-PA). The DNA-binding domain (C domain), hinge region (D domain), and ligand-binding domain (E/F domain) identified in...”
  • “...Rhagoletis zephyria (RZHR3X2, XP_017466500), Bactrocera dorsalis (BdHR3X1, XP_019847140), Zeugodacus cucurbitae (ZcHR3X1, XP_011182274), Bactrocera latifrons (BlHR3, XP_018799932), Anopheles sinensis (AsHR3, KFB44899), Aedes albopictus (AalHR3X5, XP_019549827), and Aedes aegypti (AaHR3, AF230281, AAEL009588-PA). Neighbor-joining phylogenetic tree was constructed based on protein alignments of HR3 proteins using ClustalX2. pMaa7IR/HR3IR transgenic...”

NP_003289 nuclear receptor subfamily 2 group C member 2 isoform 1 from Homo sapiens
61% identity, 12% coverage

• TR4 worsen urosepsis by regulating GSDMD.
  Wang, European journal of medical research 2024
  • GeneRIF: TR4 worsen urosepsis by regulating GSDMD.
• Thrombospondin-1 Regulates Trophoblast Necroptosis via NEDD4-Mediated Ubiquitination of TAK1 in Preeclampsia.
  Hu, Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2024
  • GeneRIF: Thrombospondin-1 Regulates Trophoblast Necroptosis via NEDD4-Mediated Ubiquitination of TAK1 in Preeclampsia.
• Structures of human TR4LBD-JAZF1 and TR4DBD-DNA complexes reveal the molecular basis of transcriptional regulation.
  Liu, Nucleic acids research 2023
  • GeneRIF: Structures of human TR4LBD-JAZF1 and TR4DBD-DNA complexes reveal the molecular basis of transcriptional regulation.
• Effects of transforming growth factor beta-activated kinase 1 (TAK1) on apoptosis of HK-2 cells in the high glucose environment.
  Wang, Bioengineered 2022
  • GeneRIF: Effects of transforming growth factor beta-activated kinase 1 (TAK1) on apoptosis of HK-2 cells in the high glucose environment.
• Small extracellular vesicle-mediated miR-320e transmission promotes osteogenesis in OPLL by targeting TAK1.
  Xu, Nature communications 2022
  • GeneRIF: Small extracellular vesicle-mediated miR-320e transmission promotes osteogenesis in OPLL by targeting TAK1.
• HDAC6-dependent deacetylation of TAK1 enhances sIL-6R release to promote macrophage M2 polarization in colon cancer.
  Xu, Cell death & disease 2022
  • GeneRIF: HDAC6-dependent deacetylation of TAK1 enhances sIL-6R release to promote macrophage M2 polarization in colon cancer.
• Use of miR‑145 and testicular nuclear receptor 4 inhibition to reduce chemoresistance to docetaxel in prostate cancer.
  Zhu, Oncology reports 2021
  • GeneRIF: Use of miR145 and testicular nuclear receptor 4 inhibition to reduce chemoresistance to docetaxel in prostate cancer.
• The stabilization of yes-associated protein by TGFβ-activated kinase 1 regulates the self-renewal and oncogenesis of gastric cancer stem cells.
  Wang, Journal of cellular and molecular medicine 2021
  • GeneRIF: The stabilization of yes-associated protein by TGFbeta-activated kinase 1 regulates the self-renewal and oncogenesis of gastric cancer stem cells.
• More

NR2C2_HUMAN / P49116 Nuclear receptor subfamily 2 group C member 2; Orphan nuclear receptor TAK1; Orphan nuclear receptor TR4; Testicular receptor 4 from Homo sapiens (Human) (see 9 papers)
61% identity, 12% coverage

• function: Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior (By similarity). Activates transcriptional activity of LHCG. Antagonist of PPARA-mediated transactivation.
  subunit: Homodimer; can bind DNA as homodimer (By similarity). Heterodimer; binds DNA as a heterodimer with NR2C1 required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with PCAF; the interaction preferentially occurs on the non-phosphorylated form and induces NR2C2-mediated transactivation activity and does not require the ligand-binding domain (By similarity). Interacts (MAPK-mediated phosphorylated form) with NRIP1; the interaction promotes repression of NR2C2-mediated activity (PubMed:9556573). Interacts with NR2C2AP; the interaction represses selective NR2C2-mediated transcriptional activity (PubMed:12486131). Interacts with NLRP10 (PubMed:22672233). Interacts (via ligand-binding region) with transcriptional corepressor JAZF1; the interaction promotes NR2C2-mediated transcriptional repression (PubMed:15302918).
• THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2021
  • “...2 Testicular receptor 4 Systematic nomenclature NR2C1 NR2C2 HGNC, UniProt NR2C1 , P13056 NR2C2 , P49116 Endogenous agonists retinol [ 169 ], tretinoin [ 169 ] Comments Forms a heterodimer with TR4; gene disruption appears without effect on testicular development or function [ 130 ]. Forms...”
• Glycogen synthase kinase (GSK)-3 and the double-strand RNA-dependent kinase, PKR: When two kinases for the common good turn bad
  Piazzi, Biochimica et biophysica acta. Molecular cell research 2020
  • “...factor; involved in cell growth, ribosome biogenesis, proliferation and apoptosis X X X (T58) X P49116 NR2C2 Nuclear receptor subfamily 2 group C member 2 Orphan nuclear receptor that can act as a transcriptional activator or repressor; involved in early embryonic development and spermatogenesis; represses estrogen...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2017
  • “...2 Testicular receptor 4 Systematic nomenclature NR2C1 NR2C2 HGNC, UniProt NR2C1 , P13056 NR2C2 , P49116 Endogenous agonists retinol [ 169 ], tretinoin [ 169 ] Comments Forms a heterodimer with TR4; gene disruption appears without effect on testicular development or function [ 132 ]. Forms...”
• The Concise Guide to PHARMACOLOGY 2015/16: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2015
  • “...2 Testicular receptor 4 Systematic nomenclature NR2C1 NR2C2 HGNC, UniProt NR2C1 , P13056 NR2C2 , P49116 Endogenous agonists retinol (Selective) [ 173 ], tretinoin (Selective) [ 173 ] Comments Forms a heterodimer with TR4; gene disruption appears without effect on testicular development or function [ 135...”
• The Concise Guide to PHARMACOLOGY 2013/14: nuclear hormone receptors
  Alexander, British journal of pharmacology 2013
  • “...Testicular receptor 2 Testicular receptor 4 Systematic nomenclature NR2C1 NR2C2 HGNC, UniProt NR2C1, P13056 NR2C2, P49116 Endogenous agonists (pKi) all-trans-retinoic acid (Selective) [ 96 ], retinol (Selective) [ 96 ] Comment Forms a heterodimer with TR4; gene disruption appears without effect on testicular development or function...”
• A chemogenomics based approach for deorphanization of testicular receptor 4: An orphan receptor of nuclear receptor superfamily.
  Deshmukh, Journal of natural science, biology, and medicine 2013
  • “...sequence of the testicular receptor 4 (TR4) was retrieved from the SWISS-PROT database with ID P49116. The structure of TR4 was retrieved from RCSB PDB database with ID 3P0U_A. Database homology searching The sequence retrieved was then used to search for sequence homologs against SWISS-PROT database...”
  • “...optimal protein-ligand bound complex. RESULTS AND DISCUSSION The protein sequence retrieved from the SWISS-PROT (ID P49116) was given to BLASTp analysis against SWISS-PROT database. Only those proteins which had >65% identity and had endogenous ligands were taken for further analysis. Overall 10 such receptors were listed...”
• Predictive molecular profiling in blood of healthy vasospastic individuals: clue to targeted prevention as personalised medicine to effective costs.
  Yeghiazaryan, The EPMA journal 2010
  • “...nuclear receptor subfamily 2 group c member 2 (NR2C2); TAK1 U10990 P55092 Orphan Receptors increased P49116 Nuclear Receptors Transcription Activators & Repressors F3a RAR-related orphan receptor C U16997 P51449 Orphan Receptors increased Nuclear Receptors Transcription Activators & Repressors F3e LX receptor alpha (LXR alpha) U22662 Q13133...”
• Vasospastic individuals demonstrate significant similarity to glaucoma patients as revealed by gene expression profiling in circulating leukocytes.
  Yeghiazaryan, Molecular vision 2009
  • “...receptor TR4; nuclear receptor subfamily 2 group c member 2 (NR2C2); TAK1 U10990 P55092 ; P49116 Orphan Receptors; Nuclear Receptors; Transcription Activators & Repressors 3a increased RAR-related orphan receptor C U16997 P51449 Orphan Receptors; Nuclear Receptors; Transcription Activators & Repressors 3e increased LX receptor alpha (LXR...”

NP_001334718 hormone receptor 3, isoform I from Drosophila melanogaster
63% identity, 8% coverage

• The nuclear receptor Hr46/Hr3 is required in the blood brain barrier of mature males for courtship.
  Lama, PLoS genetics 2022
  • GeneRIF: The nuclear receptor Hr46/Hr3 is required in the blood brain barrier of mature males for courtship.
• Early-late genes of the ecdysone cascade as models for transcriptional studies.
  Mazina, Cell cycle (Georgetown, Tex.) 2015
  • GeneRIF: DHR3 and Hr4 gene expression is dose dependent, is completely controlled by the hormone titer and decreases within hours of 20-hydroxyecdysone withdrawal.
• The binding of multiple nuclear receptors to a single regulatory region is important for the proper expression of EDG84A in Drosophila melanogaster.
  Akagi, Journal of molecular biology 2013 (PubMed)
  • GeneRIF: DHR3 and betaFTZ-F1 activate the EDG84A gene in a redundant manner. The temporal expression of the EDG84A gene is mainly controlled by betaFTZ-F1 but that the binding of DHR3 is also important.
• [SAYP interacts with DHR3 nuclear receptor and participates in ecdysone-dependent transcription regulation].
  Vorob'eva, Genetika 2012 (PubMed)
  • GeneRIF: SAYP interacts with DHR3 nuclear receptor and activates the corresponding genes by recruiting the BTFly (Brahma and TFIID) coactivator supercomplex during development and have multiple common targets across the genome.
• SAYP interacts with DHR3 nuclear receptor and participates in ecdysone-dependent transcription regulation.
  Vorobyeva, Cell cycle (Georgetown, Tex.) 2011 (PubMed)
  • GeneRIF: DHR3 and SAYP interact during development and have multiple common targets across the genome
• The Drosophila nuclear receptors DHR3 and betaFTZ-F1 control overlapping developmental responses in late embryos.
  Ruaud, Development (Cambridge, England) 2010
  • GeneRIF: Mid-embryonic expression of DHR3 and betaFTZ-F1 is part of a 20-hydroxyecdysone (20E)-triggered transcriptional cascade, directing maximal expression of E74A and E75A during late embryogenesis.
• The nuclear receptor DHR3 modulates dS6 kinase-dependent growth in Drosophila.
  Montagne, PLoS genetics 2010
  • GeneRIF: DHR3 modulates dS6 kinase-dependent growth in Drosophila.

XP_017149048 probable nuclear hormone receptor HR3 isoform X1 from Drosophila miranda
63% identity, 10% coverage

• Controlling the development of the dengue vector Aedes aegypti using HR3 RNAi transgenic Chlamydomonas
  Fei, PloS one 2020
  • “...Papilio machaon (PmHR3X1, XP_014364014), Papilio polytes (PpHR3X1, XP_013136657), Drosophila biarmipes (DbHR3X1, XP_016947144), Drosophila Miranda (DmHR3X1, XP_017149048), Stomoxys calcitrans (ScHR3X2, XP_013103855), Rhagoletis zephyria (RZHR3X2, XP_017466500), Bactrocera dorsalis (BdHR3X1, XP_019847140), Zeugodacus cucurbitae (ZcHR3X1, XP_011182274), Bactrocera latifrons (BlHR3, XP_018799932), Anopheles sinensis (AsHR3, KFB44899), Aedes albopictus (AalHR3X5, XP_019549827), and Aedes...”
  • “...Papilio machaon (PmHR3X1, XP_014364014), Papilio polytes (PpHR3X1, XP_013136657), Drosophila biarmipes (DbHR3X1, XP_016947144), Drosophila miranda (DmHR3X1, XP_017149048), Stomoxys calcitrans (ScHR3X2, XP_013103855), Rhagoletis zephyria (RZHR3X2, XP_017466500), Bactrocera dorsalis (BdHR3X1, XP_019847140), Zeugodacus cucurbitae (ZcHR3X1, XP_011182274), Bactrocera latifrons (BlHR3, XP_018799932), Anopheles sinensis (AsHR3, KFB44899), Aedes albopictus (AalHR3X5, XP_019549827), and Aedes...”

XP_016947144 probable nuclear hormone receptor HR3 isoform X1 from Drosophila biarmipes
63% identity, 9% coverage

• Controlling the development of the dengue vector Aedes aegypti using HR3 RNAi transgenic Chlamydomonas
  Fei, PloS one 2020
  • “...homologs. Sequences are from Papilio machaon (PmHR3X1, XP_014364014), Papilio polytes (PpHR3X1, XP_013136657), Drosophila biarmipes (DbHR3X1, XP_016947144), Drosophila Miranda (DmHR3X1, XP_017149048), Stomoxys calcitrans (ScHR3X2, XP_013103855), Rhagoletis zephyria (RZHR3X2, XP_017466500), Bactrocera dorsalis (BdHR3X1, XP_019847140), Zeugodacus cucurbitae (ZcHR3X1, XP_011182274), Bactrocera latifrons (BlHR3, XP_018799932), Anopheles sinensis (AsHR3, KFB44899), Aedes albopictus...”
  • “...Protein sequences are from Papilio machaon (PmHR3X1, XP_014364014), Papilio polytes (PpHR3X1, XP_013136657), Drosophila biarmipes (DbHR3X1, XP_016947144), Drosophila miranda (DmHR3X1, XP_017149048), Stomoxys calcitrans (ScHR3X2, XP_013103855), Rhagoletis zephyria (RZHR3X2, XP_017466500), Bactrocera dorsalis (BdHR3X1, XP_019847140), Zeugodacus cucurbitae (ZcHR3X1, XP_011182274), Bactrocera latifrons (BlHR3, XP_018799932), Anopheles sinensis (AsHR3, KFB44899), Aedes albopictus...”

XP_011182274 mucin-5AC isoform X1 from Zeugodacus cucurbitae
63% identity, 8% coverage

• Controlling the development of the dengue vector Aedes aegypti using HR3 RNAi transgenic Chlamydomonas
  Fei, PloS one 2020
  • “...and Papilio polytes (XP_013136657) . However, the homology was the lowest (71%) with Zeugodacus cucurbitae (XP_011182274) ( Fig 2 ). 10.1371/journal.pone.0240223.g001 Fig 1 Amino acid sequence alignment of Aedes aegypti HR3 with its homologs. Sequences are from Papilio machaon (PmHR3X1, XP_014364014), Papilio polytes (PpHR3X1, XP_013136657), Drosophila...”
  • “...Stomoxys calcitrans (ScHR3X2, XP_013103855), Rhagoletis zephyria (RZHR3X2, XP_017466500), Bactrocera dorsalis (BdHR3X1, XP_019847140), Zeugodacus cucurbitae (ZcHR3X1, XP_011182274), Bactrocera latifrons (BlHR3, XP_018799932), Anopheles sinensis (AsHR3, KFB44899), Aedes albopictus (AalHR3X5, XP_019549827), and Aedes aegypti (AaHR3, AF230281, AAEL009588-PA). The DNA-binding domain (C domain), hinge region (D domain), and ligand-binding domain...”

NR2C2_MOUSE / P49117 Nuclear receptor subfamily 2 group C member 2; Orphan nuclear receptor TAK1; Orphan nuclear receptor TR4; Testicular receptor 4 from Mus musculus (Mouse) (see 8 papers)
NP_035760 nuclear receptor subfamily 2 group C member 2 isoform 2 from Mus musculus
61% identity, 12% coverage

• function: Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Activates transcriptional activity of LHCG and is antagonist of PPARA- mediated transactivation (By similarity). Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'- AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior.
  subunit: Homodimer; can bind DNA as homodimer (By similarity). Heterodimer; binds DNA as a heterodimer with NR2C1 required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with NR2C2AP; the interaction represses selective NR2C2-mediated transcriptional activity (By similarity). Interacts with PCAF; the interaction preferentially occurs on the non- phosphorylated form and induces NR2C2-mediated transactivation activity and does not require the ligand-binding domain (PubMed:16887930). Interacts (MAPK-mediated phosphorylated form) with NRIP1; the interaction promotes repression of NR2C2-mediated activity (PubMed:16887930). Interacts with NLRP10. Interacts (via ligand-binding region) with transcriptional corepressor JAZF1; the interaction promotes NR2C2-mediated transcriptional repression (By similarity).
  disruption phenotype: Impaired spermatogenesis. Mutant animals have smaller cerebellums with disruption of lobes VI-VII. They exhibit a delay in monolayer maturation of dysmorphic calbindin 28K-positive Purkinje cells 7 days after birth. Deficiencies in acoustic startle response, prepulse startle inhibition, and social interactions were observed. Also responses to novel environmental situations are inhibited. NR2C1 and NR2C2 double knockout results in embryonic lethality around 7.5 dpc and increased apoptosis.
• Mycobacterium tuberculosis Rv1043c regulates the inflammatory response by inhibiting the phosphorylation of TAK1.
  Li, International microbiology : the official journal of the Spanish Society for Microbiology 2024 (PubMed)
  • GeneRIF: Mycobacterium tuberculosis Rv1043c regulates the inflammatory response by inhibiting the phosphorylation of TAK1.
• TR4 worsen urosepsis by regulating GSDMD.
  Wang, European journal of medical research 2024
  • GeneRIF: TR4 worsen urosepsis by regulating GSDMD.
• Roquin-2 promotes oxidative stress-induced cell death by ubiquitination-dependent degradation of TAK1.
  Hirata, Free radical biology & medicine 2024 (PubMed)
  • GeneRIF: Roquin-2 promotes oxidative stress-induced cell death by ubiquitination-dependent degradation of TAK1.
• Disruption of TIGAR-TAK1 alleviates immunopathology in a murine model of sepsis.
  Wang, Nature communications 2024
  • GeneRIF: Disruption of TIGAR-TAK1 alleviates immunopathology in a murine model of sepsis.
• Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Mediates Chronic Pain and Cytokine Production in Mouse Models of Inflammatory, Neuropathic, and Primary Pain.
  Scarneo, The journal of pain 2023
  • GeneRIF: Transforming Growth Factor-beta-Activated Kinase 1 (TAK1) Mediates Chronic Pain and Cytokine Production in Mouse Models of Inflammatory, Neuropathic, and Primary Pain.
• Small molecule activators of TAK1 promotes its activity-dependent ubiquitination and TRAIL-mediated tumor cell death.
  Sun, Proceedings of the National Academy of Sciences of the United States of America 2023
  • GeneRIF: Small molecule activators of TAK1 promotes its activity-dependent ubiquitination and TRAIL-mediated tumor cell death.
• TAK1 is an essential kinase for STING trafficking.
  Ma, Molecular cell 2023 (PubMed)
  • GeneRIF: TAK1 is an essential kinase for STING trafficking.
• TAK1 is essential for endothelial barrier maintenance and repair after lung vascular injury.
  Wang, Molecular biology of the cell 2022
  • GeneRIF: TAK1 is essential for endothelial barrier maintenance and repair after lung vascular injury.
• More

NP_059019 nuclear receptor subfamily 2 group C member 2 from Rattus norvegicus
61% identity, 12% coverage

• Loss of TR4 orphan nuclear receptor reduces phosphoenolpyruvate carboxykinase-mediated gluconeogenesis.
  Liu, Diabetes 2007 (PubMed)
  • GeneRIF: Both in vitro and in vivo data demonstrate the identification of a new pathway, TR4---> phosphoenolpyruvate carboxykinase--->gluconeogenesis--->blood glucose.
• Stage dependent and androgen inductive expression of orphan receptor TR4 in rat testis.
  Mu, Biochemical and biophysical research communications 2006 (PubMed)
  • GeneRIF: expression of TR4 in rat testis is stage dependent and androgen inductive, and TR4 may have an important role in spermatogenesis
• Induction of apolipoprotein E expression by TR4 orphan nuclear receptor via 5' proximal promoter region.
  Kim, Biochemical and biophysical research communications 2005 (PubMed)
  • GeneRIF: Together, our data demonstrate that TR4 can enhance apoE gene expression via binding to TR4RE-DR0 in apoE 5' promoter and this TR4 binding is essential for synergistic interaction with another transcription factor, Sp1.
• Modulation of the retinoic acid-induced cell apoptosis and differentiation by the human TR4 orphan nuclear receptor.
  Lee, Biochemical and biophysical research communications 2004 (PubMed)
  • GeneRIF: Together, these findings provide the first in vivo evidence that an orphan nuclear receptor, such as TR4, may play major roles in the RA-mediated apoptosis or differentiation in P19 cells.
• Testicular orphan receptor 4 induced hepatic stellate cells activation via the regulation of TGF-β receptor Ⅰ/Smad2/3 signaling pathway.
  Fu, Annals of hepatology (PubMed)
  • GeneRIF: Testicular orphan receptor 4 induced hepatic stellate cells activation via the regulation of TGF-beta receptor /Smad2/3 signaling pathway.

NR2C2_RAT / P55094 Nuclear receptor subfamily 2 group C member 2; Orphan nuclear receptor TR4; Testicular receptor 4 from Rattus norvegicus (Rat) (see 2 papers)
61% identity, 12% coverage

• function: Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Activates transcriptional activity of LHCG and is antagonist of PPARA- mediated transactivation. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior (By similarity).
  subunit: Homodimer; can bind DNA as homodimer. Heterodimer; binds DNA as a heterodimer with NR2C1 required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with NR2C2AP; the interaction represses selective NR2C2-mediated transcriptional activity. Interacts with PCAF; the interaction preferentially occurs on the non-phosphorylated form and induces NR2C2- mediated transactivation activity and does not require the ligand- binding domain. Interacts (MAPK-mediated phosphorylated form) with NRIP1; the interaction promotes repression of NR2C2-mediated activity. Interacts with NLRP10. Interacts (via ligand-binding region) with transcriptional corepressor JAZF1; the interaction promotes NR2C2- mediated transcriptional repression.

XP_015145732 retinoic acid receptor RXR-gamma isoform X1 from Gallus gallus
58% identity, 13% coverage

• RXRG associated in PPAR signal regulated the differentiation of primordial germ cell.
  Cheng, Journal of cellular biochemistry 2018 (PubMed)
  • GeneRIF: The results showed that the expression of FABP3 and SCD-1 was up-regulated by high expression of RXRG, which significantly up-regulated the expression of Cvh, C-kit, and the ratio of Cvh + C-kit+ cells was higher than that of control group.

XP_008189754 probable nuclear hormone receptor HR3 isoform X3 from Acyrthosiphon pisum
64% identity, 10% coverage

• Role of nuclear receptors NlHR3 and NlFTZ-F1 in regulating molting and reproduction in Nilaparvata lugens (stål)
  Li, Frontiers in physiology 2023
  • “...Acyrthosiphon pisum , XP_003240875), ApHR3X2 ( Acyrthosiphon pisum , XP_008189753), ApHR3X3 ( Acyrthosiphon pisum , XP_008189754), ApHR3X4 ( Acyrthosiphon pisum , XP_008189756), BmHR3 ( Bombyx mori , NP_001037012), BmHR3X1 ( Bombyx mori , XP_012551821), NvHR3 ( Nasonia vitripennis , XP_008202385), TcHR3X1 ( Tribolium castaneum , XP_974561),...”

NP_788301 hormone receptor 3, isoform C from Drosophila melanogaster
63% identity, 11% coverage

• Identification and temporal expression of putative circadian clock transcripts in the amphipod crustacean Talitrus saltator
  O'Grady, PeerJ 2016
  • “...VRILLE AAF52237 comp100474_c0_seq6 3,949 Tal-VRI Full 509 EBONY AAF55870 comp99283_c0_seq2 4,380 Tal-EBONY Full 974 RORA NP_788301 comp99654_c0_seq3 2,217 Tal-RORA Partial 599 REVERB NP_730321 comp101252_c0_seq2 5,385 Tal-REVERB Full 1,110 SIRT1 NP_477351 comp101818_c1_seq1 4,033 Tal-SIRT1 Partial 955 SIRT2 NP_650880 comp97450_c0_seq4 2,275 Tal-SIRT2 Partial 376 SIRT4 NP_572241 comp92313_c0_seq2 2,977...”
  • “...Figure S19 Putative Talitrus saltator RORA protein Alignment of Drosophila melanogaster RORA (Drome-RORA; Accession No. NP_788301 ) with the T. saltator RORA (Tal-RORA) deduced from the Trinity de novo transcriptome assembly, together with the top two tblastn species homologue sequences Drosophila grimshawi RORA (Drogr-RORA; Accession No....”

Smp_000340 nuclear hormone receptor superfamily protein-related from Schistosoma mansoni
67% identity, 7% coverage

• Schistosoma mansoni Egg, Adult Male and Female Comparative Gene Expression Analysis and Identification of Novel Genes by RNA-Seq
  Anderson, PLoS neglected tropical diseases 2015
  • “...from transcription and translation to mRNA decay [ 57 ]. The nuclear receptor SmE78 gene (Smp_000340) also showed an increased expression in eggs. Wu et al. had previously shown that nuclear receptors are important transcriptional modulators, and in S . mansoni , SmE78 may be involved...”

Smp_105090 nuclear hormone receptor,putative from Schistosoma mansoni
63% identity, 5% coverage

• The retinoic acid family-like nuclear receptor SmRAR identified by single-cell transcriptomics of ovarian cells controls oocyte differentiation in Schistosoma mansoni
  Moescheid, Nucleic acids research 2025
  • “...receptors are described that belong to the class of all-trans retinoid acid/opsin-NRs (Smp_073470, Smp_097700, and Smp_105090, Figure 4 ). These paralogs were found to be co-transcribed with Sm rar ( Supplemental Figure S20 ) with highest transcript levels in intermediate-stage oocytes, and lowest levels in mature...”

XP_008189753 probable nuclear hormone receptor HR3 isoform X2 from Acyrthosiphon pisum
64% identity, 9% coverage

• Role of nuclear receptors NlHR3 and NlFTZ-F1 in regulating molting and reproduction in Nilaparvata lugens (stål)
  Li, Frontiers in physiology 2023
  • “...Apis mellifera , XP_006570914), ApHR3X1 ( Acyrthosiphon pisum , XP_003240875), ApHR3X2 ( Acyrthosiphon pisum , XP_008189753), ApHR3X3 ( Acyrthosiphon pisum , XP_008189754), ApHR3X4 ( Acyrthosiphon pisum , XP_008189756), BmHR3 ( Bombyx mori , NP_001037012), BmHR3X1 ( Bombyx mori , XP_012551821), NvHR3 ( Nasonia vitripennis , XP_008202385),...”

N2C1A_XENLA / Q6GN21 Nuclear receptor subfamily 2 group C member 1-A; Developmental orphan receptor 2-A; DOR2-A; xDOR2-A; Orphan nuclear receptor TR2-A; Testicular receptor 2-A from Xenopus laevis (African clawed frog) (see paper)
65% identity, 11% coverage

• function: Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences (By similarity).

XP_008189756 probable nuclear hormone receptor HR3 isoform X5 from Acyrthosiphon pisum
64% identity, 11% coverage

• Role of nuclear receptors NlHR3 and NlFTZ-F1 in regulating molting and reproduction in Nilaparvata lugens (stål)
  Li, Frontiers in physiology 2023
  • “...Acyrthosiphon pisum , XP_008189753), ApHR3X3 ( Acyrthosiphon pisum , XP_008189754), ApHR3X4 ( Acyrthosiphon pisum , XP_008189756), BmHR3 ( Bombyx mori , NP_001037012), BmHR3X1 ( Bombyx mori , XP_012551821), NvHR3 ( Nasonia vitripennis , XP_008202385), TcHR3X1 ( Tribolium castaneum , XP_974561), TcHR3X2 ( Tribolium castaneum , XP_008195824),...”

Q6P3U7 Retinoic acid receptor RXR (Fragment) from Homo sapiens
57% identity, 14% coverage

• Deciphering the Underlying Mechanism of Eucommiae Cortex against Osteoporotic Fracture by Network Pharmacology.
  Shuai, Evidence-based complementary and alternative medicine : eCAM 2020
  • “...P04150 NR3C1 Nuclear receptor subfamily 3 group C member 1 23 P02768 ALB Albumin 22 Q6P3U7 RXRA Retinoid X receptor alpha 21 P22681 CBL Cbl proto-oncogene 21 P01308 INS Insulin 20 P17612 PRKACA Protein kinase cAMP-activated catalytic subunit alpha 18 P02765 AHSG Alpha 2-HS glycoprotein 18...”
• Quantitative proteomic analyses of influenza virus-infected cultured human lung cells.
  Coombs, Journal of virology 2010

XP_003240875 probable nuclear hormone receptor HR3 isoform X1 from Acyrthosiphon pisum
64% identity, 9% coverage

• Role of nuclear receptors NlHR3 and NlFTZ-F1 in regulating molting and reproduction in Nilaparvata lugens (stål)
  Li, Frontiers in physiology 2023
  • “...Anopheles gambiae , EAA14853), AmHR3 ( Apis mellifera , XP_006570914), ApHR3X1 ( Acyrthosiphon pisum , XP_003240875), ApHR3X2 ( Acyrthosiphon pisum , XP_008189753), ApHR3X3 ( Acyrthosiphon pisum , XP_008189754), ApHR3X4 ( Acyrthosiphon pisum , XP_008189756), BmHR3 ( Bombyx mori , NP_001037012), BmHR3X1 ( Bombyx mori , XP_012551821),...”

RXRG_CHICK / P28701 Retinoic acid receptor RXR-gamma; Nuclear receptor subfamily 2 group B member 3; Retinoid X receptor gamma from Gallus gallus (Chicken) (see 2 papers)
58% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity).
  subunit: Homodimer. Heterodimer; with a RAR molecule. Binds DNA preferentially as a RAR/RXR heterodimer.

RXRG_RAT / Q5BJR8 Retinoic acid receptor RXR-gamma; Nuclear receptor subfamily 2 group B member 3; Retinoid X receptor gamma from Rattus norvegicus (Rat) (see 2 papers)
NP_113953 retinoic acid receptor RXR-gamma from Rattus norvegicus
58% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity).
  subunit: Homodimer (By similarity). Heterodimer with a RAR molecule (By similarity). Binds DNA preferentially as a RAR/RXR heterodimer (By similarity). Interacts with RARA (By similarity).
• miR‑330‑5p inhibits H2O2‑induced adipogenic differentiation of MSCs by regulating RXRγ.
  Huang, International journal of molecular medicine 2018
  • GeneRIF: the results of the present study revealed that miR3305p acts as a critical regulator of RXRgamma, and is able to determinate the fate of MSCs to differentiate into adipocytes. This suggests that miR3305p and RXRgamma may be target molecules for controlling metabolic diseases.
• Expression of retinoic acid receptors and retinoid X receptors in normal and vitamin A deficient adult rat brain.
  Arfaoui, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 2013 (PubMed)
  • GeneRIF: RXRgamma was absent in the female rat brain, while it was observed in some regions in the male.
• Hypoxia-inducible factor 1 mediates hypoxia-induced cardiomyocyte lipid accumulation by reducing the DNA binding activity of peroxisome proliferator-activated receptor alpha/retinoid X receptor.
  Belanger, Biochemical and biophysical research communications 2007 (PubMed)
  • GeneRIF: These results suggest that HIF-1 may be involved in hypoxia-induced suppression of fatty acid metabolism in cardiomyocytes by reducing the DNA binding activity of PPARalpha/RXR.
• Peroxisome proliferator-activated receptor alpha (PPARalpha) potentiates, whereas PPARgamma attenuates, glucose-stimulated insulin secretion in pancreatic beta-cells.
  Ravnskjaer, Endocrinology 2005 (PubMed)
  • GeneRIF: Ectopic expression of PPARgamma/RXRalpha increases fatty acid uptake and deposition as triacylglycerides.

XP_021186797 probable nuclear hormone receptor HR3 isoform X6 from Helicoverpa armigera
63% identity, 11% coverage

• Transgenic Cotton Plants Expressing the HaHR3 Gene Conferred Enhanced Resistance to Helicoverpa armigera and Improved Cotton Yield.
  Han, International journal of molecular sciences 2017
  • GeneRIF: Transgenic cotton plants expressing dsHaHR3 were shown to induce high larval mortality and deformities of pupation and adult eclosion when used to feed the newly hatched larvae, and 3rd and 5th instar larvae of H. armigera

Q0GFF6 Retinoic acid receptor RXR-gamma from Sus scrofa
58% identity, 16% coverage

• Composition and physiological functions of the porcine colostrum.
  Inoue, Animal science journal = Nihon chikusan Gakkaiho 2021
  • “...Prolyl endopeptidase 19 Q2EN75 Protein S100A6 0.4 33 Q7YS91 Protein TBRG4 25 P26044 Radixin 42 Q0GFF6 Retinoic acid receptor RXRgamma 19 Q06AT9 RNAbinding protein 4B 19 Q3YLA6 Serine/argininerich splicing factor 1 28 P61292 Serine/threonineprotein phosphatase PP1beta catalytic subunit 22 D2WKD8 Sodium/potassiumtransporting ATPase subunit alpha2 0.03 37...”

RXRG_MOUSE / P28705 Retinoic acid receptor RXR-gamma; Nuclear receptor subfamily 2 group B member 3; Retinoid X receptor gamma from Mus musculus (Mouse) (see 2 papers)
NP_033133 retinoic acid receptor RXR-gamma isoform 1 from Mus musculus
58% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity).
  subunit: Homodimer (By similarity). Heterodimer with a RAR molecule (By similarity). Binds DNA preferentially as a RAR/RXR heterodimer (By similarity). Interacts with RARA (By similarity).
  disruption phenotype: Knockout mice exhibit memory deficits.
• RXRγ attenuates cerebral ischemia-reperfusion induced ferroptosis in neurons in mice through transcriptionally promoting the expression of GPX4.
  Yang, Metabolic brain disease 2022 (PubMed)
  • GeneRIF: RXRgamma attenuates cerebral ischemia-reperfusion induced ferroptosis in neurons in mice through transcriptionally promoting the expression of GPX4.
• Loss of retinoid X receptor gamma subunit impairs group 1 mGluR mediated electrophysiological responses and group 1 mGluR dependent behaviors.
  Upreti, Scientific reports 2021
  • GeneRIF: Loss of retinoid X receptor gamma subunit impairs group 1 mGluR mediated electrophysiological responses and group 1 mGluR dependent behaviors.
• Regulation of retinoid X receptor gamma expression by fed state in mouse liver.
  Park, Biochemical and biophysical research communications 2015 (PubMed)
  • GeneRIF: RXR-gamma plays an important role in tight control of glucose metabolism in the fasting-feeding cycle.The regulation of RXR-gamma expression in the liver by feeding or glucose.
• Clobetasol and Halcinonide Act as Smoothened Agonists to Promote Myelin Gene Expression and RxRγ Receptor Activation.
  Porcu, PloS one 2015
  • GeneRIF: Data show that halcinonide and clobetasol act as Smoothened (Smo) agonists to up-regulate myelin gene expression and retinoid X receptor gamma (RxRgamma) activation.
• Retinoid receptors trigger neuritogenesis in retinal degenerations.
  Lin, FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2012
  • GeneRIF: Using the light-induced retinal degeneration (LIRD) mouse model, which provides a unique platform for exploring the mechanisms underlying neuritogenesis, we found that retinoid X receptors (RXRs) control neuritogenesis.
• Retinoid x receptor gamma control of affective behaviors involves dopaminergic signaling in mice.
  Krzyzosiak, Neuron 2010 (PubMed)
  • GeneRIF: The data of this study argued that control of NAc dopamine d2 receptor expression is critical for Retinoid x receptor gamma-mediated modulation of affective behaviors.
• Regulation of SREBP1c gene expression in skeletal muscle: role of retinoid X receptor/liver X receptor and forkhead-O1 transcription factor.
  Kamei, Endocrinology 2008 (PubMed)
  • GeneRIF: RXR/LXR up-regulates SREBP1c gene expression and FOXO1 antagonizes this effect of RXR/LXR in skeletal muscle.
• Prepubertal testis development relies on retinoic acid but not rexinoid receptors in Sertoli cells.
  Vernet, The EMBO journal 2006
  • GeneRIF: The ablation of all RXR (alpha, beta and gamma isotypes) in Sertoli cells does not recapitulate the phenotype generated upon ablation of all three retinoic acid receptors.

RXRG_HUMAN / P48443 Retinoic acid receptor RXR-gamma; Nuclear receptor subfamily 2 group B member 3; Retinoid X receptor gamma from Homo sapiens (Human) (see 2 papers)
NP_008848 retinoic acid receptor RXR-gamma isoform a from Homo sapiens
58% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity).
  subunit: Homodimer (By similarity). Heterodimer with a RAR molecule (PubMed:28167758). Binds DNA preferentially as a RAR/RXR heterodimer (PubMed:28167758). Interacts with RARA (PubMed:28167758).
• Association between functional genetic variants in retinoid X receptor-α/γ and the risk of gestational diabetes mellitus in a southern Chinese population.
  Yu, Bioscience reports 2021
  • GeneRIF: Association between functional genetic variants in retinoid X receptor-alpha/gamma and the risk of gestational diabetes mellitus in a southern Chinese population.
• Association between Single-nucleotide Polymorphisms of RXRG and Genetic Susceptibility to Type 2 Diabetes in South China.
  Yu, Current molecular medicine 2020 (PubMed)
  • GeneRIF: Association between Single-nucleotide Polymorphisms of RXRG and Genetic Susceptibility to Type 2 Diabetes in South China.
• Proteomics to Predict Loss of RXR-γ During Progression of Epithelial Ovarian Cancer.
  Kalra, Methods in molecular biology (Clifton, N.J.) 2019 (PubMed)
  • GeneRIF: Using a progression model of epithelial ovarian cancer (EOC), a proteomics-based approach identified a specific loss of RXR-gamma driving the progression of EOC.
• Whole-exome identifies RXRG and TH germline variants in familial isolated prolactinoma.
  Melo, Cancer genetics 2016 (PubMed)
  • GeneRIF: Germline mutations in the RXRG gene are linked to Familial isolated pituitary adenoma in a Brazilian Family.
• Genetic variants in vitamin D signaling pathways and risk of gestational diabetes mellitus.
  Shi, Oncotarget 2016
  • GeneRIF: Findings indicate that Gc globulin (GC) rs16847024, retinoid X receptor gamma (RXRG) rs17429130 and retinoid X receptor alpha (RXRA) rs4917356 were candidate susceptibility markers for gestational diabetes mellitus (GDM) in Chinese females.
• A vitamin D pathway gene-gene interaction affects low-density lipoprotein cholesterol levels.
  Grave, The Journal of nutritional biochemistry 2016 (PubMed)
  • GeneRIF: genetic association studies in a population in Brazil: Data suggest that SNPs in RXRG (rs2134095) and GC (rs7041) are associated with low-density lipoprotein cholesterol levels and hypercholesterolemia in the population studied; there was no apparent association with an SNP in VDR (rs2228570). (RXRG = retinoid X receptor gamma; GC = vitamin D-binding protein; VDR = vitamin D receptor)
• Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer-specific bioluminescence resonance energy transfer-based sensors.
  Giner, FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2015
  • GeneRIF: Data show that some rexinoids display selective coactivator (CoA) recruitment by the retinoid X receptors (RXRs) homodimer and by the heterodimers nuclear receptor Nur77/RXR and Nurr1/RXR.
• Pregnane X Receptor Expression in Human Pancreatic Adenocarcinoma: Associations With Clinicopathologic Parameters, Tumor Proliferative Capacity, Patients' Survival, and Retinoid X Receptor Expression.
  Koutsounas, Pancreas 2015 (PubMed)
  • GeneRIF: Data show that pregnane X receptor/retinoid X receptor PXR/RXR-[alpha], RXR-[beta], or RXR-[gamma] expression was noted in 9 (16.4%), 9 (16.4%), and 10 (18.2%) pancreatic adenocarcinoma cases, respectively.
• More
• Mechanistic Insights Into <i>Ganoderma Lucidum</i> for Diabetes Treatment via Network Pharmacology and Validation
  Guo, Diabetes, metabolic syndrome and obesity : targets and therapy 2025 (no snippet)
• Retinoid X receptor heterodimers in hepatic function: structural insights and therapeutic potential
  Xu, Frontiers in pharmacology 2024
  • “...in intracellular lipid homeostasis and inflammatory regulation. 2.3 RXR The gene of RXR (UniProt ID: P48443) is located on human chromosome 1q23.3. The RXR protein contains 463 amino acids with a molecular weight of approximately 51kDa. RXR is predominantly found in the pituitary gland, brain, and...”
• FMCA-DTI: a fragment-oriented method based on a multihead cross attention mechanism to improve drug-target interaction prediction.
  Zhang, Bioinformatics (Oxford, England) 2024
  • “...P05177 True True P18089 True True P35462 True True P21728 True True Accuracy 90.9% DB00755-Tretinoin P48443 True True P13631 True False P00352 True True P11712 True True P04798 True True P08684 True True P24462 True True P33260 True True P10632 True True P28702 True True Accuracy...”
• Proteomic analysis reveals changes in the proteome of human THP-1 macrophages infected with Paracoccidioides brasiliensis
  de, Frontiers in cellular and infection microbiology 2023
  • “...* P19793 Retinoic acid receptor RXR-alpha 654.98 * P28702 Retinoic acid receptor RXR-beta 1177.33 * P48443 Retinoic acid receptor RXR-gamma 630.23 * H0Y858 Toll-like receptor 9 (Fragment) 624.89 * A0A499FJK2 Transforming growth factor beta 618.77 * 1 Accession number of matched protein from Homo sapiens macrophages...”
• Drug-target interaction prediction based on spatial consistency constraint and graph convolutional autoencoder.
  Chen, BMC bioinformatics 2023
  • “...9 DB00809 Tropicamide P08912 CHRM5 STITCH 10 DB00734 Risperidone P28222 HTR1B KEGG 11 DB00799 Tazarotene P48443 RXRG KEGG 12 DB06216 Asenapine P21918 DRD5 DrugCentral 13 DB00543 Amoxapine P28223 HTR2A DrugBank 14 DB01186 Pergolide P34969 HTR7 STITCH 15 DB00411 Carbachol P20309 CHRM3 DrugBank 16 DB00806 Pentoxifylline Q08499...”
• Clustering Protein Binding Pockets and Identifying Potential Drug Interactions: A Novel Ligand-Based Featurization Method.
  Stevenson, Journal of chemical information and modeling 2023
  • “...Also in cluster #140 are pockets on UniProt IDs P19793 (retinoic acid receptor RXR-alpha) and P48443 (retinoic acid receptor RXR-gamma). While our initial knowledge of interactions shows molecule D having activity only against Q03181 , PubChem bioassay results indicate that molecule D has activity against RARA...”
• Study on the Mechanism of Improving HIV/AIDS Immune Function with Jian Aikang Concentrated Pill Based on Network Pharmacology Combined with Experimental Validation
  Shao, Drug design, development and therapy 2022
  • “...P12004 134 SLC6A3 Q01959 30 CDK1 P06493 65 FLT1 P17948 100 NR3C2 P08235 135 RXRG P48443 31 CDH1 P12830 66 FGFR1 P11362 101 MMP7 P09237 136 RB1 P06400 32 CCNA2 P20248 67 FASN P49327 102 MMP1 P03956 137 PTEN P60484 33 BRAF P15056 68 F3 P13726...”
• Network Pharmacology Analyses of the Pharmacological Targets and Therapeutic Mechanisms of Salvianolic Acid A in Myocardial Infarction
  Huang, Evidence-based complementary and alternative medicine : eCAM 2022
  • “...APH-1B P62942 Peptidyl-prolyl cis-trans isomerase FKBP1A Q8TDS4 Hydroxycarboxylic acid receptor 2 P51639 3-Hydroxy-3-methylglutaryl-coenzyme A reductase P48443 Retinoic acid receptor RXR-gamma O14842 Free fatty acid receptor 1 Q92542 Nicastrin P41231 P2Y purinoceptor 2 P31639 Sodium/glucose cotransporter 2 P00491 Purine nucleoside phosphorylase P55157 Microsomal triglyceride transfer protein large...”
• More

Q3ZAR9 Nr2c2 protein from Mus musculus
61% identity, 15% coverage

• ITRAQ-based quantitative proteomic analysis of processed Euphorbia lathyris L. for reducing the intestinal toxicity.
  Zhang, Proteome science 2018
  • “...Gm5576 1 1.3237 1.14 1.2215 P15119 Mast cell protease 2 Mcpt2 1 1.322 1.36 1.0482 Q3ZAR9 Nr2c2 protein (Nuclear receptor subfamily 2 group C member 2) Nr2c2 1 1.3202 1.395 1.158 Q8BSI6 R3H and coiled-coil domain-containing protein 1 R3hcc1 1 1.319 1.279 1.569 Q32M212 Gasdermin-A2 Gsdma2...”

XP_013136657 probable nuclear hormone receptor HR3 isoform X1 from Papilio polytes
63% identity, 13% coverage

• Controlling the development of the dengue vector Aedes aegypti using HR3 RNAi transgenic Chlamydomonas
  Fei, PloS one 2020
  • “...(XP_019549827) , followed by Anopheles sinensis (KFB44899) , Papilio machaon (XP_014364014) , and Papilio polytes (XP_013136657) . However, the homology was the lowest (71%) with Zeugodacus cucurbitae (XP_011182274) ( Fig 2 ). 10.1371/journal.pone.0240223.g001 Fig 1 Amino acid sequence alignment of Aedes aegypti HR3 with its homologs....”
  • “...HR3 with its homologs. Protein sequences are from Papilio machaon (PmHR3X1, XP_014364014), Papilio polytes (PpHR3X1, XP_013136657), Drosophila biarmipes (DbHR3X1, XP_016947144), Drosophila miranda (DmHR3X1, XP_017149048), Stomoxys calcitrans (ScHR3X2, XP_013103855), Rhagoletis zephyria (RZHR3X2, XP_017466500), Bactrocera dorsalis (BdHR3X1, XP_019847140), Zeugodacus cucurbitae (ZcHR3X1, XP_011182274), Bactrocera latifrons (BlHR3, XP_018799932), Anopheles sinensis...”

RXRA_MOUSE / P28700 Retinoic acid receptor RXR-alpha; Nuclear receptor subfamily 2 group B member 1; Retinoid X receptor alpha from Mus musculus (Mouse) (see 12 papers)
57% identity, 16% coverage

• function: Receptor for retinoic acid that acts as a transcription factor (PubMed:10383391, PubMed:12032153, PubMed:25417649). Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9- cis retinoic acid, to regulate gene expression in various biological processes (PubMed:10383391, PubMed:1310259). The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (PubMed:1310259). The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:10383391, PubMed:25417649). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (By similarity). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (By similarity). Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (PubMed:1310259). The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (By similarity). The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (By similarity). Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (By similarity). Acts as an enhancer of RARA binding to RARE DNA element (By similarity). May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (By similarity). Promotes myelin debris phagocytosis and remyelination by macrophages (PubMed:26463675). Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes (PubMed:25417649). Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (By similarity).
  subunit: Homodimer (By similarity). Heterodimer with RARA; required for ligand-dependent retinoic acid receptor transcriptional activity (PubMed:10882070). Heterodimer with PPARA (via the leucine-like zipper in the LBD); the interaction is required for PPARA transcriptional activity (By similarity). Heterodimerizes with PPARG (PubMed:7838715). Heterodimerizes (via NR LBD) with RARB (By similarity). Heterodimerizes with NR1H4; the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators (By similarity). Interacts with coactivator NCO6 (PubMed:10788465). Interacts with coactivator NCO3 (By similarity). Interacts with coactivator FAM120B (PubMed:17595322). Interacts with coactivator PELP1, SENP6, SFPQ, DNTTIP2 and RNF8 (By similarity). Interacts with PRMT2 (By similarity). Interacts with ASXL1 (PubMed:16606617). Interacts with BHLHE40/DEC1, BHLHE41/DEC2, NCOR1 and NCOR2 (By similarity). Interacts in a ligand-dependent fashion with MED1 and NCOA1 (PubMed:15528208, PubMed:16606617). Interacts with VDR (By similarity). Interacts with EP300; the interaction is decreased by 9-cis retinoic acid (By similarity). Heterodimer (via C-terminus) with NR4A1 (via DNA-binding domain); the interaction is enhanced by 9-cis retinoic acid (By similarity). NR4A1 competes with EP300 for interaction with RXRA and thereby attenuates EP300 mediated acetylation of RXRA (By similarity). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863). Interacts ith IGFBP3 (By similarity).
  disruption phenotype: Reduced myelin debris uptake by bone marrow- derived macrophages (PubMed:26463675). Conditional knockout in myeloid cells results in reduced myelin debris clearing by macrophages, delayed oligodendrocyte progenitor cell differentiation and slowern remyelination after induced focal demyelination (PubMed:26463675).
• In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury.
  Li, International journal of molecular sciences 2015
  • “...receptor RXR- MDR1_MOUSE_10000 P06795 MDR3_MOUSE_10000 P21440 HES1_MOUSE_10000 P35428 DYR1A_MOUSE_10000 Q61214 EGFR_MOUSE_10000 Q01279 CAH15_MOUSE_10000 Q99N23 RXRA_MOUSE_1000 P28700 10 Methyl 4-hydroxyphenylacetate ZINC00395674 ACE_MOUSE_1000 P09470 Angiotensin-converting enzyme; Solute carrier family 22 member 20; Solute carrier family 22 member 6; Platelet-derived growth factor receptor (PDGFR); Carbonic anhydrase 15; Mu-type opioid...”
• Exploring the "dark matter" of a mammalian proteome by protein structure and function modeling.
  Brylinski, Proteome science 2013
  • “...Esr1 Estrogen receptor 5 ENSMUSP00000067266 115 P18911 Rarg Retinoic acid receptor gamma 6 ENSMUSP00000076491 114 P28700 Rxva Retinoic acid receptor RXR-alpha 7 ENSMUSP00000106051 114 O08537 Esr2 Estrogen receptor beta 8 ENSMUSP00000027649 113 P45448 Nr5a2 Nuclear receptor subfamily 5 group A member 2 9 ENSMUSP00000053092 108 Q60641...”
• Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases.
  Bogoyevitch, Microbiology and molecular biology reviews : MMBR 2006

NP_036937 retinoic acid receptor RXR-alpha from Rattus norvegicus
57% identity, 16% coverage

• RXRα Blocks Nerve Regeneration after Spinal Cord Injury by Targeting p66shc.
  Yu, Oxidative medicine and cellular longevity 2021
  • GeneRIF: RXRalpha Blocks Nerve Regeneration after Spinal Cord Injury by Targeting p66shc.
• RXRα and MRTF-A have a synergistic effect in the retinoic acid-induced neural-like differentiation of adult bone marrow-derived mesenchymal stem cells.
  Luo, Cell biology international 2020 (PubMed)
  • GeneRIF: RXRalpha and MRTF-A have a synergistic effect in the retinoic acid-induced neural-like differentiation of adult bone marrow-derived mesenchymal stem cells.
• Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization.
  Mukwaya, Angiogenesis 2018
  • GeneRIF: A complex and coordinated time-dependent interplay between pro- and anti-inflammatory signaling pathways highlights a potential anti-inflammatory role of LXR/RXR, PPARalpha/RXRalpha and STAT3 signaling pathways in resolving inflammatory corneal angiogenesis.
• Fundamental studies of adrenal retinoid-X-receptor: Protein isoform, tissue expression, subcellular distribution, and ligand availability.
  Cheng, The Journal of steroid biochemistry and molecular biology 2017 (PubMed)
  • GeneRIF: Data suggest cells of the adrenal gland that contain RXRalpha are primarily localized in zona fasciculata and adrenal medulla with RXRalpha almost exclusively localized in cell nucleus; cells that contain RXRbeta are primarily localized in zona fasciculata. RXR ligands, such as all-trans-retinoic acid and long-chain polyunsaturated fatty acids, are also present in the adrenal gland.
• Contribution of PPARα/β/γ, AP-1, importin-α3, and RXRα to the protective effect of 5,14-HEDGE, a 20-HETE mimetic, against hypotension, tachycardia, and inflammation in a rat model of septic shock.
  Senol, Inflammation research : official journal of the European Histamine Research Society ... [et al.] 2016 (PubMed)
  • GeneRIF: The results suggest that an increase in the expression of PPARalpha/beta/gamma and RXRalpha as well as a decrease in AP-1 and importin-alpha3 expression/activity participates in the protective effect of 5,14-HEDGE against hypotension, tachycardia, and inflammation during endotoxemia and thus have a beneficial effect in septic shock treatment
• Expression of retinoic acid receptors and retinoid X receptors in normal and vitamin A deficient adult rat brain.
  Arfaoui, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 2013 (PubMed)
  • GeneRIF: RXRalpha were hardly detected in female brain, but were detected more frequently in male rats.
• Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors.
  German, Journal of lipid research 2013
  • GeneRIF: The results imply that activation of RXRa was required for DHA protection whereas Trk receptors were not involved in this protection.
• High glucose-induced repression of RAR/RXR in cardiomyocytes is mediated through oxidative stress/JNK signaling.
  Singh, Journal of cellular physiology 2012
  • GeneRIF: The impaired RAR/RXR signaling and oxidative stress/JNK pathway forms a vicious circle, which significantly contributes to hyperglycemia induced cardiomyocyte apoptosis.
• More

XP_003642339 retinoic acid receptor RXR-alpha isoform X1 from Gallus gallus
57% identity, 16% coverage

• Cholesterol secretion and homeostasis in chondrocytes: a liver X receptor and retinoid X receptor heterodimer mediates apolipoprotein A1 expression.
  Gentili, Matrix biology : journal of the International Society for Matrix Biology 2005 (PubMed)
  • GeneRIF: liver X receptor and retinoid X receptor heterodimer mediates apolipoprotein A1 expression

RXRA_RAT / Q05343 Retinoic acid receptor RXR-alpha; Nuclear receptor subfamily 2 group B member 1; Retinoid X receptor alpha from Rattus norvegicus (Rat) (see 3 papers)
57% identity, 16% coverage

• function: Receptor for retinoic acid that acts as a transcription factor (By similarity). Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes (By similarity). The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (By similarity). The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (By similarity). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (By similarity). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (By similarity). Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (By similarity). The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (By similarity). The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (PubMed:8381967). Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (By similarity). Acts as an enhancer of RARA binding to RARE DNA element (By similarity). May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (By similarity). Promotes myelin debris phagocytosis and remyelination by macrophages (By similarity). Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes (By similarity). Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (By similarity).
  subunit: Homodimer (By similarity). Heterodimer (via C-terminus) with RARA; required for ligand-dependent retinoic acid receptor transcriptional activity; association with RARA is enhanced by pulsatile shear stress (By similarity). Heterodimer with PPARA (via the leucine-like zipper in the LBD); the interaction is required for PPARA transcriptional activity (By similarity). Heterodimerizes with PPARG (By similarity). Heterodimerizes (via NR LBD) with RARB (By similarity). Heterodimerizes with NR1H4; the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators (By similarity). Interacts with NCOA3 and NCOA6 coactivators (By similarity). Interacts with FAM120B (By similarity). Interacts with coactivator PELP1, SENP6, SFPQ, DNTTIP2 and RNF8 (By similarity). Interacts with PRMT2 (By similarity). Interacts with ASXL1 (By similarity). Interacts with BHLHE40/DEC1, BHLHE41/DEC2, MED1, NCOR1 and NCOR2 (By similarity). Interacts in a ligand-dependent fashion with MED1 and NCOA1 (By similarity). Interacts with VDR (By similarity). Interacts with EP300; the interaction is decreased by 9-cis retinoic acid (By similarity). Heterodimer (via C-terminus) with NR4A1 (DNA- binding domain); the interaction is enhanced by 9-cis retinoic acid (By similarity). NR4A1 competes with EP300 for interaction with RXRA and thereby attenuates EP300 mediated acetylation of RXRA (By similarity). In the absence of hormonal ligand, interacts with TACC1 (By similarity). Interacts ith IGFBP3 (By similarity).

RXRA_HUMAN / P19793 Retinoic acid receptor RXR-alpha; Nuclear receptor subfamily 2 group B member 1; Retinoid X receptor alpha from Homo sapiens (Human) (see 37 papers)
NP_002948 retinoic acid receptor RXR-alpha isoform a from Homo sapiens
F1D8Q5 Retinoic acid receptor RXR from Homo sapiens
57% identity, 16% coverage

• function: Receptor for retinoic acid that acts as a transcription factor (PubMed:10874028, PubMed:11162439, PubMed:11915042, PubMed:37478846). Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:16107141, PubMed:17761950, PubMed:18800767, PubMed:19167885, PubMed:28167758, PubMed:37478846). The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:17761950, PubMed:28167758). The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:1310260). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:20215566). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (PubMed:20215566, PubMed:37478846, PubMed:9267036). Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (PubMed:10195690, PubMed:11915042, PubMed:28167758, PubMed:29021580). The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (PubMed:29021580). The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (PubMed:10195690). Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). Acts as an enhancer of RARA binding to RARE DNA element (PubMed:28167758). May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (PubMed:12145331, PubMed:15509776). Promotes myelin debris phagocytosis and remyelination by macrophages (PubMed:26463675). Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes (PubMed:25417649). Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (PubMed:30216632).
  subunit: Homodimer (PubMed:10669605, PubMed:17761950). Heterodimer (via C-terminus) with RARA; required for ligand-dependent retinoic acid receptor transcriptional activity; association with RARA is enhanced by pulsatile shear stress (PubMed:10698945, PubMed:15509776, PubMed:28167758). Heterodimer with PPARA (via the leucine-like zipper in the LBD); the interaction is required for PPARA transcriptional activity (PubMed:10195690, PubMed:11698662, PubMed:11915042). Heterodimerizes with PPARG (PubMed:10882139, PubMed:11698662). Heterodimerizes (via NR LBD) with RARB (PubMed:29021580). Heterodimerizes with NR1H4; the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators (PubMed:30275017). Interacts with NCOA3 and NCOA6 coactivators (PubMed:10567404, PubMed:9267036). Interacts with coactivator FAM120B (By similarity). Interacts with coactivator PELP1, SENP6, SFPQ, DNTTIP2 and RNF8 (PubMed:11259580, PubMed:14981089, PubMed:15047147, PubMed:16574651, PubMed:16912044). Interacts with PRMT2 (PubMed:12039952). Interacts with ASXL1 (By similarity). Interacts with BHLHE40/DEC1, BHLHE41/DEC2, NCOR1 and NCOR2 (PubMed:19786558). Interacts in a ligand-dependent fashion with MED1 and NCOA1 (PubMed:10882139, PubMed:11698662, PubMed:19786558). Interacts with VDR (PubMed:28698609). Interacts with EP300; the interaction is decreased by 9-cis retinoic acid (PubMed:17761950). Heterodimer (via C-terminus) with NR4A1 (via DNA- binding domain); DNA-binding of the heterodimer is enhanced by 9-cis retinoic acid (PubMed:15509776, PubMed:17761950). NR4A1 competes with EP300 for interaction with RXRA and thereby attenuates EP300 mediated acetylation of RXRA (PubMed:17761950). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863). Interacts ith IGFBP3 (PubMed:10874028).
  subunit: (Microbial infection) Interacts (via the DNA binding domain) with HCV core protein; the interaction enhances the transcriptional activities of the RXRA/RARA and the RXRA/PPARA heterodimers.
• Linc-ROR inhibits NK cell-killing activity by promoting RXRA ubiquitination and reducing MICB expression in gastric cancer patients.
  Niu, Journal of cellular biochemistry 2024 (PubMed)
  • GeneRIF: Linc-ROR inhibits NK cell-killing activity by promoting RXRA ubiquitination and reducing MICB expression in gastric cancer patients.
• ZNF148 inhibits HBV replication by downregulating RXRα transcription.
  Yao, Virology journal 2024
  • GeneRIF: ZNF148 inhibits HBV replication by downregulating RXRalpha transcription.
• Computational refinement identifies functional destructive single nucleotide polymorphisms associated with human retinoid X receptor gene.
  Sarkar, Journal of biomolecular structure & dynamics 2023 (PubMed)
  • GeneRIF: Computational refinement identifies functional destructive single nucleotide polymorphisms associated with human retinoid X receptor gene.
• lncRNA RMST suppresses the progression of colorectal cancer by competitively binding to miR-27a-3p/RXRα axis and inactivating Wnt signaling pathway.
  Chen, Acta biochimica et biophysica Sinica 2023
  • GeneRIF: lncRNA RMST suppresses the progression of colorectal cancer by competitively binding to miR-27a-3p/RXRalpha axis and inactivating Wnt signaling pathway.
• Stationary-to-migratory transition in glioblastoma stem-like cells driven by a fatty acid-binding protein 7-RXRα neurogenic pathway.
  Liu, Neuro-oncology 2023
  • GeneRIF: Stationary-to-migratory transition in glioblastoma stem-like cells driven by a fatty acid-binding protein 7-RXRalpha neurogenic pathway.
• SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 gene predict dosage requirements in a cross-sectional sample of hypothyroid patients.
  AlEjielat, BMC endocrine disorders 2023
  • GeneRIF: SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 gene predict dosage requirements in a cross-sectional sample of hypothyroid patients.
• The role of resveratrol, Sirtuin1 and RXRα as prognostic markers in ovarian cancer.
  Chen, Archives of gynecology and obstetrics 2022
  • GeneRIF: The role of resveratrol, Sirtuin1 and RXRalpha as prognostic markers in ovarian cancer.
• Cytoplasmic Colocalization of RXRα and PPARγ as an Independent Negative Prognosticator for Breast Cancer Patients.
  Shao, Cells 2022
  • GeneRIF: Cytoplasmic Colocalization of RXRalpha and PPARgamma as an Independent Negative Prognosticator for Breast Cancer Patients.
• More
• The transcriptome of metamorphosing flatfish
  Alves, BMC genomics 2016
  • “...a polypeptide 1 Cyp1a1 Q05A20 Mus musculus 3E-156 lcgut_c17435 Retinoid X nuclear receptor alpha Nr2b1 F1D8Q5 Homo sapiens 1E-76 Midgut development lcgut_c186 Retinal dehydrogenase 1 Aldh1a1 P24549 Mus musculus 2E-179 lcgut_c24118 Ornithine transcarbamylase, isoform CRA_a Otc Q543H3 Mus musculus 3E-72 lcgut_c2518 Arginase-2, mitochondrial Arg2 O08691 Mus...”
• Mechanistic Insights Into <i>Ganoderma Lucidum</i> for Diabetes Treatment via Network Pharmacology and Validation
  Guo, Diabetes, metabolic syndrome and obesity : targets and therapy 2025 (no snippet)
• Study of the multitarget mechanism of Astragalus (HUANGQI) in the treatment of Alzheimer's disease based on network pharmacology and molecular docking technology
  Lv, Pharmaceutical biology 2024
  • “...Uniprot ID Betweenness Centrality Closeness Centrality Degree 1 AR P10275 0.0254349 0.47854785 16 2 RXRA P19793 0.02442779 0.47540984 15 3 ESR1 P03372 0.017398 0.4723127 14 4 HSP90AA1 P07900 0.01842541 0.46925566 13 5 IL1B P01584 0.01819765 0.46623794 12 6 PPARG P37231 0.00780628 0.46031746 10 7 CALM1 P0DP23...”
• Retinoid X receptor heterodimers in hepatic function: structural insights and therapeutic potential
  Xu, Frontiers in pharmacology 2024
  • “...used for comparison: NP_001278849.01, NP_001257330.1, NP_001243499.1, NP_001277410.1, NP_001192143.1, and NP_001153203.1. 2.1 RXR RXR (UniProt ID: P19793), also known as nuclear receptor subfamily 2 group B member (NR2B1) is encoded by the human gene located at 9q34.2. The RXR protein consists of 462 amino acids with an...”
• Mechanism of Polygala-Acorus in Treating Autism Spectrum Disorder Based on Network Pharmacology and Molecular Docking
  Chen, Current computer-aided drug design 2024
  • “...F2 P00734 MIF P14174 NR1H2 P55055 ITGAL P20701 IGF1R P08069 PGR P06401 KIF11 P52732 RXRA P19793 BACE1 P56817 MAOB P27338 NR3C2 P08235 DDX6 P26196 MAPK14 Q16539 CALM1 P0DP23 FAP Q12884 MAPK8 P45983 FGFR1 P11362 AMY1A P0DUB6 MMP3 P08254 CDK6 Q00534 CFB P00751 SHBG P04278 WAS P42768...”
• Hierarchical multimodal self-attention-based graph neural network for DTI prediction.
  Bian, Briefings in bioinformatics 2024
  • “...P11473 Negative 9 Tyrosine-protein phosphatase non-receptor type 1 P18031 Negative 10 Retinoic acid receptor RXR-alpha P19793 Negative 11 Nuclear receptor coactivator 2 Q15596 Positive 12 Sex hormone-binding globulin P04278 Negative 13 Peroxisome proliferator-activated receptor gamma P37231 Negative 14 Mu-type opioid receptor P35372 Negative 15 Neuronal acetylcholine...”
• Insights from molecular network analysis to docking of sterubin with potential targets
  Viswanathan, Bioinformation 2023
  • “...45 AKT1 P31749 RAC-alpha serine/threonine-protein kinase 46 RIPK1 Q13546 Receptor-interacting serine/threonine-protein kinase 1 47 RXRA P19793 Retinoic acid receptor RXR-alpha 48 SHBG P04278 Sex hormone-binding globulin 49 STAT1 P42224 Signal transducer and activator of transcription 1-alpha/beta 50 SLCO2B1 O94956 Solute carrier organic anion transporter family member...”
• Toxic Relationships: Prediction of TBT's Affinity to the Ecdysteroid Receptor of Triops longicaudatus
  Ferreira, Toxics 2023
  • “...used for building the protein. Taxa Species Database Accession Number SWISS-MODEL Chordata Homo sapiens UniProt P19793 Q05343.1.A Arthropoda Acartia tonsa UniProt A0A4Y5X195 A0A4Y5X195.1.A Americamysis bahia NCBI DD410574 C3UZC9.1.A Crangon crangon UniProt C4N541 A0A171LJQ0.1.A Culex pipiens UniProt A0A8D8KFP5 A4F2F2.1.A Daphnia magna UniProt A4F2F2 A4F2F2.1.A Hyalella azteca UniProt...”
• Proteomic analysis reveals changes in the proteome of human THP-1 macrophages infected with Paracoccidioides brasiliensis
  de, Frontiers in cellular and infection microbiology 2023
  • “...820.58 * P14174 Macrophage migration inhibitory factor 4042.46 * Q96E17 Ras-related protein Rab-3C 1115.57 * P19793 Retinoic acid receptor RXR-alpha 654.98 * P28702 Retinoic acid receptor RXR-beta 1177.33 * P48443 Retinoic acid receptor RXR-gamma 630.23 * H0Y858 Toll-like receptor 9 (Fragment) 624.89 * A0A499FJK2 Transforming growth...”
• More

Q6LC96 Retinoic acid receptor RXR from Mus musculus
XP_006497868 retinoic acid receptor RXR-alpha isoform X1 from Mus musculus
57% identity, 17% coverage

• ITRAQ-based quantitative proteomic analysis of processed Euphorbia lathyris L. for reducing the intestinal toxicity.
  Zhang, Proteome science 2018
  • “...1 1.353 1.188 1.574 Q91YU8 Suppressor of SWI4 1homolog Ppan Ssf1 1 1.3522 1.167 1.1937 Q6LC96 RXR alpha 2 (RXR alpha 3) Rxra RXR alpha 1 1.329 0.984 1.2152 Q3UPV6 Voltage-gated potassium channel subunit beta-2 Kcnab2 1 1.328 1.568 1.183 P62301 40S ribosomal protein S13 Rps13...”
• Activation of RXRα exerts cardioprotection through transcriptional upregulation of Ndufs4 in heart failure.
  Shao, Science bulletin 2024 (PubMed)
  • GeneRIF: Activation of RXRalpha exerts cardioprotection through transcriptional upregulation of Ndufs4 in heart failure.
• Inhibition of RXRA-mediated PLA2G2A improves delirium in COPD mice by regulating endoplasmic reticulum stress pathway and inhibiting cell apoptosis.
  Zhang, Cellular and molecular biology (Noisy-le-Grand, France) 2024 (PubMed)
  • GeneRIF: Inhibition of RXRA-mediated PLA2G2A improves delirium in COPD mice by regulating endoplasmic reticulum stress pathway and inhibiting cell apoptosis.
• Transcriptional control of nucleus accumbens neuronal excitability by retinoid X receptor alpha tunes sensitivity to drug rewards.
  Godino, Neuron 2023
  • GeneRIF: Transcriptional control of nucleus accumbens neuronal excitability by retinoid X receptor alpha tunes sensitivity to drug rewards.
• Addiction neuroscience goes nuclear: A role for the transcription factor RXRα.
  Pierce, Neuron 2023 (PubMed)
  • GeneRIF: Addiction neuroscience goes nuclear: A role for the transcription factor RXRalpha.
• The Transcription Factor RXRα in CD11c+ APCs Regulates Intestinal Immune Homeostasis and Inflammation.
  Manoharan, Journal of immunology (Baltimore, Md. : 1950) 2023
  • GeneRIF: The Transcription Factor RXRalpha in CD11c+ APCs Regulates Intestinal Immune Homeostasis and Inflammation.
• RXRA DT448/9PP generates a dominant active variant capable of inducing maturation in acute myeloid leukemia cells.
  Di, Haematologica 2022
  • GeneRIF: RXRA DT448/9PP generates a dominant active variant capable of inducing maturation in acute myeloid leukemia cells.
• Phosphorylation of RXRα mediates the effect of JNK to suppress hepatic FGF21 expression and promote metabolic syndrome.
  Vernia, Proceedings of the National Academy of Sciences of the United States of America 2022
  • GeneRIF: Phosphorylation of RXRalpha mediates the effect of JNK to suppress hepatic FGF21 expression and promote metabolic syndrome.
• Integrated analysis of mRNA-seq and miRNA-seq reveals the potential roles of Egr1, Rxra and Max in kidney stone disease.
  Huang, Urolithiasis 2022 (PubMed)
  • GeneRIF: Integrated analysis of mRNA-seq and miRNA-seq reveals the potential roles of Egr1, Rxra and Max in kidney stone disease.
• More

XP_020927262 retinoic acid receptor RXR-alpha isoform X1 from Sus scrofa
57% identity, 17% coverage

• Differential regulation of TauT by calcitriol and retinoic acid via VDR/RXR in LLC-PK1 and MCF-7 cells.
  Chesney, Advances in experimental medicine and biology 2013 (PubMed)
  • GeneRIF: Expression of TauT is differentially regulated by Vitamin D(3) and retinoic acid via formation of VDR and RXR complexes in the nuclei in a cell type-dependent manner.

Q8VIJ4 Nuclear receptor subfamily 2 group C member 1 from Rattus norvegicus
65% identity, 12% coverage

• Mechanobiological responses of astrocytes in optic nerve head due to biaxial stretch.
  Li, BMC ophthalmology 2022
  • “...Q3MHC1 cytoskeleton 10%24h 17%24h 0.43 0.41 Nuclear receptor subfamily 2 group C member 1 (NR2C1) Q8VIJ4 nucleus 10%24h 17%24h 0.58 0.39 * The average value of Fold Change obtained from three technical repetitions is shown GO and KEGG enrichment analysis of differential proteins Through GO enrichment...”

NR2C1_MOUSE / Q505F1 Nuclear receptor subfamily 2 group C member 1; Orphan nuclear receptor TR2; Testicular receptor 2; mTR2 from Mus musculus (Mouse) (see 19 papers)
NP_035759 nuclear receptor subfamily 2 group C member 1 from Mus musculus
64% identity, 12% coverage

• function: Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes including ESR1 and RARB. Together with NR2C2, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences (By similarity). Also activator of OCT4 gene expression. Plays a fundamental role in early embryogenesis and regulates embryonic stem cell proliferation and differentiation. Mediator of retinoic acid- regulated preadipocyte proliferation.
  subunit: Homodimer. Heterodimer; with NR2C2 which is required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with ESR1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth (By similarity). Interacts with NRIP1 (via its LXXLL motifs); the interaction provides corepressor activity. Interacts with HDAC3 (via the DNA-binding domain); the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation. Interacts with HDAC4 (via the DNA-binding domain). Interacts with PIAS1; the interaction is required for sumoylation of NR2C1. Interacts with UBE2I; the interaction is required for sumoylation of NR2C1. Interacts with KAT2B; the interaction acts as a corepressor of gene expression.
  disruption phenotype: No visible phenotype. Mice exhibit normal spermatogenesis and testis development, as well as normal central nervous system development. NR2C1 and NR2C2 double null mutants result in early embryonic lethality and increased apoptosis. Embryos die around 7.5 dpc.
• The nuclear hormone receptor gene Nr2c1 (Tr2) is a critical regulator of early retina cell patterning.
  Olivares, Developmental biology 2017 (PubMed)
  • GeneRIF: This study supports a role for Nr2c1 in defining the biphasic period of retinal development and specifically influencing the early phase of retinal cell fate.
• Testicular receptor 2, Nr2c1, is associated with stem cells in the developing olfactory epithelium and other cranial sensory and skeletal structures.
  Baker, Gene expression patterns : GEP 2016
  • GeneRIF: Nr2c1 may be a candidate for mediating parallel adaptive changes in cranial neural sensory specializations such as the olfactory epithelium, retina and mystacial vibrissae and in non-neural craniofacial features including teeth
• Nuclear receptors TR2 and TR4 recruit multiple epigenetic transcriptional corepressors that associate specifically with the embryonic β-type globin promoters in differentiated adult erythroid cells.
  Cui, Molecular and cellular biology 2011
  • GeneRIF: in adult erythroid cells, TR2/TR4 bind to the embryonic beta-type globin promoters but not to the adult beta-globin promoter.
• Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes.
  Campbell, Proceedings of the National Academy of Sciences of the United States of America 2011
  • GeneRIF: TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes
• Roles of testicular orphan nuclear receptors 2 and 4 in early embryonic development and embryonic stem cells.
  Shyr, Endocrinology 2009 (PubMed)
  • GeneRIF: Possible roles for TR2 and TR4 in early embryonic development by regulating key genes involved in stem cell self-renewal, commitment, and differentiation.
• HDAC3 as a molecular chaperone for shuttling phosphorylated TR2 to PML: a novel deacetylase activity-independent function of HDAC3.
  Gupta, PloS one 2009
  • GeneRIF: This is the first report identifying a deacetylase-independent function for HDAC3, which serves as a specific carrier molecule that targets a specifically phosphorylated protein to promyelocytic leukemia (PML) nuclear bodies.
• Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression.
  Gupta, Proceedings of the National Academy of Sciences of the United States of America 2008
  • GeneRIF: Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression
• SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4 expression in stem cells.
  Park, Nature structural & molecular biology 2007 (PubMed)
  • GeneRIF: These results suggest a SUMOylation-dependent partitioning and differential coregulator recruitment contribute to the maintenance of a homeostatic supply of activating, Tr2, thus fine-tuning Oct4 expression and regulating stem-cell proliferation.
• More

P31396 Probable nuclear hormone receptor HR3 from Drosophila melanogaster
63% identity, 15% coverage

• RNA sequencing indicates widespread conservation of circadian clocks in marine zooplankton
  Raghavan, NAR genomics and bioinformatics 2023
  • “...Mm: NFIL3 (O08750) Mammalian REV-ERBa (Mm Q3UV55) Dm: EIP75B (P13055) RORa (Mm P51448) Dm: HR3 (P31396) Indicated in the left column are the baits, and in the right their counterparts. Alongside the protein name of the bait and the source organism, the sequences UniProt identifier is...”
• Expression and ecdysteroid responsiveness of the nuclear receptors HR3 and E75 in the crustacean Daphnia magna
  Hannas, Molecular and cellular endocrinology 2010
  • “...A 148 bp fragment with identity to HR3 of other species (GenBank accession numbers: AAF36970, P31396, NP_001037012) was obtained by CODEHOP-PCR (as above). The hybrid consensus-degenerate primer sequences were as follows: 5-TGATCGAGTTAATCGAAATCGATGYCARTAYTG -3 and 5-GAGCAGCATCAGATTGAGCTCKCATYTGNGC -3. One round of standard 3-step PCR was performed, using an...”

NR2C1_HUMAN / P13056 Nuclear receptor subfamily 2 group C member 1; Orphan nuclear receptor TR2; Testicular receptor 2 from Homo sapiens (Human) (see 2 papers)
NP_003288 nuclear receptor subfamily 2 group C member 1 isoform a from Homo sapiens
65% identity, 12% coverage

• function: Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Together with NR2C2, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription. Also activator of OCT4 gene expression. May be involved in stem cell proliferation and differentiation. Mediator of retinoic acid-regulated preadipocyte proliferation.
  subunit: Homodimer (By similarity). Heterodimer; binds DNA as a heterodimer with NR2C2 required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats (By similarity). Interacts with NRIP1 (via its LXXLL motifs); the interaction provides corepressor activity. Interacts with HDAC3 (via the DNA-binding domain). Interacts with HDAC4 (via the DNA-binding domain). Interacts with PIAS1; the interaction is required for sumoylation of NR2C1. Interacts with UBE2I; the interaction is required for sumoylation of NR2C1. Interacts with KAT2B; the interaction acts as a corepressor of gene expression (By similarity). Interacts with ESR1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth.
• THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2021
  • “...Nomenclature Testicular receptor 2 Testicular receptor 4 Systematic nomenclature NR2C1 NR2C2 HGNC, UniProt NR2C1 , P13056 NR2C2 , P49116 Endogenous agonists retinol [ 169 ], tretinoin [ 169 ] Comments Forms a heterodimer with TR4; gene disruption appears without effect on testicular development or function [...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2017
  • “...Nomenclature Testicular receptor 2 Testicular receptor 4 Systematic nomenclature NR2C1 NR2C2 HGNC, UniProt NR2C1 , P13056 NR2C2 , P49116 Endogenous agonists retinol [ 169 ], tretinoin [ 169 ] Comments Forms a heterodimer with TR4; gene disruption appears without effect on testicular development or function [...”
• The Concise Guide to PHARMACOLOGY 2015/16: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2015
  • “...Nomenclature Testicular receptor 2 Testicular receptor 4 Systematic nomenclature NR2C1 NR2C2 HGNC, UniProt NR2C1 , P13056 NR2C2 , P49116 Endogenous agonists retinol (Selective) [ 173 ], tretinoin (Selective) [ 173 ] Comments Forms a heterodimer with TR4; gene disruption appears without effect on testicular development or...”
• The Concise Guide to PHARMACOLOGY 2013/14: nuclear hormone receptors
  Alexander, British journal of pharmacology 2013
  • “...retinoids. Nomenclature Testicular receptor 2 Testicular receptor 4 Systematic nomenclature NR2C1 NR2C2 HGNC, UniProt NR2C1, P13056 NR2C2, P49116 Endogenous agonists (pKi) all-trans-retinoic acid (Selective) [ 96 ], retinol (Selective) [ 96 ] Comment Forms a heterodimer with TR4; gene disruption appears without effect on testicular development...”
• A manually curated network of the PML nuclear body interactome reveals an important role for PML-NBs in SUMOylation dynamics
  Van, International journal of biological sciences 2010
  • “...K451 SUMOylation of TIP60 augments its acetyltransferase activity in vitro and in vivo 149 + P13056 TR2 NDSM SUMOylated TR2 recruits corepressor RIP140 to act as a repressor for its target Oct4 150 - O95551 TTRAP Unknown Q9UBW7 ZNF198 K963 SUMOylation of ZNF198 is important for...”
• NamiRNA-enhancer network of miR-492 activates the NR2C1-TGF-β/Smad3 pathway to promote epithelial-mesenchymal transition of pancreatic cancer.
  Liu, Carcinogenesis 2023 (PubMed)
  • GeneRIF: NamiRNA-enhancer network of miR-492 activates the NR2C1-TGF-beta/Smad3 pathway to promote epithelial-mesenchymal transition of pancreatic cancer.
• Transcriptional regulation of the human TR2 orphan receptor gene by nuclear factor 1-A.
  Lin, Biochemical and biophysical research communications 2006 (PubMed)
  • GeneRIF: The NF1-A transcription factor plays an important role in the transcriptional activation of the TR2 gene expression via a promoter activating cis-element.
• Differential and bi-directional regulation between TR2/TR4 orphan nuclear receptors and a specific ligand mediated-peroxisome proliferator-activated receptor alpha in human HaCaT keratinocytes.
  Inui, Journal of dermatological science 2003 (PubMed)
  • GeneRIF: TR2 and TR4 can have distinct functions. Existence of differential and bi-directional regulation between PPAR alpha and TR2/TR4. Possible roles in PPAR alpha signaling pathway in human keratinocytes.
• TR2 orphan receptor functions as negative modulator for androgen receptor in prostate cancer cells PC-3.
  Mu, The Prostate 2003 (PubMed)
  • GeneRIF: TR2 may function as a negative modulator to suppress androgen receptor function in prostate cancer. Further studies on how to control TR2 function may result in the ability to modulate AR function in prostate cancer.
• An embryonic/fetal beta-type globin gene repressor contains a nuclear receptor TR2/TR4 heterodimer.
  Tanabe, The EMBO journal 2002
  • GeneRIF: DRED is a 540 kDa complex containing the nuclear orphan receptors TR2 and TR4, which form a heterodimer that binds to the epsilon and gamma globin promoter DR1 sites. TR2 & 4 mRNAs are expressed at all stages of murine and human erythropoiesis.
• Suppression of estrogen receptor-mediated transcription and cell growth by interaction with TR2 orphan receptor.
  Hu, The Journal of biological chemistry 2002 (PubMed)
  • GeneRIF: TR2 that may exert an important repressor in regulating ER activity in mammary glands.
• Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
  Rose, Molecular medicine (Cambridge, Mass.)
  • GeneRIF: Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)

RXRAA_DANRE / A2T929 Retinoic acid receptor RXR-alpha-A; Nuclear receptor subfamily 2 group B member 1-A; RXRalpha-B; Retinoid X receptor alpha-A from Danio rerio (Zebrafish) (Brachydanio rerio) (see 2 papers)
57% identity, 17% coverage

• function: Receptor for retinoic acid that acts as a transcription factor. Forms homo- or heterodimers with retinoic acid receptors (rars) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription. The high affinity ligand for rxrs is 9-cis retinoic acid. In the absence of ligand, the rar/rxr heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation.
  subunit: Homodimer. Heterodimer; with a rar molecule. Binds DNA preferentially as a rar/rxr heterodimer.

XP_008195824 probable nuclear hormone receptor HR3 isoform X7 from Tribolium castaneum
64% identity, 15% coverage

• Role of nuclear receptors NlHR3 and NlFTZ-F1 in regulating molting and reproduction in Nilaparvata lugens (stål)
  Li, Frontiers in physiology 2023
  • “...Nasonia vitripennis , XP_008202385), TcHR3X1 ( Tribolium castaneum , XP_974561), TcHR3X2 ( Tribolium castaneum , XP_008195824), and TcHR3X3 ( Tribolium castaneum , XP_008195825). Amino acids with 100, > 80, and > 60% conservations are shaded in black, dark gray, and light gray, respectively. Gaps have been...”

HNF4_DROME / P49866 Transcription factor HNF-4 homolog; dHNF4; Nuclear receptor subfamily 2 group A member 4 from Drosophila melanogaster (Fruit fly) (see 2 papers)
NP_476887 hepatocyte nuclear factor 4, isoform A from Drosophila melanogaster
NP_723414 hepatocyte nuclear factor 4, isoform E from Drosophila melanogaster
57% identity, 11% coverage

• function: Transcriptionally controlled transcription factor. Important for the differentiation of various specialized cell types that arise from both endoderm and mesoderm. May have a role in early gut formation. Plays an essential role in lipid catabolism, regulating lipid mobilization and beta-oxidation in response to nutrient deprivation.
  subunit: Homodimer.
  disruption phenotype: Under normal culture conditions, the flies progress through development until they die during or shortly after adult eclosion. Under low density culture conditions, many flies survive and develop into morphologically normal adults. The mutant flies are, however, very sensitive to starvation, displaying inability to efficiently mobilize stored lipid in the midgut and fat body, increased levels of long-chain fatty acids and triglycerides, and premature death.
• The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans
  Liang, PloS one 2010
  • “...Amino acid alignment of HNF4 genes. Shown are human HsHF4 (NP_849180), mouse MmHF4(NP_032287), Drosophila DeHF4 (NP_476887), and C. elegans NHR-64(AAC24283). DBD: DNA binding domain; LBD: ligand binding domain. E: Glutamic acid residue; L: Leucine residue. Sequences of amino acid covered with gray color are encoded by...”
• Drosophila HNF4 acts in distinct tissues to direct a switch between lipid storage and export in the gut.
  Vonolfen, Cell reports 2024 (PubMed)
  • GeneRIF: Drosophila HNF4 acts in distinct tissues to direct a switch between lipid storage and export in the gut.
• Integrating lipid metabolism, pheromone production and perception by Fruitless and Hepatocyte Nuclear Factor 4.
  Sun, Science advances 2023
  • GeneRIF: Integrating lipid metabolism, pheromone production and perception by Fruitless and Hepatocyte Nuclear Factor 4.
• dHNF4 regulates lipid homeostasis and oogenesis in Drosophila melanogaster.
  Almeida-Oliveira, Insect biochemistry and molecular biology 2021 (PubMed)
  • GeneRIF: dHNF4 regulates lipid homeostasis and oogenesis in Drosophila melanogaster.
• Drosophila HNF4 Directs a Switch in Lipid Metabolism that Supports the Transition to Adulthood.
  Storelli, Developmental cell 2019
  • GeneRIF: establish dHNF4 as a regulator of the adult metabolic state
• Molecular Basis for Autosomal-Dominant Renal Fanconi Syndrome Caused by HNF4A.
  Marchesin, Cell reports 2019
  • GeneRIF: Molecular Basis for Autosomal-Dominant Renal Fanconi Syndrome Caused by HNF4A.
• Sir2 Acts through Hepatocyte Nuclear Factor 4 to maintain insulin Signaling and Metabolic Homeostasis in Drosophila.
  Palu, PLoS genetics 2016
  • GeneRIF: Drosophila HNF4 mutants display diabetic phenotypes similar to those of sir2 mutants, and protein levels for dHNF4 are reduced in sir2 mutant animals. Sir2 exerts these effects by deacetylating and stabilizing dHNF4 through protein interactions.
• The Drosophila HNF4 nuclear receptor promotes glucose-stimulated insulin secretion and mitochondrial function in adults.
  Barry, eLife 2016
  • GeneRIF: Here the authors report that loss of Drosophila HNF4 recapitulates hallmark symptoms of Maturity Onset Diabetes of the Young 1 (MODY1), including adult-onset hyperglycemia, glucose intolerance and impaired glucose-stimulated insulin secretion (GSIS).
• Drosophila HNF4 regulates lipid mobilization and beta-oxidation.
  Palanker, Cell metabolism 2009
  • GeneRIF: Results support a feed-forward model for dHNF4, in which fatty acids released from triglycerides activate the receptor, inducing enzymes that drive fatty acid oxidation for energy production.

NP_001186756 RAR-related orphan receptor C a from Oncorhynchus mykiss
63% identity, 16% coverage

• Cloning and expression analysis of two ROR-γ homologues (ROR-γa1 and ROR-γa2) in rainbow trout Oncorhynchus mykiss.
  Monte, Fish & shellfish immunology 2012 (PubMed)
  • GeneRIF: a potential role of trout ROR-gamma, a putative T(H)17 transcription factor, in protection against extracellular bacteria

RXRA_XENLA / P51128 Retinoic acid receptor RXR-alpha; Nuclear receptor subfamily 2 group B member 1; Retinoid X receptor alpha from Xenopus laevis (African clawed frog) (see 2 papers)
57% identity, 15% coverage

• function: Receptor for retinoic acid that acts as a transcription factor. Forms homo- or heterodimers with retinoic acid receptors (rars) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription. The high affinity ligand for rxrs is 9-cis retinoic acid. In the absence of ligand, the rar/rxr heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation.
  subunit: Homodimer. Heterodimer; with a rar molecule. Binds DNA preferentially as a rar/rxr heterodimer (By similarity). Interacts with coactivator ncoa3 and with senp6 (PubMed:16912044, PubMed:9658407).
• Molecular characterization of RXR (Retinoid X Receptor) gene isoforms from the bivalve species Chlamys farreri
  Lv, PloS one 2013
  • “...RXR (GenBank ID: AAU12572); T. molitor USP (GenBank ID: CAB75361); X. laevis RXR-alpha (GenBank ID: P51128); X. laevis RXR-beta (GenBank ID:NP_001080936); X. laevis RXR-gamma (GenBank ID:NP_001088948). CfRXRs mRNA expression profiles To examine the expression levels of CfRXR s in scallop gonads during different developmental stages, total...”

XP_010801017 retinoic acid receptor RXR-gamma isoform X1 from Bos taurus
58% identity, 18% coverage

• [Genetic variation in RXRG gene and its relationship with twinning trait in cattle].
  Huang, Yi chuan = Hereditas 2008 (PubMed)
  • GeneRIF: Retinoic X receptor-gamma (RXRG) gene was studied as a candidate gene for the twinning trait of bovine.

NR2F6_RAT / O09017 Nuclear receptor subfamily 2 group F member 6; COUPg; Ovalbumin upstream promoter gamma nuclear receptor; V-erbA-related protein 2; EAR-2 from Rattus norvegicus (Rat) (see paper)
61% identity, 18% coverage

• function: Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin- choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine- dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4(+) T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC) (By similarity).
  subunit: Binds DNA as dimer; homodimer and heterodimer with NR2F2 and probably NR2F1. Interacts with THRB (By similarity).

NP_849180 hepatocyte nuclear factor 4-alpha isoform 1 from Homo sapiens
54% identity, 16% coverage

• The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: implications for developing new model organisms
  Kaur, PloS one 2015
  • “...1K HR1 AAC48174 2A HR49 CAD57702 HNF4 CCD80248 HNF4 AAF52702 BgHNF4 2702 LgHNF4 73247 HNF4 NP_849180 HNF4 NP_004124 2B RXR1 CCD59553 USP AAF45707 BgRXR 3695 LgRXR 206562 RXR AAI10999 RXR2 AAD33428 RXR AAC18599 RXR AAA80681 2C/D HR41 NP_500073 TR AAV80236 HR78 Q24142 BgTR 2718 LgTR *...”

XP_017209577 nuclear receptor ROR-alpha A isoform X1 from Danio rerio
66% identity, 14% coverage

• Expression of zebrafish ROR alpha gene in cerebellar-like structures.
  Katsuyama, Developmental dynamics : an official publication of the American Association of Anatomists 2007 (PubMed)
  • GeneRIF: study reports cloning and expression pattern of zebrafish ROR alpha orthologues rora1 and rora2; both rora1 and rora2 are spatially expressed in the retina and tectum; expression of rora2 was further observed in the cerebellum

E75BC_DROME / P17671 Ecdysone-induced protein 75B, isoforms C/D; E75-A; Nuclear receptor subfamily 1 group D member 3, isoforms C/D from Drosophila melanogaster (Fruit fly) (see paper)
62% identity, 6% coverage

• function: Implicated in the regulation of ecdysone-triggered gene hierarchies. Probably plays a key role in mediating the regulation of the larval molt by 20-OH-ecdysone.

NR2F6_MOUSE / P43136 Nuclear receptor subfamily 2 group F member 6; COUP transcription factor 3; COUP-TF3; V-erbA-related protein 2; EAR-2 from Mus musculus (Mouse) (see 3 papers)
62% identity, 18% coverage

• function: Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin- choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine- dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4(+) T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC).
  subunit: Binds DNA as dimer; homodimer and heterodimer with NR2F2 and probably NR2F1. Interacts with THRB (By similarity).
  disruption phenotype: Reduction of neurons in the locus coerulus of the developing cortex. Defects in circadian behavior. Hyperreactive lymphocytes, late-onset immunopathology and hypersusceptibility to Th17-dependent experimental autoimmune encephalomyelitis.
• A proteomic analysis reveals that Snail regulates the expression of the nuclear orphan receptor Nuclear Receptor Subfamily 2 Group F Member 6 (Nr2f6) and interleukin 17 (IL-17) to inhibit adipocyte differentiation.
  Peláez-García, Molecular & cellular proteomics : MCP 2015

NR2F6_HUMAN / P10588 Nuclear receptor subfamily 2 group F member 6; V-erbA-related protein 2; EAR-2 from Homo sapiens (Human) (see 4 papers)
NP_005225 nuclear receptor subfamily 2 group F member 6 from Homo sapiens
62% identity, 18% coverage

• function: Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin- choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine- dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4(+) T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC).
  subunit: Binds DNA as dimer; homodimer and heterodimer with NR2F2 and probably NR2F1 (By similarity). Interacts with THRB.
• UPK3A+ umbrella cell damage mediated by TLR3-NR2F6 triggers programmed destruction of urothelium in Hunner-type interstitial cystitis/painful bladder syndrome.
  Peng, The Journal of pathology 2024 (PubMed)
  • GeneRIF: UPK3A[+] umbrella cell damage mediated by TLR3-NR2F6 triggers programmed destruction of urothelium in Hunner-type interstitial cystitis/painful bladder syndrome.
• Concerted regulation of skeletal muscle metabolism and contractile properties by the orphan nuclear receptor Nr2f6.
  Guimarães, Journal of cachexia, sarcopenia and muscle 2024
  • GeneRIF: Concerted regulation of skeletal muscle metabolism and contractile properties by the orphan nuclear receptor Nr2f6.
• Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients.
  Proppe, Journal of cancer research and clinical oncology 2023
  • GeneRIF: Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients.
• NR2F6, a new immune checkpoint that acts as a potential biomarker of immunosuppression and contributes to poor clinical outcome in human glioma.
  Miftah, Frontiers in immunology 2023
  • GeneRIF: NR2F6, a new immune checkpoint that acts as a potential biomarker of immunosuppression and contributes to poor clinical outcome in human glioma.
• Incomplete thermal ablation-induced up-regulation of transcription factor nuclear receptor subfamily 2, group F, member 6 (NR2F6) contributes to the rapid progression of residual liver tumor in hepatoblastoma.
  Pang, Bioengineered 2021
  • GeneRIF: Incomplete thermal ablation-induced up-regulation of transcription factor nuclear receptor subfamily 2, group F, member 6 (NR2F6) contributes to the rapid progression of residual liver tumor in hepatoblastoma.
• [The role of nuclear receptor transcription factor NR2F6 in tumor].
  Huang, Sheng wu gong cheng xue bao = Chinese journal of biotechnology 2021 (PubMed)
  • GeneRIF: [The role of nuclear receptor transcription factor NR2F6 in tumor].
• Regulation of docetaxel chemosensitivity by NR2F6 in breast cancer.
  Zhang, Endocrine-related cancer 2020 (PubMed)
  • GeneRIF: Regulation of docetaxel chemosensitivity by NR2F6 in breast cancer.
• NR2F6 as a Prognostic Biomarker in HNSCC.
  Klapper, International journal of molecular sciences 2020
  • GeneRIF: NR2F6 as a Prognostic Biomarker in HNSCC.
• More
• THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2021
  • “...Systematic nomenclature NR2F1 NR2F2 NR2F6 HGNC, UniProt NR2F1 , P10589 NR2F2 , P24468 NR2F6 , P10588 Comments Gene disruption is perinatally lethal [ 118 ]. Gene disruption is embryonically lethal [ 115 ]. Gene disruption impairs CNS development [ 151 ]. 3B. Estrogenrelated receptors Overview Estrogenrelated...”
• DUSP7 inhibits cervical cancer progression by inactivating the RAS pathway.
  Bai, Journal of cellular and molecular medicine 2021
  • “...Q6UXS93 CASP12 2.21 1.60 2.16 Q5TD07 NQO2 1.55 1.73 1.99 Q9UK585 CCNL1 1.76 1.99 1.52 P10588 NR2F6 1.87 1.71 2.57 E9PNW4 CD59 1.50 1.83 1.58 V9GY00 PBLD 2.48 1.84 1.42 O43866 CD5L 1.40 2.40 1.62 A0A087WVF8 PDE4DIP 2.93 1.51 1.62 H0YMY6 CERS4 1.52 1.62 1.58 P16234...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2017
  • “...Systematic nomenclature NR2F1 NR2F2 NR2F6 HGNC, UniProt NR2F1 , P10589 NR2F2 , P24468 NR2F6 , P10588 Comments Gene disruption is perinatally lethal [ 120 ]. Gene disruption is embryonically lethal [ 117 ]. Gene disruption impairs CNS development [ 151 ]. Further reading on 2F. COUPTFlike...”
• The Concise Guide to PHARMACOLOGY 2015/16: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2015
  • “...Systematic nomenclature NR2F1 NR2F2 NR2F6 HGNC, UniProt NR2F1 , P10589 NR2F2 , P24468 NR2F6 , P10588 Comments Gene disruption is perinatally lethal [ 121 ]. Gene disruption is embryonically lethal [ 118 ]. Gene disruption impairs CNS development [ 155 ]. Further Reading Benoit G et...”
• The Concise Guide to PHARMACOLOGY 2013/14: nuclear hormone receptors
  Alexander, British journal of pharmacology 2013
  • “...COUP-TF2 V-erbA-related gene Systematic nomenclature NR2F1 NR2F2 NR2F6 HGNC, UniProt NR2F1, P10589 NR2F2, P24468 NR2F6, P10588 Comment Gene disruption is perinatally lethal 102 Gene disruption is embryonically lethal 101 Gene disruption impairs CNS development 103 Further reading Benoit G Cooney A Giguere V Ingraham H Lazar...”
• Complementary quantitative proteomics reveals that transcription factor AP-4 mediates E-box-dependent complex formation for transcriptional repression of HDM2
  Ku, Molecular & cellular proteomics : MCP 2009
  • “...522 9 2.26 0.34 2.00 0.33 P78347 Q9NZI7 P10589 P24468 P08651 P10588 GTF2I UBP1 NR2F1 NR2F2 NFIC NR2F6 112346 60453 46126 45542 55640 42952 141 903 316 228 85 78...”

D2XNK4 Retinoid X receptor-like protein (Fragment) from Saccoglossus kowalevskii
57% identity, 14% coverage

• Exploring the Potential Hormonal Effects of Tire Polymers (TPs) on Different Species Based on a Theoretical Computational Approach.
  Wang, Polymers 2023
  • “...UniProt Freshwater fish BAH11081.1 NCBI Q766D2 NCBI P50241 UniProt Marine environment Marine nematodes A0A0U2IDR0 UniProt D2XNK4 NCBI B5THM8 UniProt Mussels A0A8B6HK24 UniProt A0A4Y5MV01 UniProt A0A8B6H7D5 UniProt Crabs A0A6B9F3J7 UniProt MPC23433.1 NCBI A0A097C257 UniProt Marine fish 2ACE PDB Q9W6I9 NCBI P16058 UniProt Soil environment Soil nematodes Q65XS8...”

E75BB_DROME / P13055 Ecdysone-induced protein 75B, isoform B; E75-C; Nuclear receptor subfamily 1 group D member 3, isoform B from Drosophila melanogaster (Fruit fly) (see paper)
NP_001246822 Ecdysone-induced protein 75B, isoform F from Drosophila melanogaster
NP_730321 Ecdysone-induced protein 75B, isoform B from Drosophila melanogaster
62% identity, 5% coverage

• function: Implicated in the regulation of ecdysone-triggered gene hierarchies. Probably plays a key role in mediating the regulation of the larval molt by 20-OH-ecdysone.
• A Single Nucleotide Variant in the PPARγ-homolog Eip75B Affects Fecundity in Drosophila.
  Hoedjes, Molecular biology and evolution 2023
  • GeneRIF: A Single Nucleotide Variant in the PPARgamma-homolog Eip75B Affects Fecundity in Drosophila.
• Nitric Oxide as a Switching Mechanism between Axon Degeneration and Regrowth during Developmental Remodeling.
  Rabinovich, Cell 2016
  • GeneRIF: These results suggest that E75C, like UNF, is required for developmental regrowth, but not initial outgrowth of mushroom body gamma axons.
• Transcriptional regulation via nuclear receptor crosstalk required for the Drosophila circadian clock.
  Jaumouillé, Current biology : CB 2015
  • GeneRIF: E75 and UNF bind to PER regulatory sequences and act together to enhance the CLK/CYC-mediated transcription of the PER gene.
• An ecdysone-responsive nuclear receptor regulates circadian rhythms in Drosophila.
  Kumar, Nature communications 2014
  • GeneRIF: E75 and ecdysone receptor are expressed in central clock cells, and manipulations of their expression produce drastic effects on circadian rhythms in Drosophila.
• Covalent attachment of heme to the protein moiety in an insect E75 nitric oxide sensor.
  Aicart-Ramos, Biochemistry 2012
  • GeneRIF: Covalent attachment of heme to the protein moiety in an insect E75 nitric oxide sensor.
• Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75.
  Cáceres, Genes & development 2011
  • GeneRIF: nitric oxide is produced in the Drosophila prothoracic gland, where it acts via the nuclear receptor ecdysone-induced protein 75 (E75), reversing its ability to interfere with its heterodimer partner, Drosophila hormone receptor 3 (DHR3).
• The Drosophila FTZ-F1 nuclear receptor mediates juvenile hormone activation of E75A gene expression through an intracellular pathway.
  Dubrovsky, The Journal of biological chemistry 2011
  • GeneRIF: FTZ-F1 functions as a competence factor by loading juvenile hormone (JH) signaling components to the promoter, thus facilitating the direct regulation of E75A gene expression by JH.
• Ecdysone- and NO-mediated gene regulation by competing EcR/Usp and E75A nuclear receptors during Drosophila development.
  Johnston, Molecular cell 2011
  • GeneRIF: Ecdysone and NO mediate gene regulation by competing EcR/Usp and E75A nuclear receptors during Drosophila development
• More
• Identification and temporal expression of putative circadian clock transcripts in the amphipod crustacean Talitrus saltator
  O'Grady, PeerJ 2016
  • “...EBONY AAF55870 comp99283_c0_seq2 4,380 Tal-EBONY Full 974 RORA NP_788301 comp99654_c0_seq3 2,217 Tal-RORA Partial 599 REVERB NP_730321 comp101252_c0_seq2 5,385 Tal-REVERB Full 1,110 SIRT1 NP_477351 comp101818_c1_seq1 4,033 Tal-SIRT1 Partial 955 SIRT2 NP_650880 comp97450_c0_seq4 2,275 Tal-SIRT2 Partial 376 SIRT4 NP_572241 comp92313_c0_seq2 2,977 Tal-SIRT4 Partial 354 SIRT6 NP_649990 comp69157_c0_seq1 1,209...”
  • “...Figure S20 Putative Talitrus saltator REVERB protein Alignment of Drosophila melanogaster E75 (Drome-E75; Accession No. NP_730321 ) with the T. saltator (Tal-REVERB) deduced from the Trinity de novo transcriptome assembly, together with the top two tblastn species homologue sequences Blattella germanica E75 (Blage-E75; Accession No. AM710419...”
• RNA sequencing indicates widespread conservation of circadian clocks in marine zooplankton
  Raghavan, NAR genomics and bioinformatics 2023
  • “...(Q8BW74), TEF (Q9JLC6) VRI (Dm Q9VMS4) Mm: NFIL3 (O08750) Mammalian REV-ERBa (Mm Q3UV55) Dm: EIP75B (P13055) RORa (Mm P51448) Dm: HR3 (P31396) Indicated in the left column are the baits, and in the right their counterparts. Alongside the protein name of the bait and the source...”
• Trinucleotide repeats and long homopeptides in genes and proteins associated with nervous system disease and development
  Karlin, Proceedings of the National Academy of Sciences of the United States of America 1996
  • “...P5, Q25, Q5 Q5, Q6, Q6, Alo Dorsal (P15330) AEFI (P39413) E75-C (P13055) 678 Qs, Qs, Q6, QO4, A., Q7 308 N5, Q13, Q6 1443 Q5, Q7, P1s, Q6, Q6, S7, S6, Q8, P8,...”

XP_017909032 nuclear receptor ROR-alpha isoform X1 from Capra hircus
66% identity, 14% coverage

• Expression of the RORα gene in Inner Mongolian cashmere goat hair follicles.
  Zhao, Genetics and molecular research : GMR 2015 (PubMed)
  • GeneRIF: RORalphawas expressed in secondary hair follicles of the hair shaft, inner root sheath, outer root sheath, medulla, and other parts that are target organs of the RORalphareceptor gene.

RORA_HUMAN / P35398 Nuclear receptor ROR-alpha; Nuclear receptor RZR-alpha; Nuclear receptor subfamily 1 group F member 1; RAR-related orphan receptor A; Retinoid-related orphan receptor-alpha from Homo sapiens (Human) (see 24 papers)
NP_599023 nuclear receptor ROR-alpha isoform a from Homo sapiens
66% identity, 14% coverage

• function: Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target genes regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates genes involved in photoreceptor development including OPN1SW, OPN1SM and ARR3 and skeletal muscle development with MYOD1. Required for proper cerebellum development (PubMed:29656859). Regulates SHH gene expression, among others, to induce granule cells proliferation as well as expression of genes involved in calcium- mediated signal transduction. Regulates the circadian expression of several clock genes, including CLOCK, BMAL1, NPAS2 and CRY1. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1- mediated repression or RORA-mediated activation of clock genes expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Regulates genes involved in lipid metabolism such as apolipoproteins APOA1, APOA5, APOC3 and PPARG. In liver, has specific and redundant functions with RORC as positive or negative modulator of expression of genes encoding phase I and phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as CYP7B1 and SULT2A1. Induces a rhythmic expression of some of these genes. In addition, interplays functionally with NR1H2 and NR1H3 for the regulation of genes involved in cholesterol metabolism. Also involved in the regulation of hepatic glucose metabolism through the modulation of G6PC1 and PCK1. In adipose tissue, plays a role as negative regulator of adipocyte differentiation, probably acting through dual mechanisms. May suppress CEBPB-dependent adipogenesis through direct interaction and PPARG-dependent adipogenesis through competition for DNA-binding. Downstream of IL6 and TGFB and synergistically with RORC isoform 2, is implicated in the lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17- IL17F locus. Involved in hypoxia signaling by interacting with and activating the transcriptional activity of HIF1A. May inhibit cell growth in response to cellular stress. May exert an anti-inflammatory role by inducing CHUK expression and inhibiting NF-kappa-B signaling.
  subunit: Monomer. Interacts (via the DNA-binding domain) with HIF1A; the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interacts with CEBPB; the interaction disrupts the interaction CEBPB:EP300. Interacts with the coactivators NCOA2, PPARGC1A (via LXXLL motif), EP300 and MED1. Interacts with the corepressor NCOR1. Interacts with MAGED1 and CTNNB1. Interacts with CRY1 and PER2. Interacts (via AF-2 motif) with PROX1 (By similarity). Interacts with NRIP1. Isoform 4 interacts (via AF-2 motif) with isoform 1 of FOXP3 (via LXXLL motif).
• Linking genomic and proteomic signatures to brain amyloid burden: insights from GR@ACE/DEGESCO.
  Puerta, Functional & integrative genomics 2025
  • “...7,763,340 382 5.079 1.900E-07 GPC5 2262 P78333 13 92,050,929 93,519,490 275 4.956 3.604E-07 RORA 6095 P35398 15 60,780,483 61,521,518 185 4.827 6.948E-07 MACROD2 140,733 A1Z1Q3 20 13,976,015 16,033,842 354 4.787 8.471E-07 TMEM132D 121,256 Q14C87 12 129,556,270 130,388,211 205 4.759 9.717E-07 CDH13 1012 P55290 16 82,660,408 83,830,204...”
• Mechanism of Polygala-Acorus in Treating Autism Spectrum Disorder Based on Network Pharmacology and Molecular Docking
  Chen, Current computer-aided drug design 2024
  • “...APOA2 P02652 SRC P12931 PDE4D Q08499 CASP3 P42574 NR1I3 Q14994 KDR P35968 F10 P00742 RORA P35398 MAPK10 P53779 F2 P00734 MIF P14174 NR1H2 P55055 ITGAL P20701 IGF1R P08069 PGR P06401 KIF11 P52732 RXRA P19793 BACE1 P56817 MAOB P27338 NR3C2 P08235 DDX6 P26196 MAPK14 Q16539 CALM1 P0DP23...”
• Connecting genomic and proteomic signatures of amyloid burden in the brain.
  Puerta, medRxiv : the preprint server for health sciences 2024
  • “...7763340 382 5.079 1.900E-07 GPC5 2262 P78333 13 92050929 93519490 275 4.956 3.604E-07 RORA 6095 P35398 15 60780483 61521518 185 4.827 6.948E-07 MACROD2 140733 A1Z1Q3 20 13976015 16033842 354 4.787 8.471E-07 TMEM132D 121256 Q14C87 12 129556270 130388211 205 4.759 9.717E-07 CDH13 1012 P55290 16 82660408 83830204...”
• Elucidation of Short Linear Motif-Based Interactions of the FERM Domains of Ezrin, Radixin, Moesin, and Merlin.
  Ali, Biochemistry 2023
  • “...MSN P26038 NF2 P35240 NOP53 Q9NZM5 PAK6 Q9NQU5 PDCD6IP Q8WUM4 RDX P35241 RIMS1 Q86UR5 RORA P35398 RRBP1 Q9P2E9 TBX4 P57082 ZNF622 Q969S3 Protein Expression and Purification Expression constructs encoding the FERM domains of merlin, moesin, ezrin, and radixin were transformed into E. coli BL21(DE3). For expression,...”
• Uncovering the mechanism of Radix Paeoniae Alba in the treatment of restless legs syndrome based on network pharmacology and molecular docking
  Liu, Medicine 2022
  • “...0 PIK3CG Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform P48736 5 RORA Nuclear receptor ROR-alpha P35398 0 GSTP1 Glutathione S-transferase P1 P09211 10 AKR1B1 Aldo-keto reductase family 1 member B1 P15121 8 PDE5A cGMP-specific 3,5-cyclic phosphodiesterase O76074 3 AKT1 RAC-alpha serine/threonine-protein kinase P31749 28 AMY1C Alpha-amylase...”
• Glycyrrhetinic acid: A potential drug for the treatment of COVID-19 cytokine storm
  Li, Phytomedicine : international journal of phytotherapy and phytopharmacology 2022
  • “...Beta-secretase 1 27 P09917 ALOX5 Arachidonate 5-lipoxygenase 28 P30304 CDC25A Dual specificity phosphatase Cdc25A 29 P35398 RORA Nuclear receptor ROR-alpha 30 P27361 MAPK3 MAP kinase ERK1 31 Q01959 SLC6A3 Dopamine transporter 32 P29350 PTPN6 Protein-tyrosine phosphatase 1C 33 Q13133 NR1H3 LXR-alpha 34 P0DMS8 ADORA3 Adenosine A3...”
• Network pharmacology combined with GEO database identifying the mechanisms and molecular targets of Polygoni Cuspidati Rhizoma on Peri-implants
  Shan, Scientific reports 2022
  • “...Prostacyclin receptor PIGA P37287 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A FLT3 P36888 Receptor-type tyrosine-protein kinase FLT3 RORA P35398 Nuclear receptor ROR-alpha EPHX2 P34913 Bifunctional epoxide hydrolase 2 GABRA3 P34903 Gamma-aminobutyric acid receptor subunit alpha-3 CCR1 P32246 CC chemokine receptor type 1 SLC6A4 P31645 Sodium-dependent serotonin transporter WEE1 P30291...”
• Network Pharmacology-Based Strategy to Investigate the Mechanisms of Lenvatinib in the Treatment of Hepatocellular Carcinoma.
  Liu, Computational intelligence and neuroscience 2022
  • “...42 KCNN2 Small conductance calcium-activated potassium channel protein 2 Q9H2S1 43 RORA Nuclear receptor ROR-alpha P35398 44 GABRB3 Gamma-aminobutyric acid receptor subunit beta-3 P28472 45 EPHA2 Ephrin type-A receptor 2 P29317 Table 2 Binding energy values of the affinity of lenvatinib with the six selected core...”
• More
• The single-cell transcriptomic atlas and RORA-mediated 3D epigenomic remodeling in driving corneal epithelial differentiation.
  Li, Nature communications 2024
  • GeneRIF: The single-cell transcriptomic atlas and RORA-mediated 3D epigenomic remodeling in driving corneal epithelial differentiation.
• Retinoic acid related orphan receptor α is a genetic modifier that rescues retinal degeneration in a mouse model of Stargardt disease and Dry AMD.
  Akula, Gene therapy 2024
  • GeneRIF: Retinoic acid related orphan receptor alpha is a genetic modifier that rescues retinal degeneration in a mouse model of Stargardt disease and Dry AMD.
• Tumoral periprostatic adipose tissue exovesicles-derived miR-20a-5p regulates prostate cancer cell proliferation and inflammation through the RORA gene.
  Sánchez-Martin, Journal of translational medicine 2024
  • GeneRIF: Tumoral periprostatic adipose tissue exovesicles-derived miR-20a-5p regulates prostate cancer cell proliferation and inflammation through the RORA gene.
• Retinoic acid receptor-related orphan receptor alpha and synthetic RORα agonist against invasion and metastasis in tongue squamous cell carcinoma.
  Wang, Biochemical and biophysical research communications 2024 (PubMed)
  • GeneRIF: Retinoic acid receptor-related orphan receptor alpha and synthetic RORalpha agonist against invasion and metastasis in tongue squamous cell carcinoma.
• Novel Therapeutic Potential of Retinoid-Related Orphan Receptor α in Cardiovascular Diseases.
  Chen, International journal of molecular sciences 2023
  • GeneRIF: Novel Therapeutic Potential of Retinoid-Related Orphan Receptor alpha in Cardiovascular Diseases.
• Disturbed expression of vitamin D and retinoic acid-related orphan receptors α and γ and of megalin in inflammatory skin diseases.
  Brożyna, Experimental dermatology 2022
  • GeneRIF: Disturbed expression of vitamin D and retinoic acid-related orphan receptors alpha and gamma and of megalin in inflammatory skin diseases.
• Retinoid orphan nuclear receptor alpha (RORα) suppresses the epithelial-mesenchymal transition (EMT) by directly repressing Snail transcription.
  Xiong, The Journal of biological chemistry 2022
  • GeneRIF: Retinoid orphan nuclear receptor alpha (RORalpha) suppresses the epithelial-mesenchymal transition (EMT) by directly repressing Snail transcription.
• RORA polymorphisms are risk factors for allergic rhinitis susceptibility in the Shaanxi Han population.
  Lian, International immunopharmacology 2022 (PubMed)
  • GeneRIF: RORA polymorphisms are risk factors for allergic rhinitis susceptibility in the Shaanxi Han population.
• More

RORA_MOUSE / P51448 Nuclear receptor ROR-alpha; Nuclear receptor RZR-alpha; Nuclear receptor subfamily 1 group F member 1; RAR-related orphan receptor A; Retinoid-related orphan receptor-alpha from Mus musculus (Mouse) (see 21 papers)
66% identity, 14% coverage

• function: Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target genes regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates genes involved in photoreceptor development including OPN1SW, OPN1SM and ARR3 and skeletal muscle development with MYOD1. Required for proper cerebellum development, regulates SHH gene expression, among others, to induce granule cells proliferation as well as expression of genes involved in calcium-mediated signal transduction. Regulates the circadian expression of several clock genes, including CLOCK, BMAL1, NPAS2 and CRY1. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORA-mediated activation of clock genes expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Regulates genes involved in lipid metabolism such as apolipoproteins APOA1, APOA5, APOC3 and PPARG. In liver, has specific and redundant functions with RORC as positive or negative modulator of expression of genes encoding phase I and phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as CYP7B1 and SULT2A1. Induces a rhythmic expression of some of these genes. In addition, interplays functionally with NR1H2 and NR1H3 for the regulation of genes involved in cholesterol metabolism. Also involved in the regulation of hepatic glucose metabolism through the modulation of G6PC1 and PCK1. In adipose tissue, plays a role as negative regulator of adipocyte differentiation, probably acting through dual mechanisms. May suppress CEBPB-dependent adipogenesis through direct interaction and PPARG-dependent adipogenesis through competition for DNA-binding. Downstream of IL6 and TGFB and synergistically with RORC isoform 2, is implicated in the lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. Involved in hypoxia signaling by interacting with and activating the transcriptional activity of HIF1A. May inhibit cell growth in response to cellular stress. May exert an anti-inflammatory role by inducing CHUK expression and inhibiting NF-kappa-B signaling.
  subunit: Monomer. Interacts (via the DNA-binding domain) with HIF1A; the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interacts with CEBPB; the interaction disrupts the interaction CEBPB:EP300. Interacts with the coactivators NCOA2, PPARGC1A (via LXXLL motif), EP300 and MED1. Interacts with the corepressor NCOR1. Interacts with MAGED1 and CTNNB1. Interacts with CRY1 and PER2. Interacts (via AF-2 motif) with PROX1. Interacts with NRIP1. Isoform 4 interacts (via AF-2 motif) with isoform 1 of FOXP3 (via LXXLL motif) (By similarity).
• RNA sequencing indicates widespread conservation of circadian clocks in marine zooplankton
  Raghavan, NAR genomics and bioinformatics 2023
  • “...VRI (Dm Q9VMS4) Mm: NFIL3 (O08750) Mammalian REV-ERBa (Mm Q3UV55) Dm: EIP75B (P13055) RORa (Mm P51448) Dm: HR3 (P31396) Indicated in the left column are the baits, and in the right their counterparts. Alongside the protein name of the bait and the source organism, the sequences...”

NP_001276816 nuclear receptor ROR-alpha isoform 1 from Gallus gallus
66% identity, 14% coverage

• Effect of the melatonin nuclear receptor RORα on monochromatic light-induced T-lymphocyte proliferation in chicken thymus.
  Xiong, Immunology letters 2019 (PubMed)
  • GeneRIF: RORalpha could negatively regulate green light-enhanced T-lymphocyte proliferation in chick thymus by upregulating IkappaB phosphorylation, which promotes P65 nuclear translocation and NF-kappaB activation.

XP_022186162 hepatocyte nuclear factor 4-gamma isoform X3 from Nilaparvata lugens
55% identity, 16% coverage

• Effect of hepatocyte nuclear factor 4 on the fecundity of Nilaparvata lugens: Insights from RNA interference combined with transcriptomic analysis.
  Cheng, Genomics 2020 (PubMed)
  • GeneRIF: Effect of hepatocyte nuclear factor 4 on the fecundity of Nilaparvata lugens: Insights from RNA interference combined with transcriptomic analysis.

NP_991109 hepatic nuclear factor 4, beta from Danio rerio
55% identity, 16% coverage

• Conserved roles for Hnf4 family transcription factors in zebrafish development and intestinal function.
  Heppert, Genetics 2022
  • GeneRIF: Conserved roles for Hnf4 family transcription factors in zebrafish development and intestinal function.

HNF4A_HUMAN / P41235 Hepatocyte nuclear factor 4-alpha; HNF-4-alpha; Nuclear receptor subfamily 2 group A member 1; Transcription factor 14; TCF-14; Transcription factor HNF-4 from Homo sapiens (Human) (see 14 papers)
F1D8T1 Hepatocyte nuclear factor 4 4 alpha variant 2 from Homo sapiens
54% identity, 16% coverage

• function: Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes (PubMed:30597922). Activates the transcription of CYP2C38 (By similarity). Represses the CLOCK-BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698).
  subunit: Homodimerization is required for HNF4-alpha to bind to its recognition site (PubMed:14982928). Interacts with CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2 (PubMed:30530698). Interacts with NR0B2/SHP; the resulting heterodimer is transcriptionally inactive (PubMed:28128295). Interacts with DDX3X; this interaction disrupts the interaction between HNF4 and NR0B2 that forms inactive heterodimers and enhances the formation of active HNF4 homodimers (PubMed:28128295).
• A specific selenium-chelating peptide isolated from the protein hydrolysate of Grifola frondosa
  Xiong, RSC advances 2021
  • “...= Homo sapiens GN = PTTG1IP PE = 1 SV = 1 180 0.783099 0.039711 F1D8T1 Hepatocyte nuclear factor 4 4 alpha variant 2 OS = Homo sapiens GN = NR2A1 PE = 2 SV = 1 474 0.774468 0.016323 Q8NE01 Metal transporter CNNM3 OS =...”
• Impregnation of mesenchymal stem cell conditioned media with wortmannin enhanced its antiproliferative effect in breast cancer cells via PI3K/Akt/mTOR pathway
  Ismail, BMC research notes 2025
  • “...P30305 M-phase inducer phosphatase 2 0.975 P08173 Muscarinic acetylcholine receptor M4 0.939 Q00G26 Perilipin-5 0.925 P41235 Hepatocyte nuclear factor 4-alpha 0.902 P28566 5-hydroxytryptamine receptor 1E 0.877 P55211 Caspase-9 0.829 P04058 Acetylcholinesterase 0.822 O60240 Perilipin-1 0.763 P37058 Testosterone 17-beta-dehydrogenase 3 0.762 P04150 Glucocorticoid receptor 0.728 P31941 DNA...”
• A Network Pharmacology Method Combined with Molecular Docking Verification to Explore the Therapeutic Mechanisms Underlying Simiao Pill Herbal Medicine against Hyperuricemia
  Qian, BioMed research international 2023
  • “...P05091 37 NPPB P16860 77 G6PD P11413 38 HNF1A P20823 78 IL6R P08887 39 HNF4A P41235 79 IL18 Q14116 40 NFATC1 O95644 80 SLC6A3 Q01959 Table 2 Top 5 enriched BP, CC, and MF terms of GO enrichment analysis in this study. Ontology ID Description P...”
• Lung proteome and metabolome endotype in HIV-associated obstructive lung disease.
  Samorodnitsky, ERJ open research 2023
  • “...p - value Q - value Beclin-1 Q14457 8.960709 0.0001000 0.0035519 Hepatocyte nuclear factor 4- P41235 6.592431 0.0001000 0.0035519 Mothers against decapentaplegic homolog 3 P84022 6.590634 0.0001000 0.0035519 Ankyrin repeat domain-containing protein 1 Q15327 4.938720 0.0001000 0.0035519 Neurotrimin Q9P121 5.468840 0.0001000 0.0035519 Triple functional domain protein...”
• Exploring the protective effect of Sangggua Drink against type 2 diabetes mellitus in db/db mice using a network pharmacological approach and experimental validation.
  Cai, Heliyon 2023
• Transcriptional Inhibition of MicroRNA miR-122 by Small Molecules Reduces Hepatitis C Virus Replication in Liver Cells.
  Emanuelson, Journal of medicinal chemistry 2022
  • “...pE21 backbone containing the sequence of the ligand binding domain (aa 147377) of HNF4 (UniProt; P41235) with a C-terminal His tag was purchased from Twist Biosciences. The protein fragment was recombinantly expressed and purified from E. coli as described previously. 69 Purified HNF4 LBD (200 nM)...”
• Network Pharmacology-Based Prediction of Mechanism of Shenzhuo Formula for Application to DKD
  Wang, Evidence-based complementary and alternative medicine : eCAM 2021
  • “...receptor NR3C2 P08235 47 Cannabinoid receptor 1 CNR1 P21554 48 Hepatocyte nuclear factor 4-alpha HNF4A P41235 49 C-C chemokine receptor type 1 CCR1 P32246 50 Histone-lysine N-methyltransferase EZH2 EZH2 Q15910 Organism: Homo sapiens . Only 50 potential targets' information is shown here, and the whole is...”
  • “...receptor NR3C2 P08235 47 Cannabinoid receptor 1 CNR1 P21554 48 Hepatocyte nuclear factor 4-alpha HNF4A P41235 49 C-C chemokine receptor type 1 CCR1 P32246 50 Histone-lysine N-methyltransferase EZH2 EZH2 Q15910 51 MAP kinase p38 alpha MAPK14 Q16539 52 Bromodomain-containing protein 2 BRD2 P25440 53 Aldehyde dehydrogenase...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2021
  • “...Nomenclature Hepatocyte nuclear factor4 Hepatocyte nuclear factor4 Systematic nomenclature NR2A1 NR2A2 HGNC, UniProt HNF4A , P41235 HNF4G , Q14541 Endogenous agonists linoleic acid [ 163 ] Selective antagonists BI6015 [ 70 ] Comments HNF4 has constitutive transactivation activity [ 163 ] and binds DNA as a...”
• Identify Molecular Mechanisms of Jiangzhi Decoction on Nonalcoholic Fatty Liver Disease by Network Pharmacology Analysis and Experimental Validation.
  Wang, BioMed research international 2020
  • “...P01584 3553 IL1B Interleukin 1 beta 58 P05019 3479 IGF1 Insulin-like growth factor 1 59 P41235 3172 HNF4A Hepatocyte nuclear factor 4 alpha...”
• More

NP_599022 nuclear receptor ROR-alpha isoform b from Homo sapiens
66% identity, 13% coverage

• Expression and ecdysteroid responsiveness of the nuclear receptors HR3 and E75 in the crustacean Daphnia magna
  Hannas, Molecular and cellular endocrinology 2010
  • “...HR3 amino acid sequence to those of Drosophila melanogaster (DmHR3, ABN49269.2) and Homo sapiens (ROR, NP_599022). GenBank accession number follows gene name in parentheses. The putative DNA-binding C domain and ligand-binding E domain are underlined in the D. magna sequence. Shaded areas denote amino acid identity...”

XP_012719647 retinoic acid receptor RXR-alpha-A isoform X4 from Fundulus heteroclitus
57% identity, 15% coverage

• Tributyltin disrupts fin development in Fundulus heteroclitus from both PCB-sensitive and resistant populations: Investigations of potential interactions between AHR and PPARγ
  Crawford, Aquatic toxicology (Amsterdam, Netherlands) 2020
  • “...RXR and multiple forms of both RXR and RXR (Karchner and Hahn, unpublished analysis of XP_012719647; ( Baldwin et al., 2017 ). Rosiglitazone and TBT induce adiposity in zebrafish larvae ( Ouadah-Boussouf and Babin, 2016 ; Tingaud-Sequeira et al., 2011 ). In mammalian models, activation of...”

NP_001015557 hepatocyte nuclear factor 4-alpha isoform 2 from Bos taurus
54% identity, 16% coverage

• Tetra-primer ARMS-PCR identifies the novel genetic variations of bovine HNF-4α gene associating with growth traits.
  Wang, Gene 2014 (PubMed)
  • GeneRIF: Tetra-primer ARMS-PCR identifies the novel genetic variations of bovine HNF-4alpha gene associating with growth traits.
• Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and hepatocyte nuclear factor 4gamma (HNF-4gamma) and HNF-4alpha regulate the bovine growth hormone receptor 1A promoter through a common DNA element.
  Xu, Journal of molecular endocrinology 2004 (PubMed)
  • GeneRIF: Results show that chicken ovalbumin upstream promoter transcription factor II (COUP-TFII), hepatocyte nuclear factor 4alpha (HNF-4alpha) and HNF-4gamma regulate growth hormone receptor 1A promoter activity through binding to a common DNA element

U3J0G8 Retinoic acid receptor RXR from Anas platyrhynchos platyrhynchos
57% identity, 18% coverage

• Comparative proteomic analysis of pituitary glands from Huoyan geese between pre-laying and laying periods using an iTRAQ-based approach.
  Luan, PloS one 2017
  • “...subunit alpha isoform R0LLX0 1.27 hormone-mediated signalling pathway (GO:0009755) Progesterone receptor R0KDB7 1.48 Uncharacterized protein U3J0G8 RXRA 1.39 intracellular steroid hormone receptor signalling pathway (GO:0030518) Putative ATP-dependent RNA helicase DDX5 R0KA06 1.33 Protein DJ-1 R0KXC4 PARK7 1.27 neuropeptide signalling pathway (GO:0007218) Neurophysin 1 P35519 2.94 Neurophysin...”
  • “...synthetase R0JP63 1.24 steroid hormone mediated signalling pathway (GO:0043401) Progesterone receptor R0KDB7 1.48 Uncharacterized protein U3J0G8 RXRA 1.39 steroid metabolic process (GO:0008202) Apolipoprotein AI Q9PRR6 1.66 Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial R0K4R7 1.39 Aldehyde dehydrogenase family 1 member A3 R0LP44 1.26 Farnesyl pyrophosphate synthetase R0JP63 1.24 Wnt signalling...”

NP_620813 nuclear receptor subfamily 2 group F member 6 from Rattus norvegicus
62% identity, 18% coverage

• Cloning, expression and regulation of chicken ovalbumin upstream promoter transcription factors (COUP-TFII and EAR-2) in the rat anterior pituitary gland.
  Raccurt, Neuroendocrinology 2005 (PubMed)
  • GeneRIF: Cloning of rat pituitary COUP-TFII and EAR-2 genes, demonstrated that they are specifically expressed in lactotropes, and strongly suggested that they may play a role in modulating prolactin (PRL) gene expression during pregnancy.

RXR_LYMST / Q5I7G2 Retinoic acid receptor RXR; Retinoid X receptor; LymRXR from Lymnaea stagnalis (Great pond snail) (Helix stagnalis) (see paper)
55% identity, 17% coverage

• function: Ligand-dependent transcription factor probably involved in the retinoic acid response pathway. Binds 9-cis-retinoic acid (By similarity). Involved in embryo development, in particular eye and shell formation. May play a role in growth cone steering.
• Toxic Relationships: Prediction of TBT's Affinity to the Ecdysteroid Receptor of Triops longicaudatus
  Ferreira, Toxics 2023
  • “...T2MGI4.1.A Mollusca Biomphalaria glabrata UniProt A0A182ZWX8 A0A182ZWX8.1.A Crassostrea gigas UniProt K1PXX3 K1PXX3.1.A Lymnaea stagnalis UniProt Q5I7G2 Q8T5C6.1.A Mytilus edulis UniProt A0A8S3SHA1 A0A6J8CUS3.1.A Ostrea edulis NCBI XM_048899976 A0A6M2XXE3.1.A Physella acuta NCBI GHAL01006477 A0A433TMS9.1.A Rotifera Brachionus plicatilis UniProt A0A3M7RAV1 A0A221CB62.1.A toxics-11-00937-t002_Table 2 Table 2 Interaction residues between the...”
• Gene expression response of the non-target gastropod Physella acuta to Fenoxycarb, a juvenile hormone analog pesticide
  Caballero, Scientific reports 2023
  • “...77 87 OK474810 Retinoic acid receptor RXR 3551 435 Retinoic acid receptor RXR Lymnaea stagnalis Q5I7G2 96 97 DNA and protein size, homology, identity, and similarity are indicated. The contig number or accession number are indicated. Figure 1 HYPERLINK "sps:id::fig1||locator::gr1||MediaObject::0"Structure and conserved domains of the Physella...”
• Role of Transportome in the Gills of Chinese Mitten Crabs in Response to Salinity Change: A Meta-Analysis of RNA-Seq Datasets.
  Malik, Biology 2021
  • “...protein homolog) Q13336 Urea transporter 1 0.99 3.4321 10 6 Q5REW1 Iodotyrosine deiodinase 1 (IYD-1) Q5I7G2 Retinoic acid receptor RXR 0.99 3.4321 10 6 Q9Y535 DNA-directed RNA polymerase III subunit RPC8 Q5VWG9 Transcription initiation factor TFIID subunit 3 0.99 3.4321 10 6 Q04164 Putative epidermal cell...”

RORAA_DANRE / F1QLY4 Nuclear receptor ROR-alpha A; Retinoid-related orphan receptor alpha 2; Retinoid-related orphan receptor-alpha A from Danio rerio (Zebrafish) (Brachydanio rerio) (see 2 papers)
66% identity, 16% coverage

• function: Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) (By similarity). Required for proper cerebellum development (PubMed:29656859).
  disruption phenotype: Morpholino knockdown of the protein results in a reduced cerebellar area and smaller optic tecta area compared to control larvae. At 3 dpf, transgenic larvae present with a significantly decreased size of Purkinje and granule cell layers compared to controls.

NP_001037470 protein ultraspiracle homolog from Bombyx mori
58% identity, 16% coverage

• Transcriptomic analysis of the prothoracic gland from two lepidopteran insects, domesticated silkmoth Bombyx mori and wild silkmoth Antheraea pernyi
  Bian, Scientific reports 2019
  • “...Ecdysone receptor B ApPG.17239 ABS87644 [ Bombyx mori ] 83 2.6 BmPG.3587 12.87 Ultraspiracle ApPG.20814 NP_001037470 [ Bombyx mori ] 86 3.89 BmPG.2862 42.55 Juvenile hormone related genes Farnesyl diphosphate phosphatase ApPG.18455 NP_001040333 [ Bombyx mori ] 67 2.77 BmPG.4947 5.78 Aldehyde dehydrogenase (NAD+) ApPG.20532 XP_004931115...”
• Cloning and Expression of Ecdysone Receptor and Retinoid X Receptor from Procambarus clarkii: Induction by Eyestalk Ablation
  Dai, International journal of molecular sciences 2016
  • “...BAF75376), DamRXR from Daphnia magna (ABF74729), DmUSP from Drosophila melanogaster (NP_476781), BmUSP from Bombyx mori (NP_001037470), Dr RXR from Danio rerio RXR --A (NP_571292) and Hs RXR A from Homo sapiens (AAH63827). PcRXR1 , PcRXR4 and 18 RXR proteins from other species were involved in neighbor-joining...”
  • “...USP isoform-A (AAG24886), Apis mellifera USP isoform-A (AAF73057), Blattella germanica RXR (CAH69897), Bombyx mori USP (NP_001037470), Danio rerio RXR --A (NP_571292), Drosophila melanogaster USP (NP_476781), Homo sapiens RXR A (AAH63827), Macrobrachium nipponense RXR -L (KC460323), Marsupenaeus japonicus RXR (Accession Number: BAF75376), Mus musculus RXR 2 (AAB36777),...”

B6ZGT3 Hepatocyte nuclear factor 4, alpha from Homo sapiens
55% identity, 16% coverage

• Differential dimerization of variants linked to enhanced S-cone sensitivity syndrome (ESCS) located in the NR2E3 ligand-binding domain
  von, Human mutation 2015
  • “...(SwissProt Q9Y5x4, 410 aa) and NR2A1 (SwissProt B6ZGT3, 465 aa) amino acid sequences with Clustal W (www.ebi.ac.uk/Tools/msa/clustalw) and Clustal Omega...”

XP_419081 nuclear receptor subfamily 4 group A member 3 isoform X2 from Gallus gallus
61% identity, 12% coverage

• Schistosoma mansoni: identification of SmNR4A, a member of nuclear receptor subfamily 4
  Wu, Experimental parasitology 2008
  • “...( Bos Taurus NR4A2): NP_001069676 ; Chicken NR4A3 ( Gallus gallus (red jungle fowl) NR4A3): XP_419081 ; Drosophila HR38 ( D. melanogaster HR38): CAA61534 ; Drosophila FTZ-F1 ( Drosophila melanogaster fushi tarazu activator): AAA28542; Fish NOR1 ( Danio rerio (zebrafish) NOR1): XP_691396 ; Fish NR4A1 (...”

NP_001259163 hormone receptor 4, isoform K from Drosophila melanogaster
57% identity, 4% coverage

• Hormone receptor 4 is required in muscles and distinct ovarian cell types to regulate specific steps of Drosophila oogenesis.
  Weaver, Development (Cambridge, England) 2021
  • GeneRIF: Hormone receptor 4 is required in muscles and distinct ovarian cell types to regulate specific steps of Drosophila oogenesis.
• Early-late genes of the ecdysone cascade as models for transcriptional studies.
  Mazina, Cell cycle (Georgetown, Tex.) 2015
  • GeneRIF: DHR3 and Hr4 gene expression is dose dependent, is completely controlled by the hormone titer and decreases within hours of 20-hydroxyecdysone withdrawal.
• Function and dynamics of slam in furrow formation in early Drosophila embryo.
  Acharya, Developmental biology 2014 (PubMed)
  • GeneRIF: Following the onset of zygotic gene expression, Slam and Nullo together stabilise the retracting metaphase furrow and Slam triggers invagination of the cleavage furrow.
• Nuclear receptor DHR4 controls the timing of steroid hormone pulses during Drosophila development.
  Ou, PLoS biology 2011
  • GeneRIF: Nuclear receptor DHR4 controls the timing of steroid hormone pulses during Drosophila development
• Genomic mapping of binding regions for the Ecdysone receptor protein complex.
  Gauhar, Genome research 2009
  • GeneRIF: Results show that three direct targets of ECR/USP--hairy, vrille, and Hr4--are required for cellular differentiation in response to the hormone.

HR4_DROME / Q9W539 Hormone receptor 4; dHR4; Nuclear receptor subfamily 6 group A member 2 from Drosophila melanogaster (Fruit fly) (see paper)
57% identity, 5% coverage

• function: Coordinates growth and maturation by mediating endocrine responses to the attainment of critical weight during larval development. Plays a central role in the genetic cascades triggered by the steroid hormone ecdysone at the onset of metamorphosis, acting as both a repressor of the early ecdysone-induced regulatory genes and an inducer of the ftz-f1 midprepupal competence factor.
  disruption phenotype: Flies exhibit larvae that precociously leave the food to form premature prepupae, resulting in abbreviated larval development that translates directly into smaller and lighter animals.

NP_001318085 hepatocyte nuclear factor 4-gamma isoform 2 from Danio rerio
55% identity, 17% coverage

• Conserved roles for Hnf4 family transcription factors in zebrafish development and intestinal function.
  Heppert, Genetics 2022
  • GeneRIF: Conserved roles for Hnf4 family transcription factors in zebrafish development and intestinal function.

K1PXX3 RXR1 retinoid X receptor isoform 1 from Magallana gigas
55% identity, 17% coverage

• Toxic Relationships: Prediction of TBT's Affinity to the Ecdysteroid Receptor of Triops longicaudatus.
  Ferreira, Toxics 2023
  • “...Cnidaria Hydra vulgaris UniProt A0A8B7EC76 T2MGI4.1.A Mollusca Biomphalaria glabrata UniProt A0A182ZWX8 A0A182ZWX8.1.A Crassostrea gigas UniProt K1PXX3 K1PXX3.1.A Lymnaea stagnalis UniProt Q5I7G2 Q8T5C6.1.A Mytilus edulis UniProt A0A8S3SHA1 A0A6J8CUS3.1.A Ostrea edulis NCBI XM_048899976 A0A6M2XXE3.1.A Physella acuta NCBI GHAL01006477 A0A433TMS9.1.A Rotifera Brachionus plicatilis UniProt A0A3M7RAV1 A0A221CB62.1.A toxics-11-00937-t002_Table 2 Table...”

NP_001274112 hepatocyte nuclear factor 4-alpha isoform 9 from Homo sapiens
54% identity, 16% coverage

• Insulin Determines Transforming Growth Factor β Effects on Hepatocyte Nuclear Factor 4α Transcription in Hepatocytes.
  Feng, The American journal of pathology 2024 (PubMed)
  • GeneRIF: Insulin Determines Transforming Growth Factor beta Effects on Hepatocyte Nuclear Factor 4alpha Transcription in Hepatocytes.
• Association between HNF4A rs1800961 polymorphisms and gallstones in a Taiwanese population.
  Lin, Journal of gastroenterology and hepatology 2024 (PubMed)
  • GeneRIF: Association between HNF4A rs1800961 polymorphisms and gallstones in a Taiwanese population.
• TRIB3-TRIM8 complex drives NAFLD progression by regulating HNF4α stability.
  Xiao, Journal of hepatology 2024 (PubMed)
  • GeneRIF: TRIB3-TRIM8 complex drives NAFLD progression by regulating HNF4alpha stability.
• Functional characterization of HNF4A gene variants identify promoter and cell line specific transactivation effects.
  Kaci, Human molecular genetics 2024
  • GeneRIF: Functional characterization of HNF4A gene variants identify promoter and cell line specific transactivation effects.
• Krüppel-like factor 10 protects against metabolic dysfunction-associated steatohepatitis by regulating HNF4α-mediated metabolic pathways.
  Pan, Metabolism: clinical and experimental 2024
  • GeneRIF: Kruppel-like factor 10 protects against metabolic dysfunction-associated steatohepatitis by regulating HNF4alpha-mediated metabolic pathways.
• Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.
  Ehle, Communications biology 2024
  • GeneRIF: Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.
• Abrogating K458 acetylation enhances hepatocyte nuclear factor 4α (HNF4α)-induced differentiation therapy for hepatocellular carcinoma.
  Liu, Journal of digestive diseases 2024 (PubMed)
  • GeneRIF: Abrogating K458 acetylation enhances hepatocyte nuclear factor 4alpha (HNF4alpha)-induced differentiation therapy for hepatocellular carcinoma.
• Molecular mechanism of HNF-1A-mediated HNF4A gene regulation and promoter-driven HNF4A-MODY diabetes.
  Kind, JCI insight 2024
  • GeneRIF: Molecular mechanism of HNF-1A-mediated HNF4A gene regulation and promoter-driven HNF4A-MODY diabetes.
• More

RXR_BIOGL / Q8T5C6 Retinoic acid receptor RXR; RXR-like protein; Retinoid X receptor; BgRXR from Biomphalaria glabrata (Bloodfluke planorb) (Freshwater snail) (see 2 papers)
55% identity, 17% coverage

• function: Ligand-dependent transcription factor probably involved in the retinoic acid response pathway. Binds 9-cis-retinoic acid (9C-RA) and, to a lesser extent, docosahexaenoic acid (DHA), phytanic acid, methoprene acid and oleic acid. Binds to double-stranded DNA sequences containing direct repeats (DR) with the consensus sequence 5'- [AG]GGTCA-3' and 1, 2, 3, 4 or 5 nucleotides in between (DR1, DR2, DR3. DR4 and DR5, respectively). Binding to DR1 is strongest. Transactivates gene expression when 9C-RA or DHA is bound.
  subunit: Homodimer (via ligand-binding domain). Heterodimer (Probable). Homotetramer consisting of 2 canonical homodimers. Within the tetramer, each monomer binds one molecule of 9C-RA and a NCOA1-derived peptide containing an L-X(2)-L-L motif (Probable).

rxr / CAH69897.1 retinoid X receptor from Blattella germanica (see paper)
58% identity, 18% coverage

RXRGB_DANRE / Q6DHP9 Retinoic acid receptor RXR-gamma-B; Nuclear receptor subfamily 2 group B member 3-B; Retinoid X receptor gamma-B from Danio rerio (Zebrafish) (Brachydanio rerio) (see paper)
58% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for rxrs is 9-cis retinoic acid (By similarity).
  subunit: Homodimer. Heterodimer; with a rar molecule. Binds DNA preferentially as a rar/rxr heterodimer.

NP_001107766 ultraspiracle nuclear receptor from Tribolium castaneum
57% identity, 18% coverage

• Structural and functional characterization of a novel type of ligand-independent RXR-USP receptor.
  Iwema, The EMBO journal 2007
  • GeneRIF: Data demonstrate that TcUSP is a constitutively silent partner of the ecdysone receptor, and that none of the RXR ligands can bind and activate TcUSP.

A1JUG2 Ultraspiracle nuclear receptor from Tribolium castaneum
57% identity, 18% coverage

• Satellite DNA-like elements associated with genes within euchromatin of the beetle Tribolium castaneum
  Brajković, G3 (Bethesda, Md.) 2012
  • “...Transposon 894 A3RE80 658661 Cardioacceleratory peptide receptor 5 66 3 27,105 Q868T3 FBgn0039396 Transposon 894 A1JUG2 661207 Ultraspiracle 5 67 Inside P20153 FBgn0003964 Satellite 379 1.1 D6WNB3 656063 Y box protein 5 68 5 14,993 O46173 FBgn0022959 Satellite 455 1.3 D6WNB6 656095 Peptide chain release factor...”

NP_001037042 nuclear hormone receptor E75 isoform C from Bombyx mori
62% identity, 10% coverage

• Identification of two juvenile hormone inducible transcription factors from the silkworm, Bombyx mori.
  Matsumoto, Journal of insect physiology 2015 (PubMed)
  • GeneRIF: Expression of E75 and Enhancer of split mbeta(E(spl)mbeta) was induced by juvenile hormone I.

XP_049315305 ecdysone-induced protein 75B, isoforms C/D isoform X1 from Bactrocera dorsalis
62% identity, 5% coverage

• MicroRNA Let-7 targets the ecdysone signaling pathway E75 gene to control larval-pupal development in Bactrocera dorsalis.
  Peng, Insect science 2019 (PubMed)
  • GeneRIF: Let-7 regulates the ecdysone signaling pathway through the exact dose of E75 gene, and is indispensable for normal larval-pupal development.

e75C / CAL36975.1 ecdysone-induced protein 75C from Aedes aegypti (see paper)
62% identity, 6% coverage

XP_021704146 ecdysone-inducible protein E75 isoform X1 from Aedes aegypti
62% identity, 6% coverage

• Juvenile hormone regulation of microRNAs is mediated by E75 in the Dengue vector mosquito Aedes aegypti.
  Aksoy, Proceedings of the National Academy of Sciences of the United States of America 2021
  • GeneRIF: Juvenile hormone regulation of microRNAs is mediated by E75 in the Dengue vector mosquito Aedes aegypti.

XP_066909975 nuclear receptor subfamily 4 group A member 3 from Equus caballus
61% identity, 12% coverage

• A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse.
  Rosengren, Nature genetics 2008 (PubMed)
  • GeneRIF: Both STX17 and the neighboring NR4A3 gene are overexpressed in melanomas from Gray horses.

XP_005673010 hepatocyte nuclear factor 4-alpha isoform X3 from Sus scrofa
54% identity, 16% coverage

• Characterization of a putative cis-regulatory element that controls transcriptional activity of the pig uroplakin II gene promoter.
  Kwon, Biochemical and biophysical research communications 2011 (PubMed)
  • GeneRIF: HNF4 positively regulates pUPII gene promoter activity.

NP_775292 nuclear receptor subfamily 4 group A member 3 isoform b from Homo sapiens
61% identity, 12% coverage

• Upregulation of NOR-1 in calcified human vascular tissues: impact on osteogenic differentiation and calcification.
  Ballester-Servera, Translational research : the journal of laboratory and clinical medicine 2024 (PubMed)
  • GeneRIF: Upregulation of NOR-1 in calcified human vascular tissues: impact on osteogenic differentiation and calcification.
• RP11-495P10.1 promotes HCC cell proliferation by regulating reprogramming of glucose metabolism and acetylation of the NR4A3 promoter via the PDK1/PDH axis.
  Liu, Acta biochimica et biophysica Sinica 2024
  • GeneRIF: RP11-495P10.1 promotes HCC cell proliferation by regulating reprogramming of glucose metabolism and acetylation of the NR4A3 promoter via the PDK1/PDH axis.
• Potential Roles of Nr4a3-Mediated Inflammation in Immunological and Neurological Diseases.
  He, Molecular neurobiology 2024 (PubMed)
  • GeneRIF: Potential Roles of Nr4a3-Mediated Inflammation in Immunological and Neurological Diseases.
• Orphan Nuclear Receptor Family 4A (NR4A) Members NR4A2 and NR4A3 Selectively Modulate Elements of the Monocyte Response to Buffered Hypercapnia.
  Phelan, International journal of molecular sciences 2024
  • GeneRIF: Orphan Nuclear Receptor Family 4A (NR4A) Members NR4A2 and NR4A3 Selectively Modulate Elements of the Monocyte Response to Buffered Hypercapnia.
• Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation.
  Ma, Circulation research 2024 (PubMed)
  • GeneRIF: Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation.
• NOR1 promotes the osteoblastic differentiation of human periodontal ligament stem cells via TGF-β signaling pathway.
  Wu, Cellular and molecular life sciences : CMLS 2024
  • GeneRIF: NOR1 promotes the osteoblastic differentiation of human periodontal ligament stem cells via TGF-beta signaling pathway.
• A minority of cases of acinic cell carcinoma of the salivary glands are driven by an NR4A2 rearrangement: the diagnostic utility of the assessment of NR4A2 and NR4A3 alterations in salivary gland tumors.
  Klubíčková, Virchows Archiv : an international journal of pathology 2023 (PubMed)
  • GeneRIF: A minority of cases of acinic cell carcinoma of the salivary glands are driven by an NR4A2 rearrangement: the diagnostic utility of the assessment of NR4A2 and NR4A3 alterations in salivary gland tumors.
• Nuclear Receptor Subfamily 4A Signaling as a Key Disease Pathway of CD1c+ Dendritic Cell Dysregulation in Systemic Sclerosis.
  Servaas, Arthritis & rheumatology (Hoboken, N.J.) 2023
  • GeneRIF: Nuclear Receptor Subfamily 4A Signaling as a Key Disease Pathway of CD1c+ Dendritic Cell Dysregulation in Systemic Sclerosis.
• More

XP_045228490 nuclear receptor subfamily 4 group A member 3 isoform X2 from Macaca fascicularis
61% identity, 12% coverage

• SMARCB1 Promotes Ubiquitination and Degradation of NR4A3 via Direct Interaction Driven by ROS in Vascular Endothelial Cell Injury.
  Lu, Oxidative medicine and cellular longevity 2020
  • GeneRIF: SMARCB1 Promotes Ubiquitination and Degradation of NR4A3 via Direct Interaction Driven by ROS in Vascular Endothelial Cell Injury.

NR4A3_HUMAN / Q92570 Nuclear receptor subfamily 4 group A member 3; Mitogen-induced nuclear orphan receptor; Neuron-derived orphan receptor 1; Nuclear hormone receptor NOR-1 from Homo sapiens (Human) (see 4 papers)
61% identity, 12% coverage

• function: Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner. Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (By similarity). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site (By similarity). Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A (By similarity). Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development (By similarity). Also mediates survival of neuron and smooth muscle cells; mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription (By similarity). Also plays a role in inflammation; upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site (By similarity) (PubMed:20558821). In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation (By similarity). Also plays a role in metabolism; by modulating feeding behavior; and by playing a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP- glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1. Upon catecholamines stimulation, regulates gene expression that controls oxidative metabolism in skeletal muscle (By similarity). Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface (PubMed:24022864). Finally, during gastrulation plays a crucial role in the formation of anterior mesoderm by controlling cell migration. Inhibits adipogenesis (By similarity). Also participates in cardiac hypertrophy by activating PARP1 (By similarity).
  subunit: Interacts with SIX3 (via homeobox); differentially regulates the transcriptional activities of NR4A3 (PubMed:12543801). Interacts with the constituents of DNA-PK heterotrimer PRKDC, XRCC6 and XRCC5; phosphorylates and prevents NR4A3 ubiquitinylation and degradation (PubMed:25852083). Interacts with NCOA2; potentiates the activity of the NR4A3. Interacts with NCOA1, NCOA3, MED1 and KAT2B. Interacts with EP300 and NCOA2; mediates the recruitment of MED1 in the coactivator complex (By similarity). Interacts with NR3C1 (via nuclear receptor DNA-binding domain); the interactions represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE). Interacts with TRIM28; the interactions potentiates NR4A3 activity on NurRE promoter. Binds DNA as a monomer and homodimer. Interacts with PARP1; activates PARP1 by improving acetylation of PARP1 and suppressing the interaction between PARP1 and SIRT1 (By similarity).
• THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2021
  • “...Systematic nomenclature NR4A1 NR4A2 NR4A3 HGNC, UniProt NR4A1 , P22736 NR4A2 , P43354 NR4A3 , Q92570 Comments An endogenous agonist, cytosporone B , has been described [ 164 ], although structural analysis and molecular modelling has not identified a ligand binding site [ 4 , 39...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2017
  • “...Systematic nomenclature NR4A1 NR4A2 NR4A3 HGNC, UniProt NR4A1 , P22736 NR4A2 , P43354 NR4A3 , Q92570 Comments An endogenous agonist, cytosporone B , has been described [ 164 ], although structural analysis and molecular modelling has not identified a ligand binding site [ 4 , 40...”
• The Concise Guide to PHARMACOLOGY 2015/16: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2015
  • “...Systematic nomenclature NR4A1 NR4A2 NR4A3 HGNC, UniProt NR4A1 , P22736 NR4A2 , P43354 NR4A3 , Q92570 Comments An endogenous agonist, cytosporone B , has been described [ 168 ], although structural analysis and molecular modelling has not identified a ligand binding site [ 4 , 40...”
• The Concise Guide to PHARMACOLOGY 2013/14: nuclear hormone receptors
  Alexander, British journal of pharmacology 2013
  • “...orphan receptor 1 Systematic nomenclature NR4A1 NR4A2 NR4A3 HGNC, UniProt NR4A1, P22736 NR4A2, P43354 NR4A3, Q92570 Comment An endogenous agonist, cytosporone B, has been described 113 , although structural analysis and molecular modelling has not identified a ligand binding site 109 , 111 , 112 Further...”

Q4H3D5 Nuclear receptor from Ciona intestinalis
54% identity, 14% coverage

• A new protein linear motif benchmark for multiple sequence alignment software.
  Perrodou, BMC bioinformatics 2008
  • “...is defined as a 'false negative', since it can be aligned unambiguously with other sequences (Q4H3D5 and Q3UP48) that do match the ELM regular expression. Sequences that do not contain any matches to the ELM regular expression and that cannot be aligned manually in the region...”

rxr / CAH69898.1 retinoid X receptor from Blattella germanica (see paper)
58% identity, 17% coverage

e75A / CAL36974.1 ecdysone-induced protein 75A from Aedes aegypti (see paper)
62% identity, 7% coverage

RXRBA_DANRE / Q7SYN5 Retinoic acid receptor RXR-beta-A; Nuclear receptor subfamily 2 group B member 2-A; Retinoid X receptor beta-A from Danio rerio (Zebrafish) (Brachydanio rerio) (see 2 papers)
55% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for rxrs is 9-cis retinoic acid (By similarity).
  subunit: Homodimer (By similarity). Heterodimer; with a rar molecule (By similarity). Binds DNA preferentially as a rar/rxr heterodimer (By similarity). Heterodimerizes with rarga.

RXRAB_DANRE / Q90415 Retinoic acid receptor RXR-alpha-B; Nuclear receptor subfamily 2 group B member 1-B; Retinoid X receptor alpha-B from Danio rerio (Zebrafish) (Brachydanio rerio) (see 4 papers)
57% identity, 20% coverage

• function: Receptor for retinoic acid that acts as a transcription factor (PubMed:7565671). Forms homo- or heterodimers with retinoic acid receptors (rars) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes (By similarity). The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (By similarity). The high affinity ligand for rxrs is 9- cis retinoic acid (By similarity). In the absence of ligand, the rar/rxr heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (By similarity). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (By similarity).
  subunit: Homodimer. Heterodimer; with a rar molecule. Binds DNA preferentially as a rar/rxr heterodimer.

HNF4A_MOUSE / P49698 Hepatocyte nuclear factor 4-alpha; HNF-4-alpha; Nuclear receptor subfamily 2 group A member 1; Transcription factor 14; TCF-14; Transcription factor HNF-4 from Mus musculus (Mouse) (see 5 papers)
54% identity, 16% coverage

• function: Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitatating the recruitment of RNA pol II to the promoters of target genes (By similarity). Activates the transcription of CYP2C38 (PubMed:30555544). Represses the CLOCK-BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698).
  subunit: Homodimerization is required for HNF4-alpha to bind to its recognition site (By similarity). Interacts with CLOCK, BMAL1 and PER1 (By similarity). Interacts with PER2 (PubMed:20159955). Interacts with CRY1 and CRY2 (PubMed:28751364). Interacts with NR0B2/SHP; the resulting heterodimer is transcriptionally inactive (By similarity). Interacts with DDX3X; this interaction disrupts the interaction between HNF4 and NR0B2 that forms inactive heterodimers and enhances the formation of active HNF4 homodimers (By similarity).
  disruption phenotype: Pancreatic beta-cells-specific knockout results in hyperinsulinemia and hypoglycemia.
• Deletion of the Mitochondrial Protein VWA8 Induces Oxidative Stress and an HNF4α Compensatory Response in Hepatocytes.
  Luo, Biochemistry 2019
  • “...the proteomics experiments are given in Table S5 . Protein Uniprot ID VWA8 Q8CC88 HNF4a P49698 Cyp4a12a Q91WL5 Adh1 P00329 Pipox Q9D826 Pxmp4 Q9JJW0 Phyh Q35386 Pex11a Q9Z211 Decr2 Q9W768 Ehhadh Q9BBM2 Pxmp2 P42925 Acot4 Q8BWN8 Acaa2 Q8BWT1 Hadh Q61425 Acot1 O55137 Acadm P45952 Mtp O08601...”

XP_012548317 protein ultraspiracle homolog isoform X2 from Bombyx mori
58% identity, 18% coverage

• The expression profile and promoter analysis of ultraspiracle gene in the silkworm Bombyx mori.
  Huang, Molecular biology reports 2014 (PubMed)
  • GeneRIF: BmUSP is expressed at different levels in different tissues of the silkworm, but all are subjected to the regulation by ecdysone.
• Ecdysone receptor and ultraspiracle proteins are tyrosine phosphorylated during adult development of silkmoths.
  Sridhara, Insect biochemistry and molecular biology 2012 (PubMed)
  • GeneRIF: tyrosine phosphorylated coincidental with high protein tyrosine phosphorylations during growth to differentiation transition
• Silkworm 30K protein inhibits ecdysone-induced apoptosis by blocking the binding of ultraspiracle to ecdysone receptor-B1 in cultured Bm5 cells.
  Kim, Archives of insect biochemistry and physiology 2012 (PubMed)
  • GeneRIF: 30K proteins bound primarily to the EcR-B1 and not to ultraspiracle.

RXRGA_DANRE / Q90416 Retinoic acid receptor RXR-gamma-A; Nuclear receptor subfamily 2 group B member 3-A; Retinoic acid receptor RXR-alpha; Retinoid X receptor alpha; Retinoid X receptor gamma-A from Danio rerio (Zebrafish) (Brachydanio rerio) (see 3 papers)
58% identity, 17% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for rxrs is 9-cis retinoic acid (By similarity).
  subunit: Homodimer (By similarity). Heterodimer; with a rar molecule (By similarity). Binds DNA preferentially as a rar/rxr heterodimer (By similarity). Heterodimerizes with rarga.

NP_571292 retinoic acid receptor RXR-gamma-A from Danio rerio
58% identity, 17% coverage

• Retinoid X receptor alpha is a spatiotemporally predominant therapeutic target for anthracycline-induced cardiotoxicity.
  Ma, Science advances 2020
  • GeneRIF: Retinoid X receptor alpha is a spatiotemporally predominant therapeutic target for anthracycline-induced cardiotoxicity.
• Cloning and Expression of Ecdysone Receptor and Retinoid X Receptor from Procambarus clarkii: Induction by Eyestalk Ablation
  Dai, International journal of molecular sciences 2016
  • “...Drosophila melanogaster (NP_476781), BmUSP from Bombyx mori (NP_001037470), Dr RXR from Danio rerio RXR --A (NP_571292) and Hs RXR A from Homo sapiens (AAH63827). PcRXR1 , PcRXR4 and 18 RXR proteins from other species were involved in neighbor-joining tree construction, their names and the accession numbers...”
  • “...USP isoform-A (AAF73057), Blattella germanica RXR (CAH69897), Bombyx mori USP (NP_001037470), Danio rerio RXR --A (NP_571292), Drosophila melanogaster USP (NP_476781), Homo sapiens RXR A (AAH63827), Macrobrachium nipponense RXR -L (KC460323), Marsupenaeus japonicus RXR (Accession Number: BAF75376), Mus musculus RXR 2 (AAB36777), Tenebrio molitor USP protein (CAB75361),...”
• Plasticity of photoreceptor-generating retinal progenitors revealed by prolonged retinoic acid exposure.
  Stevens, BMC developmental biology 2011
  • GeneRIF: The RA receptors RXR gamma and RAR alpha-b are expressed in patterns consistent with mediating the effects of RA on photoreceptors.

HNF4A_RAT / P22449 Hepatocyte nuclear factor 4-alpha; HNF-4-alpha; Nuclear receptor subfamily 2 group A member 1; Transcription factor 14; TCF-14; Transcription factor HNF-4 from Rattus norvegicus (Rat) (see 2 papers)
54% identity, 16% coverage

• function: Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes (By similarity). Activates the transcription of CYP2C38 (By similarity). Represses the CLOCK-BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (By similarity).
  subunit: Homodimerization is required for HNF4-alpha to bind to its recognition site (PubMed:12193589). Interacts with CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2 (By similarity). Interacts with NR0B2/SHP; the resulting heterodimer is transcriptionally inactive (By similarity). Interacts with DDX3X; this interaction disrupts the interaction between HNF4 and NR0B2 that forms inactive heterodimers and enhances the formation of active HNF4 homodimers (By similarity).

NR4A3_MOUSE / Q9QZB6 Nuclear receptor subfamily 4 group A member 3; Orphan nuclear receptor TEC; Translocated in extraskeletal chondrosarcoma from Mus musculus (Mouse) (see 14 papers)
XP_006537719 nuclear receptor subfamily 4 group A member 3 isoform X1 from Mus musculus
61% identity, 12% coverage

• function: Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner (PubMed:12709428). Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (By similarity). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site (PubMed:21868379). Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A (By similarity). Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner (PubMed:24806827). During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development (PubMed:11784868). Also mediates survival of neuron and smooth muscle cells; mediates CREB- induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance (PubMed:15456880, PubMed:20566846). Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription (PubMed:19153266). Also plays a role in inflammation; upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site (PubMed:20558821). In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation (PubMed:24586680). Also plays a role in metabolism; by modulating feeding behavior; and by playing a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP- glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1 (PubMed:19523439, PubMed:23897430). Upon catecholamines stimulation, regulates gene expression that controls oxidative metabolism in skeletal muscle (PubMed:18325999). Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface (By similarity). Finally, during gastrulation plays a crucial role in the formation of anterior mesoderm by controlling cell migration (PubMed:13129926). Inhibits adipogenesis (PubMed:18945812). Also participates in cardiac hypertrophy by activating PARP1 (By similarity).
  subunit: Interacts with SIX3 (via homeobox); differentially regulates the transcriptional activities of NR4A3. Interacts with NCOA2; potentiates the activity of the NR4A3 (PubMed:12709428). Interacts with NCOA1, NCOA3, MED1 and KAT2B. Interacts with EP300 and NCOA2; mediates the recruitment of MED1 in the coactivator complex (PubMed:12709428). Interacts with the constituents of DNA-PK heterotrimer PRKDC, XRCC6 and XRCC5; phosphorylates and prevents NR4A3 ubiquitinylation and degradation (By similarity). Interacts with NR3C1 (via nuclear receptor DNA-binding domain); the interactions represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE). Interacts with TRIM28; the interactions potentiates NR4A3 activity on NurRE promoter. Binds DNA as a monomer and homodimer. Interacts with PARP1; activates PARP1 by improving acetylation of PARP1 and suppressing the interaction between PARP1 and SIRT1 (By similarity).
  disruption phenotype: Nr4a3 homozygous knockout mice are viable and normal in appearance; however, abnormal hyperactive and partial bidirectional circling behavior is observed by 3 weeks of age in 15% of these mice. The circling behavior is interspersed with noncircling periods of feeding, grooming, and sleep (PubMed:11784868). A small percentage of adult Nr4a3 homozygotes displayes brief freezing spells with tonic posturing that are exacerbated with handling (PubMed:15456880). The overall food consumption of Nr4a3 homozygous knockout mice is higher. Moreover, Nr4a3 homozygous mice lose more body weight upon fasting but clearly consumed more food during refeeding. By the end of the fasting period, Nr4a3 homozygous mice display signs of exhaustion (PubMed:23897430). Nr4a3 homozygous leads to embryonic lethality around 8.5 dpc (PubMed:13129926).
• Glucose may Contribute to Retrieval and Reconsolidation of Contextual Fear Memory Through Hippocampal Nr4a3 and Bdnf mRNA Expression and May Act Synergically with Adrenaline.
  Oliveira, Molecular neurobiology 2024
  • GeneRIF: Glucose may Contribute to Retrieval and Reconsolidation of Contextual Fear Memory Through Hippocampal Nr4a3 and Bdnf mRNA Expression and May Act Synergically with Adrenaline.
• Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation.
  Ma, Circulation research 2024 (PubMed)
  • GeneRIF: Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation.
• High NOR-1 (Neuron-Derived Orphan Receptor 1) Expression Strengthens the Vascular Wall Response to Angiotensin II Leading to Aneurysm Formation in Mice.
  Cañes, Hypertension (Dallas, Tex. : 1979) 2021 (PubMed)
  • GeneRIF: High NOR-1 (Neuron-Derived Orphan Receptor 1) Expression Strengthens the Vascular Wall Response to Angiotensin II Leading to Aneurysm Formation in Mice.
• NR4A3: A Key Nuclear Receptor in Vascular Biology, Cardiovascular Remodeling, and Beyond.
  Martínez-González, International journal of molecular sciences 2021
  • GeneRIF: NR4A3: A Key Nuclear Receptor in Vascular Biology, Cardiovascular Remodeling, and Beyond.
• Neuron-derived orphan receptor-1 modulates cardiac gene expression and exacerbates angiotensin II-induced cardiac hypertrophy.
  Cañes, Clinical science (London, England : 1979) 2020 (PubMed)
  • GeneRIF: NOR-1 is involved in the transcriptional programme leading to Hypertensive cardiac hypertrophy.
• miR‑106b‑5p modulates acute pulmonary embolism via NOR1 in pulmonary artery smooth muscle cells.
  Chen, International journal of molecular medicine 2020
  • GeneRIF: miR106b5p modulates acute pulmonary embolism via NOR1 in pulmonary artery smooth muscle cells.
• Negative Regulation of Tec Kinase Alleviates LPS-Induced Acute Kidney Injury in Mice via theTLR4/NF-κB Signaling Pathway.
  Zhang, BioMed research international 2020
  • GeneRIF: Negative Regulation of Tec Kinase Alleviates LPS-Induced Acute Kidney Injury in Mice via theTLR4/NF-kappaB Signaling Pathway.
• Early programming of CD8+ T cell response by the orphan nuclear receptor NR4A3.
  Odagiu, Proceedings of the National Academy of Sciences of the United States of America 2020
  • GeneRIF: Early programming of CD8(+) T cell response by the orphan nuclear receptor NR4A3.
• More
• Nur77 is phosphorylated in cells by RSK in response to mitogenic stimulation.
  Wingate, The Biochemical journal 2006

SHR2_STRPU / Q26622 Orphan steroid hormone receptor 2; SpSHR2 from Strongylocentrotus purpuratus (Purple sea urchin) (see 3 papers)
62% identity, 12% coverage

• function: Orphan nuclear receptor. Binds to the hormone response element in the upstream promoter region of the CYIIIB gene in vitro. Both isoform 1 and isoform 2 bind DNA.
  subunit: Binds DNA as a monomer.

XP_006498851 hepatocyte nuclear factor 4-alpha isoform X2 from Mus musculus
54% identity, 16% coverage

• TRIB3-TRIM8 complex drives NAFLD progression by regulating HNF4α stability.
  Xiao, Journal of hepatology 2024 (PubMed)
  • GeneRIF: TRIB3-TRIM8 complex drives NAFLD progression by regulating HNF4alpha stability.
• HNF4α ubiquitination mediated by Peli1 impairs FAO and accelerates pressure overload-induced myocardial hypertrophy.
  Hou, Cell death & disease 2024
  • GeneRIF: HNF4alpha ubiquitination mediated by Peli1 impairs FAO and accelerates pressure overload-induced myocardial hypertrophy.
• Krüppel-like factor 10 protects against metabolic dysfunction-associated steatohepatitis by regulating HNF4α-mediated metabolic pathways.
  Pan, Metabolism: clinical and experimental 2024
  • GeneRIF: Kruppel-like factor 10 protects against metabolic dysfunction-associated steatohepatitis by regulating HNF4alpha-mediated metabolic pathways.
• A MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin.
  Gu, Nature communications 2024
  • GeneRIF: A MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin.
• Dynamic RNA polymerase II occupancy drives differentiation of the intestine under the direction of HNF4.
  Vemuri, Cell reports 2024
  • GeneRIF: Dynamic RNA polymerase II occupancy drives differentiation of the intestine under the direction of HNF4.
• HNF4α is required for Tkfc promoter activation by ChREBP.
  Tsukamoto, Bioscience, biotechnology, and biochemistry 2024 (PubMed)
  • GeneRIF: HNF4alpha is required for Tkfc promoter activation by ChREBP.
• Sustained alterations in proximal tubule gene expression in primary culture associate with HNF4A loss.
  Telang, Scientific reports 2024
  • GeneRIF: Sustained alterations in proximal tubule gene expression in primary culture associate with HNF4A loss.
• Impaired hepatic glucose metabolism and liver-α-cell axis in mice with liver-specific ablation of the Hepatocyte Nuclear Factor 4α (Hnf4a) gene.
  Thymiakou, Metabolism: clinical and experimental 2023 (PubMed)
  • GeneRIF: Impaired hepatic glucose metabolism and liver-alpha-cell axis in mice with liver-specific ablation of the Hepatocyte Nuclear Factor 4alpha (Hnf4a) gene.
• More

NR4A3_RAT / P51179 Nuclear receptor subfamily 4 group A member 3; Neuron-derived orphan receptor 1/2; Nuclear hormone receptor NOR-1/NOR-2 from Rattus norvegicus (Rat) (see 7 papers)
NP_113816 nuclear receptor subfamily 4 group A member 3 from Rattus norvegicus
61% identity, 12% coverage

• function: Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner (PubMed:7811288). Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (PubMed:10523643). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site (By similarity). Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression (PubMed:16945922). In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A (PubMed:24706823). Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development (By similarity). Also mediates survival of neuron and smooth muscle cells; mediates CREB- induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription (By similarity). Also plays a role in inflammation; Upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site (By similarity). In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation. Also plays a role in metabolism; by modulating feeding behavior; and by playing a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP-glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1. Upon catecholamines stimulation, regulates gene expression that controls oxidative metabolism in skeletal muscle (By similarity). Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface (By similarity). Finally, during gastrulation plays a crucial role in the formation of anterior mesoderm by controlling cell migration (By similarity). Also participates in cardiac hypertrophy by activating PARP1 (PubMed:25625556).
  subunit: Interacts with SIX3 (via homeobox); differentially regulates the transcriptional activities of NR4A3. Interacts with NR3C1 (via nuclear receptor DNA-binding domain); the interactions represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE) (PubMed:15591535). Interacts with TRIM28; the interactions potentiates NR4A3 activity on NurRE promoter (PubMed:19321449). Binds DNA as a monomer and homodimer (PubMed:10523643). Interacts with PARP1; activates PARP1 by improving acetylation of PARP1 and suppressing the interaction between PARP1 and SIRT1 (PubMed:25625556). Interacts with the constituents of DNA-PK heterotrimer PRKDC, XRCC6 and XRCC5; phosphorylates and prevents NR4A3 ubiquitinylation and degradation (By similarity). Interacts with NCOA2; potentiates the activity of the NR4A3. Interacts with NCOA1, NCOA3, MED1 and KAT2B. Interacts with EP300 and NCOA2; mediates the recruitment of MED1 in the coactivator complex (By similarity).
• Oxidative stress-induced EGR1 upregulation promotes NR4A3-mediated nucleus pulposus cells apoptosis in intervertebral disc degeneration.
  Zheng, Aging 2024
  • GeneRIF: Oxidative stress-induced EGR1 upregulation promotes NR4A3-mediated nucleus pulposus cells apoptosis in intervertebral disc degeneration.
• Sequential preovulatory expression of a gonadotropin-releasing hormone-inducible gene, Nr4a3, and its suppressor Anxa5 in the pituitary gland of female rats.
  Terashima, The Journal of reproduction and development 2021
  • GeneRIF: Sequential preovulatory expression of a gonadotropin-releasing hormone-inducible gene, Nr4a3, and its suppressor Anxa5 in the pituitary gland of female rats.
• β-Cell deletion of Nr4a1 and Nr4a3 nuclear receptors impedes mitochondrial respiration and insulin secretion.
  Reynolds, American journal of physiology. Endocrinology and metabolism 2016 (PubMed)
  • GeneRIF: Loss of Nr4a1 and Nr4a3 impedes production of ATP and ultimately inhibits glucose-stimulated insulin secretion. These data demonstrate for the first time that the orphan nuclear receptors Nr4a1 and Nr4a3 are critical for beta-cell mitochondrial function and insulin secretion.
• Regulation of NR4A by nutritional status, gender, postnatal development and hormonal deficiency.
  Pérez-Sieira, Scientific reports 2014
  • GeneRIF: The expression of Nur77, Nurr1 and Nor 1 in the white adipose tissue is regulated by nutritional and hormonal status.
• Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.
  Tessem, Proceedings of the National Academy of Sciences of the United States of America 2014
  • GeneRIF: Nkx6.1 and Nr4a receptors induce components of the anaphase-promoting complex, including ubiquitin-conjugating enzyme E2C, resulting in degradation of the cell cycle inhibitor p21
• Epigenetic regulation of the NR4A orphan nuclear receptor NOR1 by histone acetylation.
  Zhao, FEBS letters 2014
  • GeneRIF: mechanisms of NOR1 regulation
• Over-expression of neuron-derived orphan receptor-1 (NOR-1) exacerbates neointimal hyperplasia after vascular injury.
  Rodríguez-Calvo, Human molecular genetics 2013 (PubMed)
  • GeneRIF: Over-expression of neuron-derived orphan receptor-1 (NOR-1) exacerbates neointimal hyperplasia after vascular injury
• Divergent skeletal muscle respiratory capacities in rats artificially selected for high and low running ability: a role for Nor1?
  Stephenson, Journal of applied physiology (Bethesda, Md. : 1985) 2012
  • GeneRIF: differential expression of Nor1 may contribute to the differences in metabolic regulation between high running capacity (HCR) and low running capacity (LCR) phenotypes
• More

Q4W6C8 Ultraspiracle from Leptinotarsa decemlineata
57% identity, 19% coverage

• The molecular basis of conformational instability of the ecdysone receptor DNA binding domain studied by in silico and in vitro experiments
  Szamborska-Gbur, PloS one 2014
  • “...X receptor alpha (RXR) and human farnesoid X-activated receptor beta (FXR) (UniProt identifiers: Q9NG48, Q5MBF7, Q4W6C8, P19793 and Q96RI1, respectively) (see Figure S1 ). Additionally, the selected amino acid positions (16, 49, 58, 61 and 64) of the EcRDBD sequence were analyzed in D. melanogaster and...”

XP_006256022 retinoic acid receptor RXR-beta isoform X1 from Rattus norvegicus
55% identity, 12% coverage

• Fundamental studies of adrenal retinoid-X-receptor: Protein isoform, tissue expression, subcellular distribution, and ligand availability.
  Cheng, The Journal of steroid biochemistry and molecular biology 2017 (PubMed)
  • GeneRIF: Data suggest cells of the adrenal gland that contain RXRalpha are primarily localized in zona fasciculata and adrenal medulla with RXRalpha almost exclusively localized in cell nucleus; cells that contain RXRbeta are primarily localized in zona fasciculata. RXR ligands, such as all-trans-retinoic acid and long-chain polyunsaturated fatty acids, are also present in the adrenal gland.
• Expression of retinoic acid receptors and retinoid X receptors in normal and vitamin A deficient adult rat brain.
  Arfaoui, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 2013 (PubMed)
  • GeneRIF: RARalpha and beta isotypes were detected in practically all the male rat brain areas whereas immunostaining was weak or absent in the female brain except RARalpha.
• Retinoic acid receptor beta mediates all-trans retinoic acid facilitation of mesenchymal stem cells neuronal differentiation.
  Gong, The international journal of biochemistry & cell biology 2013 (PubMed)
  • GeneRIF: all-trans retinoic acid pre-induction facilitates the neuronal differentiation of mesenchymal stem cells
• Ectopic expression of retinoic acid receptors and change of myocardial structure in the offspring heart with vitamin A deficiency.
  Feng, Journal of nutritional science and vitaminology 2012 (PubMed)
  • GeneRIF: We showed that the embryo hearts from vitamin A insufficient groups exhibited ultrastructural changes and significantly lowe expression of GATA-4, RARalpha and gamma, and higher expression of RXRalpha and beta.
• Sequential RARbeta and alpha signalling in vivo can induce adult forebrain neural progenitor cells to differentiate into neurons through Shh and FGF signalling pathways.
  Goncalves, Developmental biology 2009 (PubMed)
  • GeneRIF: Data describe the role of retinoic acid receptor beta and alpha signalling in adult forebrain neural progenitor cells, and show that RARbeta activation stimulates Sonic hedgehog signalling and induces the cell proliferation.
• Dietary soy protein isolate modifies hepatic retinoic acid receptor-beta proteins and inhibits their DNA binding activity in rats.
  Xiao, The Journal of nutrition 2007 (PubMed)
  • GeneRIF: dietary soy proteins affect hepatic RARbeta2 protein content and RARbeta DNA binding activity.

XP_011259848 nuclear hormone receptor E75 isoform X3 from Camponotus floridanus
62% identity, 8% coverage

• Identification and temporal expression of putative circadian clock transcripts in the amphipod crustacean Talitrus saltator
  O'Grady, PeerJ 2016
  • “...hormone receptor E75, the non-mammalian REVERB homologue in the carpenter ant Camponotus floridanus (Accession No. XP_011259848 ). The closest aligning protein in FlyBase was the Drosophila melanogaster E75 protein ( FBpp0297726 ). Sirt 1, 2, 4, 6 and 7 Five contig sequences of lengths 4,033 bp,...”

HNF4A_XENLA / Q91766 Hepatocyte nuclear factor 4-alpha; HNF-4-alpha; Nuclear receptor subfamily 2 group A member 1 from Xenopus laevis (African clawed frog) (see paper)
54% identity, 16% coverage

• function: Transcriptional regulator; binds and activates the promoter for the HNF1-alpha gene (PubMed:8808405). Potential initiator of a transcriptional cascade within a subset of cells committed to a specific developmental program (PubMed:8808405). Could be a determinant for asymmetry in early development (PubMed:8808405). May play a role in the regulation of the circadian clock (By similarity).
  subunit: Homodimerization is required for HNF4-alpha to bind to its recognition site.

XP_015135069 nuclear receptor subfamily 6 group A member 1 isoform X2 from Gallus gallus
55% identity, 16% coverage

• Molecular cloning and characterization of the germ cell-related nuclear orphan receptor in chickens.
  Lee, Molecular reproduction and development 2010 (PubMed)
  • GeneRIF: The cloned cNR6A1 sequence was mapped to chromosome 17 and contained an open reading frame of 1.4 kb encoding 445 amino acids. Data suggest that cNR6A1 may play an important role during chicken embryonic development and differentiation.

Q3I5Q8 E75 nuclear receptor from Gecarcinus lateralis
62% identity, 9% coverage

• Transcriptome Analysis and Differential Gene Expression on the Testis of Orange Mud Crab, Scylla olivacea, during Sexual Maturation
  Waiho, PloS one 2017
  • “...Bursicon hormone alpha subunit C3S7D8 Callinectes sapidus (Blue crab) 96.88 6e-19 Ref_Crab_Transcript_2620_1085 E75 nuclear receptor Q3I5Q8 Gecarcinus lateralis (Blackback land crab) 95.55 0 Ref_Crab_Transcript_69307_4236 Prohormone convertase D0UJV3 Libinia emarginata (Longnose spider crab) 93.55 2e-9 Ref_Crab_Transcript_15118_512 Pigment dispersing hormone receptor C6L2K2 Penaeus japonicus (Kuruma shrimp) 80.85 1e-16...”

NR4A1_HUMAN / P22736 Nuclear receptor subfamily 4immunitygroup A member 1; Early response protein NAK1; Nuclear hormone receptor NUR/77; Nur77; Orphan nuclear receptor HMR; Orphan nuclear receptor TR3; ST-59; Testicular receptor 3 from Homo sapiens (Human) (see 13 papers)
59% identity, 12% coverage

• function: Orphan nuclear receptor. Binds the NGFI-B response element (NBRE) 5'-AAAGGTCA-3' (PubMed:18690216, PubMed:8121493, PubMed:9315652). Binds 9-cis-retinoic acid outside of its ligand- binding (NR LBD) domain (PubMed:18690216). Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation (PubMed:22983157). Regulates the inflammatory response in macrophages by regulating metabolic adaptations during inflammation, including repressing the transcription of genes involved in the citric acid cycle (TCA) (By similarity). Inhibits NF-kappa-B signaling by binding to low-affinity NF-kappa-B binding sites, such as at the IL2 promoter (PubMed:15466594). May act concomitantly with NR4A2 in regulating the expression of delayed-early genes during liver regeneration (By similarity). Plays a role in the vascular response to injury (By similarity).
  function: In the cytosol, upon its detection of both bacterial lipopolysaccharide (LPS) and NBRE-containing mitochondrial DNA released by GSDMD pores during pyroptosis, it promotes non-canonical NLRP3 inflammasome activation by stimulating association of NLRP3 and NEK7.
  cofactor: Zn(2+) (Binds 2 zinc ions.)
  subunit: Binds the NGFI-B response element (NBRE) as a monomer (PubMed:18690216). Binds the Nur response element (NurRE), consisting of two inverse NBRE-related octanucleotide repeats separated by 6 base- pairs, as a dimer (PubMed:18690216, PubMed:9315652). Interacts (via N- terminus) with NLRP3 (via LRR repeat domain); the interaction is direct, requires binding of NR4A1/Nur77 to NBRE-containing dsDNA and lipopolysaccharide, and leads to non-canonical NLRP3 inflammasome activation (By similarity). Interacts with GADD45GIP1 (PubMed:15459248). Interacts with STK11 (PubMed:22983157). Interacts with IFI27 (PubMed:22427340). Heterodimer (via DNA-binding domain) with RXRA (via C-terminus); DNA-binding of the heterodimer is enhanced by 9- cis retinoic acid (PubMed:15509776, PubMed:17761950). Competes for the RXRA interaction with EP300 and thereby attenuates EP300 mediated acetylation of RXRA (PubMed:17761950). Interacts with NCOA1 (PubMed:18690216). Interacts with NCOA2 (PubMed:18690216). Interacts with NCOA3 (PubMed:18690216).
• Screening COPD-Related Biomarkers and Traditional Chinese Medicine Prediction Based on Bioinformatics and Machine Learning.
  Cao, International journal of chronic obstructive pulmonary disease 2024
  • “...ADIPOQ Q15848 Adiponectin 18 LTA P01374 Lymphotoxin-alpha 19 ACE2 Q9BYF1 Angiotensin-converting enzyme 2 20 NR4A1 P22736 Nuclear receptor subfamily 4immunitygroup A member 1 21 IL10 P22301 Interleukin-10 22 GFAP P14136 Glial fibrillary acidic protein 23 MYC P01106 Myc proto-oncogene protein Table 2 Candidate Compounds and Potential...”
• Tretinoin synergistically enhances the antitumor effect of combined BRAF, MEK, and EGFR inhibition in BRAFV600E colorectal cancer.
  Yoshida, Cancer science 2024
  • “...P51452, Q12852, P35968, Q15303, P23560, P04626, P31749, O95382, P04629, Q02750, P10721, P31751, P15336, P10398, Q00653, P22736, P15056, Q16690, Q04206, P01106, P08069, O95819 PI3KAkt signaling pathway 23 5.75E12 P35968, Q15303, P23560, P31946, P10415, P04626, P31749, P04629, Q02750, P10721, P31751, P15336, P54646, P22736, Q04206, P23588, P24941, P01106, P08069,...”
• Proteomics and Metabolomics Analysis Reveals the Toxicity of ZnO Quantum Dots on Human SMMC-7721 Cells.
  Yang, International journal of nanomedicine 2023
  • “...Down Q5T6F2 Ubiquitin-associated protein 2 UBAP2 Down Q9UK53 Inhibitor of growth protein 1 ING1 Down P22736 Nuclear receptor subfamily 4 group A member 1 NR4A1 Down High Dose vs Control Q9H4H8 Protein FAM83D FA83D Up Q8IXZ2 Zinc finger CCCH domain-containing protein 3 ZC3H3 Up P26447 Protein...”
• Effect of metformin on nonalcoholic fatty liver based on meta-analysis and network pharmacology
  Huang, Medicine 2022
  • “...factor kappa-B kinase 756 PIK3CA P42336 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 1068 NR4A1 P22736 Nuclear receptor subfamily 4 group A member 1 598 DPP9 Q86TI2 Dipeptidyl peptidase 9 863 HIF1A Q16665 Hypoxia-inducible factor 1-alpha 826 NFE2L2 Q16236 Nuclear factor erythroid 2-related factor 2 605...”
• Network pharmacology and molecular docking reveal the effective substances and active mechanisms of Dalbergia Odoriferain protecting against ischemic stroke
  Liu, PloS one 2021
  • “...P09874 Poly [ADP-ribose] polymerase-1 PARP1 39 O14672 ADAM10 ADAM10 40 P25774 Cathepsin S CTSS 41 P22736 Nuclear receptor subfamily 4 group A member 1 NR4A1 42 P42574 Caspase-3 CASP3 43 P60568 Interleukin-2 IL2 44 P24557 Thromboxane-A synthase TBXAS1 45 P27169 Serum paraoxonase/arylesterase 1 PON1 46 Q92934...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2021
  • “...related 1 Neuronderived orphan receptor 1 Systematic nomenclature NR4A1 NR4A2 NR4A3 HGNC, UniProt NR4A1 , P22736 NR4A2 , P43354 NR4A3 , Q92570 Comments An endogenous agonist, cytosporone B , has been described [ 164 ], although structural analysis and molecular modelling has not identified a ligand...”
• [Fuxinfang improves hypoxia-induced injury of human aortic endothelial cells by regulating c-Fos-NR4A1-p38 pathway].
  Xu, Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2021
• The nuclear receptor NR4A1 is regulated by SUMO modification to induce autophagic cell death
  Zárraga-Granados, PloS one 2020
  • “...potential site for SUMOylation in NR4A1 (positions numbers refer to the human canonic sequence UniProtKB P22736) ( Fig 1A ). We confirmed that during SP/NK 1 R-induced cell death autophagy is induced, as we observed autophagosomes by ultrastructure analysis. Endogenous LC3 was localized by immunoelectron microscopy,...”
• More

LOC117872690 nuclear receptor subfamily 4 group A member 3-like from Trachemys scripta elegans
61% identity, 14% coverage

• Comparison of the Single-Cell Immune Landscape of Testudines from Different Habitats
  Guo, Cells 2022
  • “..., LOC117885781 , GATA2 , TNFAIP8L3 , and GPC1 ; GATA2-low-basophils: LOC117886291 , LIF , LOC117872690 , LOC117883374 , and TGFB2 ; C. carbonaria : TGFB2 , LOC116816807 , SLC38A11 , CST7 , and RAB27B ; P. sinensis : LOC102456708 , LOC102455777 , SYTL2 , LOC102454962...”

NP_001189162 nuclear receptor subfamily 4immunitygroup A member 1 isoform 2 from Homo sapiens
59% identity, 12% coverage

• Chemokine receptor CXCR4 interacts with nuclear receptor Nur77 and promote glioma invasion and progression.
  Dai, Brain research 2024 (PubMed)
  • GeneRIF: Chemokine receptor CXCR4 interacts with nuclear receptor Nur77 and promote glioma invasion and progression.
• SOCS3, Transcriptionally Activated by NR4A1, Induces Apoptosis and Extracellular Matrix Degradation of Vaginal Fibroblasts in Pelvic Organ Prolapse
  Jin, Balkan medical journal 2024
  • GeneRIF: SOCS3, Transcriptionally Activated by NR4A1, Induces Apoptosis and Extracellular Matrix Degradation of Vaginal Fibroblasts in Pelvic Organ Prolapse.
• NR4A1 depletion inhibits colorectal cancer progression by promoting necroptosis via the RIG-I-like receptor pathway.
  Zhu, Cancer letters 2024 (PubMed)
  • GeneRIF: NR4A1 depletion inhibits colorectal cancer progression by promoting necroptosis via the RIG-I-like receptor pathway.
• Hyperinsulinemia impairs decidualization via AKT-NR4A1 signaling: new insight into polycystic ovary syndrome (PCOS)-related infertility.
  Jiang, Journal of ovarian research 2024
  • GeneRIF: Hyperinsulinemia impairs decidualization via AKT-NR4A1 signaling: new insight into polycystic ovary syndrome (PCOS)-related infertility.
• Progressive reduction of nuclear receptor Nr4a1 mediates age-dependent cognitive decline.
  Chen, Alzheimer's & dementia : the journal of the Alzheimer's Association 2024
  • GeneRIF: Progressive reduction of nuclear receptor Nr4a1 mediates age-dependent cognitive decline.
• The Long Non-Coding RNA MALAT1 Modulates NR4A1 Expression through a Downstream Regulatory Element in Specific Cancer Cell Types.
  Wernig-Zorc, International journal of molecular sciences 2024
  • GeneRIF: The Long Non-Coding RNA MALAT1 Modulates NR4A1 Expression through a Downstream Regulatory Element in Specific Cancer Cell Types.
• NR4A1 mediates NK-cell dysfunction in hepatocellular carcinoma via the IFN-γ/p-STAT1/IRF1 pathway.
  Yu, Immunology 2023 (PubMed)
  • GeneRIF: NR4A1 mediates NK-cell dysfunction in hepatocellular carcinoma via the IFN-gamma/p-STAT1/IRF1 pathway.
• Silencing lncRNA CDKN2B-AS1 Alleviates Childhood Asthma Progression Through Inhibiting ZFP36 Promoter Methylation and Promoting NR4A1 Expression.
  Chen, Inflammation 2023 (PubMed)
  • GeneRIF: Silencing lncRNA CDKN2B-AS1 Alleviates Childhood Asthma Progression Through Inhibiting ZFP36 Promoter Methylation and Promoting NR4A1 Expression.
• More

XP_005206277 nuclear receptor subfamily 4 group A member 1 isoform X1 from Bos taurus
NP_001069379 nuclear receptor subfamily 4 group A member 1 from Bos taurus
59% identity, 12% coverage

• Fibroblast growth factor-2 regulation of Sprouty and NR4A genes in bovine ovarian granulosa cells.
  Jiang, Journal of cellular physiology 2011 (PubMed)
  • GeneRIF: Identify the orphan nuclear receptor NR4A1 as a potential early response gene in FGF2 signaling and regulation of sprouty in bovine ovarian granulosa cells.
• Schistosoma mansoni: identification of SmNR4A, a member of nuclear receptor subfamily 4
  Wu, Experimental parasitology 2008
  • “...NR38 ( Apis mellifera (honey bee) NR38): XP_623628 ; Cattle NR4A1 ( Bos Taurus NR4A1): NP_001069379 ; Cattle NR4A2 ( Bos Taurus NR4A2): NP_001069676 ; Chicken NR4A3 ( Gallus gallus (red jungle fowl) NR4A3): XP_419081 ; Drosophila HR38 ( D. melanogaster HR38): CAA61534 ; Drosophila FTZ-F1...”

NP_001257860 hepatocyte nuclear factor 4-alpha isoform 2 from Rattus norvegicus
54% identity, 16% coverage

• Mechanism and Effect of HNF4α Decrease in a Rat Model of Cirrhosis and Liver Failure.
  Melis, Cellular and molecular gastroenterology and hepatology 2024
  • GeneRIF: Mechanism and Effect of HNF4alpha Decrease in a Rat Model of Cirrhosis and Liver Failure.
• HNF4A Negatively Regulated Posterior Capsular Opacification via Transcriptional Inhibition of MMP2.
  Hu, Current eye research 2023 (PubMed)
  • GeneRIF: HNF4A Negatively Regulated Posterior Capsular Opacification via Transcriptional Inhibition of MMP2.
• Targeted Activation of HNF4α by AMPK Inhibits Apoptosis and Ameliorates Neurological Injury Caused by Cardiac Arrest in Rats.
  Zhan, Neurochemical research 2023
  • GeneRIF: Targeted Activation of HNF4alpha by AMPK Inhibits Apoptosis and Ameliorates Neurological Injury Caused by Cardiac Arrest in Rats.
• hsa-miR-34a-5p Ameliorates Hepatic Ischemia/Reperfusion Injury Via Targeting HNF4α.
  Zheng, The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 2022
  • GeneRIF: hsa-miR-34a-5p Ameliorates Hepatic Ischemia/Reperfusion Injury Via Targeting HNF4alpha.
• Immunohistochemical detection of hepatocyte nuclear factor-4α in vertebrates.
  Jiang, Microscopy research and technique 2021 (PubMed)
  • GeneRIF: Immunohistochemical detection of hepatocyte nuclear factor-4alpha in vertebrates.
• Molecular and ultrastructure study of endoplasmic reticulum stress in hepatic steatosis: role of hepatocyte nuclear factor 4α and inflammatory mediators.
  Abo, Histochemistry and cell biology 2020 (PubMed)
  • GeneRIF: The endoplasmic reticulum stress, confirmed at ultrastructure level, plays an important role in pathogenesis of HFD-induced hepatic steatosis. HNF4alpha downregulation as well as increased expression of hs-CRP and TNF-alpha enforce the concept of interplay between ER stress, hepatic subclinical inflammation, and disturbed gene expression regulation in the pathogenesis of HFD-induced hepatic steatosis.
• Genetic and Epigenetic Modification of Rat Liver Progenitor Cells via HNF4α Transduction and 5' Azacytidine Treatment: An Integrated miRNA and mRNA Expression Profile Analysis.
  Bolleyn, Genes 2020
  • GeneRIF: Genetic and Epigenetic Modification of Rat Liver Progenitor Cells via HNF4alpha Transduction and 5' Azacytidine Treatment: An Integrated miRNA and mRNA Expression Profile Analysis.
• Maternal Malnutrition Affects Hepatic Metabolism through Decreased Hepatic Taurine Levels and Changes in HNF4A Methylation.
  Du, International journal of molecular sciences 2020
  • GeneRIF: Maternal Malnutrition Affects Hepatic Metabolism through Decreased Hepatic Taurine Levels and Changes in HNF4A Methylation.
• More

LOC100695791 LOW QUALITY PROTEIN: nuclear receptor subfamily 2 group F member 6 from Oreochromis niloticus
61% identity, 18% coverage

• Neurogenomic Profiling Reveals Distinct Gene Expression Profiles Between Brain Parts That Are Consistent in Ophthalmotilapia Cichlids
  Derycke, Frontiers in neuroscience 2018
  • “...as transport, transmembrane transport, transcription (and its regulation) and signal transduction (Table S3 ). Gene LOC100695791 is involved in the steroid hormone mediated signaling pathway. The expression patterns of each of the 32 genes across the brain parts in both species are presented in Figure S4...”

RORG_MOUSE / P51450 Nuclear receptor ROR-gamma; Nuclear receptor RZR-gamma; Nuclear receptor subfamily 1 group F member 3; RAR-related orphan receptor C; Retinoid-related orphan receptor-gamma; Thymus orphan receptor; TOR from Mus musculus (Mouse) (see 20 papers)
63% identity, 14% coverage

• function: Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts (PubMed:17666523, PubMed:19381306, PubMed:19965867, PubMed:21853531, PubMed:22789990, PubMed:23723244). Regulates the circadian expression of clock genes such as CRY1, BMAL1 and NR1D1 in peripheral tissues and in a tissue-selective manner (PubMed:22753030). Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORC-mediated activation of the expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock (PubMed:22753030). Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A. Negative regulator of adipocyte differentiation through the regulation of early phase genes expression, such as MMP3. Controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. In liver, has specific and redundant functions with RORA as positive or negative modulator of expression of genes encoding phase I and Phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as SULT1E1 (PubMed:21853531). Also plays a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC1 and PCK1. Regulates the rhythmic expression of PROX1 and promotes its nuclear localization.
  function: [Isoform 2]: Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyer's patches (PubMed:10602018, PubMed:14691482, PubMed:16148126). Required for the generation of LTi (lymphoid tissue inducer) cells. Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2. Also plays a key role, downstream of IL6 and TGFB and synergistically with RORA, for lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus (PubMed:16990136, PubMed:18164222, PubMed:26607793). May also play a role in the pre-TCR activation cascade leading to the maturation of alpha/beta T-cells and may participate in the regulation of DNA accessibility in the TCR-J(alpha) locus (PubMed:10602018, PubMed:14691482, PubMed:16148126, PubMed:16990136, PubMed:18164222, PubMed:9881970). Plays an indispensable role in the induction of IFN- gamma dependent anti-mycobacterial systemic immunity (By similarity).
  subunit: Interacts (via AF-2 motif) with the coactivators NCOA1, NCOA2 and PPARGC1A (via LXXLL motif) (PubMed:16148126, PubMed:17476214, PubMed:21499262). Interacts with the corepressor NCOR1 (PubMed:21499262). Interacts with CRY1 (PubMed:22170608). Interacts (via AF-2 motif) with PROX1 (PubMed:23723244). Interacts with FOXP3 (PubMed:18368049). Interacts with NR0B2 (PubMed:25212631).
  disruption phenotype: Mice show decreased adipocytes size and highly insulin sensitivity, leading to an improved control of circulating fatty acids. Mutants are protected from hyperglycemia and insulin resistance in the state of obesity. Loss of circadian pattern of some clock genes expression in the peripheral tissues and massive apoptosis of thymocytes. Knockout mice for isoform 2 lack all lymph nodes and Peyer's patches, as well as LTi cells. They also show a reduction of T(H)17 cells in the lamina propria by at least 10-fold to less than 1% of the T(H) cells. Mice are less susceptible to autoimmune inflammatory diseases.
• An integrated approach towards the development of novel antifungal agents containing thiadiazole: synthesis and a combined similarity search, homology modelling, molecular dynamics and molecular docking study
  Er, Chemistry Central journal 2018
  • “...SENP7 (Q9BQF6) Homo sapiens 16.8 488904 878365 CASP3 (P42574) Homo sapiens 18.9 488901 3669135 Rorc (P51450) Mus musculus 17.7828 2551 3669135 SENP7 (Q9BQF6) Homo sapiens Active 434973 3669135 PAFAH1B2 (P68402) Homo sapiens Active 492953 3669135 MC4R (P32245) Homo sapiens Active 540308 753766 FAK1 (Q05397) Homo sapiens...”
• Orthologue chemical space and its influence on target prediction
  Mervin, Bioinformatics (Oxford, England) 2018
  • “...dominated by Nuclear receptor ROR-gamma receptors (RORC), due to a human-orthologue pair between P51449 and P51450, with data from two PubChem qHTS assays (CHEMBL1614441 and CHEMBL1614087) comprising 11781 and 7452 actives, respectively. For contrast, a ROR training set comprising only human data would only include 418...”

XP_011237327 nuclear receptor subfamily 6 group A member 1 isoform X1 from Mus musculus
55% identity, 15% coverage

• Hippocampal NR6A1 impairs CREB-BDNF signaling and leads to the development of depression-like behaviors in mice.
  Tan, Neuropharmacology 2022 (PubMed)
  • GeneRIF: Hippocampal NR6A1 impairs CREB-BDNF signaling and leads to the development of depression-like behaviors in mice.
• A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF), and Liver Receptor Homolog-1 (LRH-1).
  Weikum, Journal of molecular biology 2016
  • GeneRIF: Here, the authors present the first structure of mouse GCNF DNA-binding domain in complex with the Oct4 DR0. The overall structure revealed two molecules bound in a head-to-tail fashion on opposite sides of the DNA at a DR0 motif located within the Oct4 promoter.
• GCNF-dependent activation of cyclin D1 expression via repression of Mir302a during ESC differentiation.
  Wang, Stem cells (Dayton, Ohio) 2014
  • GeneRIF: These results reveal that GCNF plays a key role in regulating activation of cyclin D1 expression via inhibition of Mir302a.
• Germ cell nuclear factor regulates gametogenesis in developing gonads.
  Sabour, PloS one 2014
  • GeneRIF: Inactivation of the Gcnf gene in vivo leads to loss of repression of Oct4 expression in both male and female gonads.
• Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts.
  Gurtan, Genes & development 2013
  • GeneRIF: characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss
• The ligand binding domain of GCNF is not required for repression of pluripotency genes in mouse fetal ovarian germ cells.
  Okumura, PloS one 2013
  • GeneRIF: Gcnf is expressed in fetal ovarian germ cells.
• Differential recruitment of methyl CpG-binding domain factors and DNA methyltransferases by the orphan receptor germ cell nuclear factor initiates the repression and silencing of Oct4.
  Gu, Stem cells (Dayton, Ohio) 2011
  • GeneRIF: GCNF initiates the repression and epigenetic modification of Oct4 gene during ESC differentiation.
• Transcriptional regulation of the hypocretin/orexin gene by NR6A1.
  Tanaka, Biochemical and biophysical research communications 2010
  • GeneRIF: These experiments confirmed that NR6A1 works as a regulator for hypocretin transcription.
• More

NR6A1_MOUSE / Q64249 Nuclear receptor subfamily 6 group A member 1; Germ cell nuclear factor; GCNF; mGCNF; Retinoid receptor-related testis-specific receptor; RTR from Mus musculus (Mouse) (see 6 papers)
55% identity, 15% coverage

• function: Orphan nuclear receptor that binds to a response element containing the sequence 5'-TCAAGGTCA-3' (PubMed:11702949, PubMed:27984042, PubMed:7854358). Acts as a regulator of embryonic stem cell pluripotency by mediating repression of POU5F1/OCT4: binds to the DR0 element within the POU5F1/OCT4 promoter and inhibits POU5F1/OCT4 expression during embryonic stem cell differentiation (PubMed:11702949, PubMed:27984042). Required to restrict POU5F1/OCT4 expression to the germ cell lineage (PubMed:11702949). Involved in the regulation of gene expression in germ cell development during gametogenesis (PubMed:7854358).
  subunit: Homodimer (PubMed:27984042). Interacts with UIMC1 (PubMed:12080054, PubMed:7760852).
• A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF), and Liver Receptor Homolog-1 (LRH-1).
  Weikum, Journal of molecular biology 2016
  • “...Protein expression and purification The DNA binding domain (DBD) of mouse GCNF (residues 69180, UniProt Q64249) with a C104S mutation was cloned into a pMCGS7 vector with a 6X-Histidine tag. GCNF was expressed in BL21 (DE3) pLysS E. coli cells. The protein was grown at 37...”

FTZF1_DROME / P33244 Nuclear hormone receptor FTZ-F1; FTZ-F1 alpha; Nuclear receptor subfamily 5 group A member 3 from Drosophila melanogaster (Fruit fly) (see 5 papers)
59% identity, 7% coverage

• function: Acts as a cofactor to fushi tarazu (ftz) (PubMed:9020363, PubMed:9020364). Facilitates the binding of ftz to DNA (PubMed:9020363, PubMed:9020364). Binds the sequence element 5'-YCYYGGYCR-3' in the zebra element of ftz (PubMed:9020363, PubMed:9020364). Probably functions as a nuclear receptor for a yet unknown ligand (PubMed:23737522, PubMed:9020363, PubMed:9020364). In contrast to vertebrate homologs, not activated by phospholipids (PubMed:23737522).
  subunit: Monomer; forms a complex with ftz.
  disruption phenotype: Ftz-like pair-rule cuticular defects.
• Interaction patterns of methoprene-tolerant and germ cell-expressed Drosophila JH receptors suggest significant differences in their functioning
  Kolonko-Adamska, Frontiers in molecular biosciences 2023
  • “...(661959 aa) was cloned into the pET-M11 vector. Next, the cDNA encoding the Ftz-F1 LDB (P33244, 7861027 aa) was synthesized (Gene Art Thermo Fisher Scientific) and cloned into the pET-15b vector. Both vectors introduced a 6 His tag at the protein N-terminus. GceC and Ftz-F1 LBD...”
• Origins and evolutionary diversification of the nuclear receptor superfamily
  Owen, Cellular and molecular life sciences : CMLS 2000
  • “...from the Cnidaria jellyfish, FTZ-F1 (accession number P33244) which is from Drosophila, NHR-6 (CNR-8/ceb-1 accession number AAD03682), NHR-18 (accession number...”
• Trinucleotide repeats and long homopeptides in genes and proteins associated with nervous system disease and development
  Karlin, Proceedings of the National Academy of Sciences of the United States of America 1996
  • “...A5, Q8, Q13, All, Q1s, A1l, (P25822) Q6, Alo, A6 Ftz-F1 (P33244) 1043 Q0, A6, Ts, N7, N7, T5, Q7, G9, Gs, DSX, male (P23023) ELAV (P16914) Deformed (P07548) DGK...”

XP_008191375 nuclear hormone receptor FTZ-F1 isoform X4 from Tribolium castaneum
59% identity, 13% coverage

• Role of nuclear receptors NlHR3 and NlFTZ-F1 in regulating molting and reproduction in Nilaparvata lugens (stål)
  Li, Frontiers in physiology 2023
  • “...Tribolium castaneum , XP_008191373), TcFTZ-F1X2 ( Tribolium castaneum , XP_008191374), TcFTZ-F1X3 ( Tribolium castaneum , XP_008191375), ApFTZ-F1X1 ( Acyrthosiphon pisum , XP_008183294), ApFTZ-F1X2 ( Acyrthosiphon pisum , XP_008183295), BgFTZ-F1 ( Blattella germanica , CAQ57670), AaFTZ-F1a ( Aedes aegypti , XP_001654601), AaFTZ-F1b ( Aedes aegypti , CAO79104),...”

RXRB_MOUSE / P28704 Retinoic acid receptor RXR-beta; MHC class I regulatory element-binding protein H-2RIIBP; Nuclear receptor subfamily 2 group B member 2; Retinoid X receptor beta from Mus musculus (Mouse) (see 4 papers)
55% identity, 14% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE).
  subunit: Homodimer (in vitro). Heterodimer with other retinoic acid receptor family members. Binds DNA preferentially as a RAR/RXR heterodimer. Interacts with NR1H3 (By similarity). Interacts with AKAP13 (PubMed:20139090).

RORB_MOUSE / Q8R1B8 Nuclear receptor ROR-beta; Nuclear receptor RZR-beta; Nuclear receptor subfamily 1 group F member 2; Retinoid-related orphan receptor-beta from Mus musculus (Mouse) (see 7 papers)
63% identity, 16% coverage

• function: Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated pathway. In cone photoreceptor cells, regulates transcription of OPN1SW. Involved in the regulation of the period length and stability of the circadian rhythm. May control cytoarchitectural patterning of neocortical neurons during development. May act in a dose-dependent manner to regulate barrel formation upon innervation of layer IV neurons by thalamocortical axons. May play a role in the suppression of osteoblastic differentiation through the inhibition of RUNX2 transcriptional activity.
  function: Isoform 1 is critical for hindlimb motor control and for the differentiation of amacrine and horizontal cells in the retina. Regulates the expression of PTF1A synergistically with FOXN4.
  subunit: Monomer. Interacts with CRX.
  disruption phenotype: Mice are blind, show juvenile ataxia, duck gait, hind paw clasping reflex as well as delayed onset of male fertility. They suffer a degeneration of the retina during postnatal development with severe defects in photoreceptor cell morphology. Mice display reduced anxiety and learned helplessness-related behaviors. They also show a significant increase of the circadian period. Knockouts for isoform 1 display duck gait and lack amacrine and horizontal cells with an excess of ganglion cells in the retina (PubMed:23652001).

XP_006711547 nuclear receptor ROR-gamma isoform X2 from Homo sapiens
62% identity, 13% coverage

• Downregulation of Mirlet7 miRNA family promotes Tc17 differentiation and emphysema via de-repression of RORγt.
  Erice, eLife 2024
  • GeneRIF: Downregulation of Mirlet7 miRNA family promotes Tc17 differentiation and emphysema via de-repression of RORgammat.
• Possible Role of the RORC Gene in Primary and Secondary Lymphedema: Review of the Literature and Genetic Study of Two Rare Causative Variants.
  Michelini, Lymphatic research and biology 2021 (PubMed)
  • GeneRIF: Possible Role of the RORC Gene in Primary and Secondary Lymphedema: Review of the Literature and Genetic Study of Two Rare Causative Variants.
• The expression analyses of RMRP, DDX5, and RORC in RRMS patients treated with different drugs versus naïve patients and healthy controls.
  Rahmani, Gene 2021 (PubMed)
  • GeneRIF: The expression analyses of RMRP, DDX5, and RORC in RRMS patients treated with different drugs versus naive patients and healthy controls.
• Correlations of Helicobacter pylori with liver function, inflammatory factors and serum levels of FoxP3 and RORγt in patients with hepatitis B cirrhosis.
  Zhao, European review for medical and pharmacological sciences 2021 (PubMed)
  • GeneRIF: Correlations of Helicobacter pylori with liver function, inflammatory factors and serum levels of FoxP3 and RORgammat in patients with hepatitis B cirrhosis.
• Cooperativity between the orthosteric and allosteric ligand binding sites of RORγt.
  de, Proceedings of the National Academy of Sciences of the United States of America 2021
  • GeneRIF: Cooperativity between the orthosteric and allosteric ligand binding sites of RORgammat.
• Increased Expression of IL-17A and IL-17F Is Correlated With RUNX1 and RORγT in Pediatric Patients With Primary Immune Thrombocytopenia.
  Elnaenaey, Journal of pediatric hematology/oncology 2021 (PubMed)
  • GeneRIF: Increased Expression of IL-17A and IL-17F Is Correlated With RUNX1 and RORgammaT in Pediatric Patients With Primary Immune Thrombocytopenia.
• Associations of TNFA, IL17A, and RORC mRNA expression levels in peripheral blood leukocytes with obesity-related asthma in adolescents.
  Leija-Martínez, Clinical immunology (Orlando, Fla.) 2021 (PubMed)
  • GeneRIF: Associations of TNFA, IL17A, and RORC mRNA expression levels in peripheral blood leukocytes with obesity-related asthma in adolescents.
• Inherited PD-1 deficiency underlies tuberculosis and autoimmunity in a child.
  Ogishi, Nature medicine 2021
  • GeneRIF: Inherited PD-1 deficiency underlies tuberculosis and autoimmunity in a child.
• More

RORB_HUMAN / Q92753 Nuclear receptor ROR-beta; Nuclear receptor RZR-beta; Nuclear receptor subfamily 1 group F member 2; Retinoid-related orphan receptor-beta from Homo sapiens (Human) (see paper)
63% identity, 16% coverage

• function: Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated pathway. In cone photoreceptor cells, regulates transcription of OPN1SW. Involved in the regulation of the period length and stability of the circadian rhythm. May control cytoarchitectural patterning of neocortical neurons during development. May act in a dose-dependent manner to regulate barrel formation upon innervation of layer IV neurons by thalamocortical axons. May play a role in the suppression of osteoblastic differentiation through the inhibition of RUNX2 transcriptional activity (By similarity).
  function: Isoform 1 is critical for hindlimb motor control and for the differentiation of amacrine and horizontal cells in the retina. Regulates the expression of PTF1A synergistically with FOXN4 (By similarity).
  subunit: Monomer. Interacts with CRX.
• THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2021
  • “...RARrelated orphan receptor Systematic nomenclature NR1F1 NR1F2 NR1F3 HGNC, UniProt RORA , P35398 RORB , Q92753 RORC , P51449 Endogenous agonists cholesterol [ 65 , 112 ] Selective agonists 7hydroxycholesterol [ 14 ], cholesterol sulphate [ 14 , 65 ] Comments The immune system function of...”
• Oxonium Ion Guided Analysis of Quantitative Proteomics Data Reveals Site-Specific O-Glycosylation of Anterior Gradient Protein 2 (AGR2).
  Pirro, International journal of molecular sciences 2021
  • “...Q8NBJ4 Golgi membrane protein 1 LQAAGLPHTEVPQGK H 1 N 1 S 2 619 0.44 GalNAc Q92753 Nuclear receptor ROR-beta QQQSGEAEALAR H 1 N 1 S 2 273 0.68 GlcNAc P14314 Glucosidase 2 subunit beta SEALPTDLPAPSAPDLTEPK H 1 N 1 S 2 775 0.68 GalNAc P30533 Alpha-2-macroglobulin...”
• High-throughput screening identifies FAU protein as a regulator of mutant cystic fibrosis transmembrane conductance regulator channel.
  Tomati, The Journal of biological chemistry 2018
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2017
  • “...RARrelated orphan receptor Systematic nomenclature NR1F1 NR1F2 NR1F3 HGNC, UniProt RORA , P35398 RORB , Q92753 RORC , P51449 Endogenous agonists cholesterol [ 66 , 114 ] Selective agonists 7hydroxycholesterol [ 14 ], cholesterol sulphate [ 14 , 66 ] Comments tretinoin shows selectivity for ROR...”
• Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy.
  Rudolf, European journal of human genetics : EJHG 2016
• The Concise Guide to PHARMACOLOGY 2015/16: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2015
  • “...RARrelated orphan receptor Systematic nomenclature NR1F1 NR1F2 NR1F3 HGNC, UniProt RORA , P35398 RORB , Q92753 RORC , P51449 Endogenous agonists cholesterol (Selective) [ 67 , 115 ] Selective agonists 7hydroxycholesterol [ 15 ], cholesterol sulphate [ 15 , 67 ] Comments tretinoin shows selectivity for...”
• The Concise Guide to PHARMACOLOGY 2013/14: nuclear hormone receptors
  Alexander, British journal of pharmacology 2013
  • “...orphan receptor- RAR-related orphan receptor- Systematic nomenclature NR1F1 NR1F2 NR1F3 HGNC, UniProt RORA, P35398 RORB, Q92753 RORC, P51449 Endogenous agonists (p K i ) cholesterol (Selective) 53 , 54 Selective agonists (p K i ) 7-hydroxycholesterol 51 , cholesterol sulphate 51 , 53 Comments all-trans-retinoic acid...”

XP_017446802 nuclear receptor ROR-gamma isoform X1 from Rattus norvegicus
63% identity, 15% coverage

• [Effect of different orthodontic forces on the expression of T helper cell 17 cell-related cytokines in the pressure side of periodontal tissue in rats].
  Wang, Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology 2021
  • GeneRIF: [Effect of different orthodontic forces on the expression of T helper cell 17 cell-related cytokines in the pressure side of periodontal tissue in rats].
• Mutation of RORγT reveals a role for Th17 cells in both injury and recovery from renal ischemia-reperfusion injury.
  Mehrotra, American journal of physiology. Renal physiology 2020
  • GeneRIF: Mutation of RORgammaT reveals a role for Th17 cells in both injury and recovery from renal ischemia-reperfusion injury.
• An Integrated Analysis of Solid Form Change Impact on Solubility and Permeability: Case Study of Oral Exposure in Rats of an RAR Related Orphan Receptor C Inhibitor.
  Chiang, Journal of pharmaceutical sciences 2019 (PubMed)
  • GeneRIF: Oral Exposure in Rats of an RAR Related Orphan Receptor C Inhibitor.
• Abnormal CD161+ immune cells and retinoic acid receptor-related orphan receptor γt-mediate enhanced IL-17F expression in the setting of genetic hypertension.
  Singh, The Journal of allergy and clinical immunology 2017
  • GeneRIF: Increased RORgammat and IL-17F levels contribute to Spontaneously Hypertensive Rat hypertension and might be therapeutic targets
• Inhibition of the Nuclear Receptor RORγ and Interleukin-17A Suppresses Neovascular Retinopathy: Involvement of Immunocompetent Microglia.
  Talia, Arteriosclerosis, thrombosis, and vascular biology 2016 (PubMed)
  • GeneRIF: RORgamma/IL-17A axis influences VEGF production and neovascular retinopathy by mechanisms involving neuroglia. Inhibition of RORgamma and IL-17A may have potential for the improved treatment of neovascular retinopathies.
• Integrative Genomics Outlines a Biphasic Glucose Response and a ChREBP-RORγ Axis Regulating Proliferation in β Cells.
  Schmidt, Cell reports 2016 (PubMed)
  • GeneRIF: Integrative genomics outlines a biphasic glucose response and a ChREBP-RORgamma axis regulating proliferation in pancreatic beta cells.

XP_020922686 nuclear receptor subfamily 1 group D member 1 isoform X2 from Sus scrofa
62% identity, 12% coverage

• NR1D1 targeting CYP19A1 inhibits estrogen synthesis in ovarian granulosa cells.
  Wang, Theriogenology 2022 (PubMed)
  • GeneRIF: NR1D1 targeting CYP19A1 inhibits estrogen synthesis in ovarian granulosa cells.

RORB_RAT / P45446 Nuclear receptor ROR-beta; Nuclear receptor RZR-beta; Nuclear receptor subfamily 1 group F member 2; Retinoid-related orphan receptor-beta from Rattus norvegicus (Rat) (see 5 papers)
63% identity, 16% coverage

• function: Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated pathway. In cone photoreceptor cells, regulates transcription of OPN1SW. Involved in the regulation of the period length and stability of the circadian rhythm. May control cytoarchitectural patterning of neocortical neurons during development. May act in a dose-dependent manner to regulate barrel formation upon innervation of layer IV neurons by thalamocortical axons. May play a role in the suppression of osteoblastic differentiation through the inhibition of RUNX2 transcriptional activity.
  function: [Isoform 1]: Critical for hindlimb motor control and for the differentiation of amacrine and horizontal cells in the retina. Regulates the expression of PTF1A synergistically with FOXN4 (By similarity).
  subunit: Monomer. Interacts with CRX.

NP_001036819 nuclear receptor ROR-beta isoform 1 from Mus musculus
63% identity, 16% coverage

• An allelic series of spontaneous Rorb mutant mice exhibit a gait phenotype, changes in retina morphology and behavior, and gene expression signatures associated with the unfolded protein response.
  Murray, G3 (Bethesda, Md.) 2023
  • GeneRIF: An allelic series of spontaneous Rorb mutant mice exhibit a gait phenotype, changes in retina morphology and behavior, and gene expression signatures associated with the unfolded protein response.
• Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity.
  Clark, eLife 2020
  • GeneRIF: Cortical RORbeta is required for layer 4 transcriptional identity and barrel integrity.
• miR-219a-5p Regulates Rorβ During Osteoblast Differentiation and in Age-related Bone Loss.
  Aquino-Martinez, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2019
  • GeneRIF: findings demonstrate that miR-219a-5p is involved in the regulation of Rorbeta in both mouse and human bone.
• Rorβ regulates selective axon-target innervation in the mammalian midbrain.
  Byun, Development (Cambridge, England) 2019
  • GeneRIF: Rorbeta is a key developmental mediator of colliculo-thalamic innervation. Such regulation could represent a general mechanism orchestrating long-range neuronal connections in the mammalian brain.
• Osteoprotection Through the Deletion of the Transcription Factor Rorβ in Mice.
  Farr, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2018
  • GeneRIF: These data demonstrate that loss of Rorbeta has beneficial skeletal effects by increasing bone formation and decreasing bone resorption, at least in part through beta-catenin-dependent activation of the Wnt pathway. Thus, inhibition of Rorbeta represents a novel approach to potentially prevent or reverse osteoporosis.
• RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait.
  Koch, Neuron 2017
  • GeneRIF: The inhibitory Pax2+ RORbeta interneuron have a dedicated and specific role in modulating sensory input to the spinal motor system during locomotion and that this inhibition is necessary for fluid stepping movements.
• Mutually repressive interaction between Brn1/2 and Rorb contributes to the establishment of neocortical layer 2/3 and layer 4.
  Oishi, Proceedings of the National Academy of Sciences of the United States of America 2016
  • GeneRIF: results suggest that a mutually repressive mechanism exists between Brn1/2 and Rorb expression and that the established expression of Brn1/2 and Rorb further specifies those neurons into L2/3 and L4, respectively, during UCP maturation
• Feedback induction of a photoreceptor-specific isoform of retinoid-related orphan nuclear receptor β by the rod transcription factor NRL.
  Fu, The Journal of biological chemistry 2014
  • GeneRIF: Data indicate that positive feedback between neural retina leucine zipper factor (NRL) and retinoid-related orphan receptor beta gene (Rorb) genes reinforces the commitment to a rod differentiation fate.
• More

NP_001257887 nuclear receptor ROR-beta from Rattus norvegicus
63% identity, 16% coverage

• Analysis of area-specific expression patterns of RORbeta, ER81 and Nurr1 mRNAs in rat neocortex by double in situ hybridization and cortical box method.
  Hirokawa, PloS one 2008
  • GeneRIF: RORbeta, ER81 and Nurr1 are expressed in rat neocortex

NP_008845 nuclear receptor ROR-beta isoform 1 from Homo sapiens
63% identity, 16% coverage

• Comprehensive analysis of the prognosis and biological significance of RORβ in head and neck squamous cell carcinoma.
  Zheng, Environmental toxicology 2024 (PubMed)
  • GeneRIF: Comprehensive analysis of the prognosis and biological significance of RORbeta in head and neck squamous cell carcinoma.
• RORB, an Alzheimer's disease susceptibility gene, is associated with viral encephalitis, an Alzheimer's disease risk factor.
  Lehrer, Clinical neurology and neurosurgery 2023
  • GeneRIF: RORB, an Alzheimer's disease susceptibility gene, is associated with viral encephalitis, an Alzheimer's disease risk factor.
• RORβ suppresses the stemness of gastric cancer cells by downregulating the activity of the Wnt signaling pathway.
  Wen, Oncology reports 2021
  • GeneRIF: RORbeta suppresses the stemness of gastric cancer cells by downregulating the activity of the Wnt signaling pathway.
• Inherited RORB pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy.
  Sadleir, Epilepsia 2020
  • GeneRIF: Inherited RORB pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy.
• Up-regulated NRIP2 in colorectal cancer initiating cells modulates the Wnt pathway by targeting RORβ.
  Wen, Molecular cancer 2017
  • GeneRIF: Results show that NRIP2 regulates the activity of the Wnt pathway via RORbeta. RORbeta inhibits tumorigenesis and the self-renewal of cancer initiating cells (CCICs) and targets HBP1 in regulating Wnt pathway to inhibit tumorigenesis and the self-renewal of CCICs.
• Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy.
  Rudolf, European journal of human genetics : EJHG 2016
  • GeneRIF: Nonsense variant in RORB was identified in four family members with epilepsy. Two de novo RORB deletions identified in patients with behavioral and cognitive impairment and epilepsy.
• Investigation of associations between NR1D1, RORA and RORB genes and bipolar disorder.
  Lai, PloS one 2015
  • GeneRIF: associations between NR1D1, RORA and RORB genes and bipolar disorder.(
• Retinoic acid-related orphan receptor RORβ, circadian rhythm abnormalities and tumorigenesis (Review).
  Feng, International journal of molecular medicine 2015 (PubMed)
  • GeneRIF: Retinoic acid-related orphan receptor RORbeta, circadian rhythm abnormalities and tumorigenesis
• More

NP_001192143 retinoic acid receptor RXR-beta isoform 1 from Mus musculus
Q3TWJ1 Retinoid X receptor beta from Mus musculus
55% identity, 14% coverage

• Overexpression of retinoid X receptor beta provides protection against oxidized low-density lipoprotein-induced inflammation via regulating PGC1α-dependent mitochondrial homeostasis in endothelial cells.
  Zeng, Biochemical pharmacology 2021 (PubMed)
  • GeneRIF: Overexpression of retinoid X receptor beta provides protection against oxidized low-density lipoprotein-induced inflammation via regulating PGC1alpha-dependent mitochondrial homeostasis in endothelial cells.
• Tumor-specific macrophage targeting through recognition of retinoid X receptor beta.
  Tang, Journal of controlled release : official journal of the Controlled Release Society 2019
  • GeneRIF: Tumor-specific macrophage targeting through recognition of retinoid X receptor beta.
• Role of RXRβ in platelet function and arterial thrombosis.
  Lüsebrink, Journal of thrombosis and haemostasis : JTH 2019 (PubMed)
  • GeneRIF: Role of RXRbeta in platelet function and arterial thrombosis.
• RXR heterodimers orchestrate transcriptional control of neurogenesis and cell fate specification.
  Simandi, Molecular and cellular endocrinology 2018 (PubMed)
  • GeneRIF: the RAR:RXR and LXR:RXR-mediated transcriptional program in embryonic stem cells, neural progenitors and terminally differentiated neurons, is reported.
• Retinoid-X-receptors (α/β) in melanocytes modulate innate immune responses and differentially regulate cell survival following UV irradiation.
  Coleman, PLoS genetics 2014
  • GeneRIF: RXRs modulate post-UVR survival of dermal fibroblasts in a "non-cell autonomous" manner, underscoring their role in immune surveillance, while independently mediating post-UVR melanocyte survival in a "cell autonomous" manner
• Retinoic X receptor subtypes exert differential effects on the regulation of Trh transcription.
  Decherf, Molecular and cellular endocrinology 2013 (PubMed)
  • GeneRIF: RXRA and RXRB display specific roles in modulating T3-dependent regulation of thyrotropin releasing hormone.
• Retinoid receptors trigger neuritogenesis in retinal degenerations.
  Lin, FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2012
  • GeneRIF: Using the light-induced retinal degeneration (LIRD) mouse model, which provides a unique platform for exploring the mechanisms underlying neuritogenesis, we found that retinoid X receptors (RXRs) control neuritogenesis.
• Expression of retinoid X receptor β is induced in astrocytes during corpus callosum demyelination.
  König, Journal of chemical neuroanatomy 2012 (PubMed)
  • GeneRIF: During corpus callosum demyelination, retinoid X receptor beta expression is significantly increased.
• More
• The biochemical effects of carotenoids in orange carrots on the colonic proteome in a mouse model of diet-induced obesity
  Balbuena, Frontiers in nutrition 2024
  • “...ALDH1A3 Q3UIA4 33.6 38.8 46.6 39.4 1.16 1.20 1.02 0.85 Retinoid X receptor beta RXRB Q3TWJ1 361.6 359.4 375.1 358.0 0.99 1.04 1.00 0.95 Retinol dehydrogenase 14 (All-trans and 9-cis) RDH14 Q569U9 1170.1 1207.7 1200.5 1241.9 1.03 0.99 1.03 1.03 Retinol dehydrogenase 16 RDH16 O54909 291.1...”

Q98934 Nuclear orphan receptor ROR-beta from Gallus gallus
63% identity, 16% coverage

• Transcriptome Analysis of Ovarian Follicles Reveals Potential Pivotal Genes Associated With Increased and Decreased Rates of Chicken Egg Production.
  Chen, Frontiers in genetics 2021
  • “...of Rac signal transduction gga04131 O93388 PF 00836 ENOG410IEAZ RORB Down Up Circadian rhythm gga04710 Q98934 PF00104 KOG4216 LWF&LYF PIK3R1 Up Up PI3K-Akt signaling pathway gga427171 A0A1D5PUK7 PF16454 PERP1 Up Up p53 signaling pathway gga421683 R4GHP1 PF00822 KOG4671 ACSBG1 Up Up Fatty acid biosynthesis gga00061 F1NLD6...”

NR6A1_PIG / A0P8Z4 Nuclear receptor subfamily 6 group A member 1; Germ cell nuclear factor; GCNF from Sus scrofa (Pig) (see paper)
55% identity, 15% coverage

• function: Orphan nuclear receptor that binds to a response element containing the sequence 5'-TCAAGGTCA-3'. Acts as a regulator of embryonic stem cell pluripotency by mediating repression of POU5F1/OCT4: binds to the DR0 element within the POU5F1/OCT4 promoter and inhibits POU5F1/OCT4 expression during embryonic stem cell differentiation. Involved in the regulation of gene expression in germ cell development during gametogenesis.
  subunit: Homodimer. Interacts with UIMC1.

NP_001090968 nuclear receptor subfamily 6 group A member 1 from Sus scrofa
55% identity, 15% coverage

• The selected genes NR6A1, RSAD2-CMPK2, and COL3A1 contribute to body size variation in Meishan pigs through different patterns.
  Liu, Journal of animal science 2023
  • GeneRIF: The selected genes NR6A1, RSAD2-CMPK2, and COL3A1 contribute to body size variation in Meishan pigs through different patterns.
• Signatures of de-domestication in autochthonous pig breeds and of domestication in wild boar populations from MC1R and NR6A1 allele distribution.
  Ribani, Animal genetics 2019 (PubMed)
  • GeneRIF: Domestic and wild-type alleles at the MC1R and the NR6A1 genes were present in both domestic and wild populations. Findings of the distribution of MC1R alleles might be useful for tracing back the complex genetic history of autochthonous breeds.
• Association of polymorphisms in NR6A1, PLAG1 and VRTN with the number of vertebrae in Chinese Tongcheng × Large White crossbred pigs.
  Zhang, Animal genetics 2018 (PubMed)
  • GeneRIF: NR6A1, PLAG1 and VRTN are significantly associated with the number of vertebrae in Chinese Tongcheng x Large White crossbred pigs
• Differentiation of meat from European wild boars and domestic pigs using polymorphisms in the MC1R and NR6A1 genes.
  Fontanesi, Meat science 2014 (PubMed)
  • GeneRIF: Recent studies suggest that a missense substitution (p.Pro192Leu) in the nuclear receptor subfamily 6, group A, member 1 (NR6A1) gene, mapped on porcine chromosome 1, is the causative mutation of a QTL affecting the number of vertebrae in pigs.
• Genetic evidence for the introgression of Western NR6A1 haplotype into Chinese Licha breed associated with increased vertebral number.
  Yang, Animal genetics 2009 (PubMed)
  • GeneRIF: this study supports the assumption that the Western NR6A1 haplotypes were introduced into Licha Black and possibly Laiwu and are associated with increased vertebral number

NHR41_CAEEL / Q9N4B8 Nuclear hormone receptor family member nhr-41 from Caenorhabditis elegans (see paper)
NP_500073 Nuclear Hormone Receptor family from Caenorhabditis elegans
60% identity, 12% coverage

• function: Orphan nuclear receptor that may have a role in dauer formation.
• The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: implications for developing new model organisms
  Kaur, PloS one 2015
  • “...AAF45707 BgRXR 3695 LgRXR 206562 RXR AAI10999 RXR2 AAD33428 RXR AAC18599 RXR AAA80681 2C/D HR41 NP_500073 TR AAV80236 HR78 Q24142 BgTR 2718 LgTR * 231979 TR2 AAA36761 TR4 NP_003289 2E FAX AAD55066 TLL * AAW88549 TLL AAB71371 BgTLX * 3 LgTLX 130367 TLX AAL05871 HR67 CAA97428...”

RXRB_HUMAN / P28702 Retinoic acid receptor RXR-beta; Nuclear receptor subfamily 2 group B member 2; Retinoid X receptor beta from Homo sapiens (Human) (see 6 papers)
55% identity, 14% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE).
  subunit: Homodimer (in vitro) (PubMed:11782480). Heterodimer with other retinoic acid receptor family members. Binds DNA preferentially as a RAR/RXR heterodimer (PubMed:1310259). Interacts with NR1H3 (PubMed:12970175). Interacts with AKAP13 (By similarity).
• Retinoid X receptor heterodimers in hepatic function: structural insights and therapeutic potential
  Xu, Frontiers in pharmacology 2024
  • “...genes and receptor degradation ( Giann et al., 2003 ). 2.2 RXR RXR (UniProt ID: P28702) is encoded by a gene located on chromosome 6p21.32 in humans. The RXR protein contains 533 amino acids with a molecular weight of approximately 57kDa. The RXR can form homodimers...”
• FMCA-DTI: a fragment-oriented method based on a multihead cross attention mechanism to improve drug-target interaction prediction.
  Zhang, Bioinformatics (Oxford, England) 2024
  • “...P04798 True True P08684 True True P24462 True True P33260 True True P10632 True True P28702 True True Accuracy 90% Second, we randomly selected two proteins (UGT2B7 and MAOA), chose the drugs that interact with them for testing, and analyzed the accuracy of the prediction. The...”
• Proteomic analysis reveals changes in the proteome of human THP-1 macrophages infected with Paracoccidioides brasiliensis
  de, Frontiers in cellular and infection microbiology 2023
  • “...4042.46 * Q96E17 Ras-related protein Rab-3C 1115.57 * P19793 Retinoic acid receptor RXR-alpha 654.98 * P28702 Retinoic acid receptor RXR-beta 1177.33 * P48443 Retinoic acid receptor RXR-gamma 630.23 * H0Y858 Toll-like receptor 9 (Fragment) 624.89 * A0A499FJK2 Transforming growth factor beta 618.77 * 1 Accession number...”
• Network pharmacology and molecular docking analysis on the mechanism of Baihe Zhimu decoction in the treatment of postpartum depression
  Zhao, Medicine 2022
  • “...P31645 237 CHEK1 O14757 328 DPP4 P27487 56 SLC6A3 Q01959 147 DPP4 P27487 238 RXRB P28702 329 MAPK14 Q16539 57 NR3C2 P08235 148 MAPK14 Q16539 239 IGHG1 P01857 330 CDK2 P24941 58 ADRB2 P07550 149 CDK2 P24941 240 PRSS1 P07477 331 LTA4H P09960 59 AKR1B1 P15121...”
• Mechanism of Peitu Shengjin Formula Shenlingbaizhu Powder in Treating Bronchial Asthma and Allergic Colitis through Different Diseases with Simultaneous Treatment Based on Network Pharmacology and Molecular Docking
  Zeng, Evidence-based complementary and alternative medicine : eCAM 2022
  • “...Adiponectin ADIPOQ Q15848 74 Cytochrome P450 1B1 CYP1B1 Q16678 149 Retinoic acid receptor RXR-beta RXRB P28702 75 Neuronal acetylcholine receptor protein, alpha-7 chain CHRNA7 P36544 Table 3 Active compounds related to key targets. Code Molecule ID Molecule name OB (%) DL Degree Herbs P172 MOL000098 Quercetin...”
• Network Pharmacology Analyses of the Pharmacological Targets and Therapeutic Mechanisms of Salvianolic Acid A in Myocardial Infarction
  Huang, Evidence-based complementary and alternative medicine : eCAM 2022
  • “...reductase-thymidylate synthase P05364 Beta-lactamase O00763 Acetyl-CoA carboxylase 2 Q04609 Glutamate carboxypeptidase 2 P16257 Translocator protein P28702 Retinoic acid receptor RXR-beta P00375 Dihydrofolate reductase P26684 Endothelin-1 receptor Q9QYJ6 cAMP and cAMP-inhibited cGMP 3,5-cyclic phosphodiesterase 10A Q9UHL4 Dipeptidyl peptidase 2 P20292 Arachidonate 5-lipoxygenase-activating protein P62943 Peptidyl-prolyl cis-trans isomerase...”
• Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects
  Gangwar, Pharmaceuticals (Basel, Switzerland) 2022
  • “...(Uniprot ID: P13631), ( E ) i. RXR (Uniprot ID: P19793), ii. RXR (Uniprot ID: P28702), iii. RXR (Uniprot ID: P48443), ( F ) VDR (Uniprot ID: P11473), ( G ) ERR (Uniprot ID: P11474), ( H ) i. FXR1 (Uniprot ID: P51114), ii. FXR2 (Uniprot...”
• Demystifying the Functional Role of Nuclear Receptors in Esophageal Cancer.
  Jayaprakash, International journal of molecular sciences 2022
  • “...receptor alpha (RXR ) (UniProt ID: P19793), Retinoid X receptor beta (RXR ) (UniProt ID: P28702), Retinoid X receptor gamma (RXR ) (UniProt ID: P48443) and Vitamin D receptors (VDRs) (UniProt ID: P11473). These proteins primary structures were taken from the UniProt database. Using the AlphaFold...”
• More

XP_009301491 nuclear receptor ROR-alpha B isoform X1 from Danio rerio
63% identity, 14% coverage

• Expression of zebrafish ROR alpha gene in cerebellar-like structures.
  Katsuyama, Developmental dynamics : an official publication of the American Association of Anatomists 2007 (PubMed)
  • GeneRIF: study reports cloning and expression pattern of zebrafish ROR alpha orthologues rora1 and rora2; both rora1 and rora2 are spatially expressed in the retina and tectum

XP_042101645 nuclear receptor subfamily 6 group A member 1 isoform X1 from Ovis aries
55% identity, 15% coverage

• Association analysis of polymorphism in the NR6A1 gene with the lumbar vertebrae number traits in sheep.
  Zhang, Genes & genomics 2019 (PubMed)
  • GeneRIF: The NR6A1 gene was considered as an important candidate for influence vertebrae number. SNP (rs414302710: A>C) locus of exon-8 of NR6A1 gene in sheep possible influence the number of lumbar vertebrae, which has the potential to be applied in selective breeding of sheep.

XP_005665914 retinoic acid receptor RXR-beta isoform X1 from Sus scrofa
55% identity, 14% coverage

• Cellular microRNA miR-c89 inhibits replication of porcine reproductive and respiratory syndrome virus by targeting the host factor porcine retinoid X receptor β.
  Zhang, The Journal of general virology 2019 (PubMed)
  • GeneRIF: MiR-89 directly targeted the 3'UTR of porcine retinoid X receptor beta (RXRB) mRNA in a sequence-specific manner.

NP_001158348 peroxisome proliferator-activated receptor gamma from Oryzias latipes
62% identity, 14% coverage

• The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: implications for developing new model organisms
  Kaur, PloS one 2015
  • “...NP_035276; M . musculus NP_035275; Oryzias latipus XP_004069934; O . latipus NP_001265836; O . latipus NP_001158348; B . glabrata 1 Contig2052; B . glabrata 2 Contig1275; L . gigantea 1 ProteinID174409; L . gigantea 2 ProteinID238472; H . sapiens ROR AAH0883. Scale bar, 0.1 expected changes/site....”

RORG_HUMAN / P51449 Nuclear receptor ROR-gamma; Nuclear receptor RZR-gamma; Nuclear receptor subfamily 1 group F member 3; RAR-related orphan receptor C; Retinoid-related orphan receptor-gamma from Homo sapiens (Human) (see 10 papers)
62% identity, 14% coverage

• function: Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism (PubMed:19381306, PubMed:19965867, PubMed:20203100, PubMed:22789990, PubMed:26160376). Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25- hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively (PubMed:19965867, PubMed:22789990). Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates the circadian expression of clock genes such as CRY1, BMAL1 and NR1D1 in peripheral tissues and in a tissue-selective manner. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORC-mediated activation of the expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A (PubMed:19965867). Negative regulator of adipocyte differentiation through the regulation of early phase genes expression, such as MMP3. Controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. In liver, has specific and redundant functions with RORA as positive or negative modulator of expression of genes encoding phase I and Phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as SULT1E1. Also plays a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC1 and PCK1 (PubMed:19965867). Regulates the rhythmic expression of PROX1 and promotes its nuclear localization (PubMed:19381306, PubMed:19965867, PubMed:20203100, PubMed:22789990, PubMed:26160376). Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity (PubMed:26160376).
  function: [Isoform 2]: Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyer's patches. Required for the generation of LTi (lymphoid tissue inducer) cells. Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2. Also plays a key role, downstream of IL6 and TGFB and synergistically with RORA, for lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. May also play a role in the pre-TCR activation cascade leading to the maturation of alpha/beta T-cells and may participate in the regulation of DNA accessibility in the TCR- J(alpha) locus.
  subunit: Interacts (via AF-2 motif) with the coactivator NCOA2 (via LXXLL motif) (PubMed:20211758). Interacts with the corepressor NCOR1 (By similarity). Interacts with CRY1 (PubMed:22170608). Interacts (via AF-2 motif) with the coactivators NCOA1 and PPARGC1A (via LXXLL motif) (By similarity). Interacts (via AF-2 motif) with PROX1 (By similarity). Interacts with FOXP3 (PubMed:18368049). Interacts with NR0B2 (By similarity).
• Exploring the mechanism of action of Lobetyolin in the treatment of allergic rhinitis based on network pharmacology and molecular docking
  Hou, Medicine 2025
  • “...A-4 hydrolase P09960 49 PLAU Urokinase-type plasminogen activator P00749 50 RORC Rar-related orphan receptor gamma P51449 51 EP300 istone acetyltransferase p300 Q09472 52 ITK Tyrosine-protein kinase ITK/TSK Q08881 53 PTGS1 Prostaglandin G/H synthase 1 P23219 54 HTR2A 5-Hydroxytryptamine receptor 2A P28223 55 NOS2 Nitric-oxide synthase, inducible...”
• BindingDB in 2024: a FAIR knowledgebase of protein-small molecule binding data.
  Liu, Nucleic acids research 2025
  • “...Q06187 23244 Bromodomain-containing protein 4 O60885 21446 Tyrosine-protein kinase JAK1 P23458 21217 Nuclear receptor ROR-gamma P51449 18532 Potassium voltage-gated channel subfamily H member 2 Q12809 17918 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform O00329 17663 Non-receptor tyrosine-protein kinase TYK2 P29597 17097 D(2) dopamine receptor P14416 16573...”
• Improving prediction performance of general protein language model by domain-adaptive pretraining on DNA-binding protein.
  Zeng, Nature communications 2024
  • “...HMG box, Homeobox, Fork-head, bHLH, and bZIP, as well as one multi-DBD TF (UniProt ID: P51449) containing two domains, i.e., Nuclear receptor and NR LBD, are used as demonstration cases. By looking at Fig. 4b , the most intuitive feeling is that those residues in the...”
  • “...residues in the DBD region in most cases. From the results of the multi-domain protein P51449, residues within both domains positively influence the final prediction, indicating that ESM-DBP not only probes the knowledge of single-domain proteins but also captures the specificity information of different DBDs of...”
• Exploring the pharmacological and adverse reaction mechanism of a drug by network pharmacology strategy: Using colchicine to treat Behcet syndrome as an example
  Li, Medicine 2023
  • “...O15553 MEFV Pyrin Homo sapiens P17948 FLT1 Vascular endothelial growth factor receptor 1 Homo sapiens P51449 RORC Nuclear receptor ROR-gamma Homo sapiens P08183 ABCB1 ATP-dependent translocase ABCB1 Homo sapiens BS = Behcet syndrome, COLC = colchicines, CXCL8 = interleukin-8, IL18 = interleukin-18, ITGA4 = integrin alpha-4,...”
• DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization
  Zhang, Scientific reports 2022
  • “...G protein-coupled receptor 0.095623787 DHODH Q02127 CHEMBL1966 Oxidoreductase 0.095623787 ATM Q13315 CHEMBL3797 Kinase 0.095623787 RORC P51449 CHEMBL1741186 Nuclear receptor 0.095623787 GRIN2A/GRIN1 Q12879/Q05586 CHEMBL1907604 Ligand-gated ion channel 0.095623787 SLC6A9 P48067 CHEMBL2337 Electrochemical transporter 0.095623787 NR1H3 Q13133 CHEMBL2808 Nuclear receptor 0.095623787 BDKRB2 P30411 CHEMBL3157 Family A G protein-coupled...”
• wSDTNBI: a novel network-based inference method for virtual screening
  Wu, Chemical science 2022
  • “...best wSDTNBI model Global-wSDTNBI-FCFP_4 was used to perform network-based VS on RORt (UniProt accession number: P51449, gene symbol: RORC). At first, a chemical library containing 730 natural products was obtained from TargetMol (Catalog No. L6000). After generating FCFP_4 fingerprints for compounds outside the global DTI network,...”
  • “...predicted interactions with these targets. Ten of the targets, such as RORt (UniProt accession number: P51449, gene symbol: RORC), were connected with more than 100 approved drugs. Our drugtargetimmunological process network may help to explain the molecular mechanisms of the effects of approved drugs on immunological...”
• Statistical Analysis of Protein-Ligand Interaction Patterns in Nuclear Receptor RORγ.
  Pham, Frontiers in molecular biosciences 2022
  • “...them are from gibbon ROR, which only contains a double substitution (K469A/R473A) from human UNP P51449. Another 34 PDBs are single point mutants at C455 (mostly C455S, occasionally CH or CE mutations were reported). By visual inspection, these mutations or substitutions are far from the ligand...”
  • “...The protein contains 243 residues with internal indices (1243) corresponding to the standard ROR (UniProt: P51449) A265S507. The AMBER14SB forcefield was used for the protein molecules of the simulation, whereas the TIP3P model was used to solvate the system with 11,622 water molecules in a rectangular...”
• Systems biology and artificial intelligence analysis highlights the pleiotropic effect of IVIg therapy in autoimmune diseases with a predominant role on B cells and complement system.
  Segú-Vergés, Frontiers in immunology 2022
  • “...PLCG2 ( 68 ) P35354 Prostaglandin G/H synthase 2 PTGS2 ( 1 , 78 ) P51449 Nuclear receptor ROR-gamma RORC ( 79 ) P05109 Protein S100-A8 S100A8 ( 80 ) P06702 Protein S100-A9 S100A9 ( 80 ) P16581 E-selectin SELE ( 72 , 73 ) P16109...”
• More

4nqaH / P19793 Crystal structure of liganded hrxr-alpha/hlxr-beta heterodimer on DNA (see paper)
57% identity, 23% coverage

• Ligands: peptide; dna; (9cis)-retinoic acid; zinc ion (4nqaH)

NR1D1_MOUSE / Q3UV55 Nuclear receptor subfamily 1 group D member 1; Rev-erbA-alpha; V-erbA-related protein 1; EAR-1 from Mus musculus (Mouse) (see 37 papers)
NP_663409 nuclear receptor subfamily 1 group D member 1 from Mus musculus
62% identity, 12% coverage

• function: Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC1 and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha- cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose- induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent manner. Represses the transcription of CYP2B10, CYP4A10 and CYP4A14 (PubMed:30555544). Represses the transcription of CES2 (PubMed:29653076). Represses and regulates the circadian expression of TSHB in a NCOR1-dependent manner (PubMed:24794873). Negatively regulates the protein stability of NR3C1 and influences the time- dependent subcellular distribution of NR3C1, thereby affecting its transcriptional regulatory activity (PubMed:27686098). Plays a critical role in the circadian control of neutrophilic inflammation in the lung; under resting, non-stress conditions, acts as a rhythmic repressor to limit inflammatory activity whereas in the presence of inflammatory triggers undergoes ubiquitin-mediated degradation thereby relieving inhibition of the inflammatory response (PubMed:29533925). Plays a key role in the circadian regulation of microglial activation and neuroinflammation; suppresses microglial activation through the NF- kappaB pathway in the central nervous system (PubMed:30792350). Plays a role in the regulation of the diurnal rhythms of lipid and protein metabolism in the skeletal muscle via transcriptional repression of genes controlling lipid and amino acid metabolism in the muscle (PubMed:30096135).
  subunit: Binds DNA as a monomer or a homodimer (By similarity). Interacts with NR2E3 and ZNHIT1 (By similarity). Interacts with C1D (PubMed:9405624). Interacts with SP1 (PubMed:22549838). Interacts with OPHN1 (via C-terminus) (PubMed:21874017). Interacts with PER2; the interaction associates PER2 to BMAL1 promoter region (PubMed:20159955, PubMed:22170608). Interacts with CRY1 (By similarity). Interacts with CCAR2 (PubMed:23398316). Interacts with SIAH2 (By similarity). Interacts with FBXW7 and CDK1 (PubMed:27238018). Interacts with HUWE1 (By similarity). Interacts with NR0B2 (PubMed:25212631, PubMed:30555544). Interacts with NFIL3 (PubMed:29653076). Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (PubMed:27686098).
  disruption phenotype: Mice display increased cold tolerance, higher oxygen consumption rates, enhanced brown adipose tissue metabolic capacity, maintenance of higher body temperature throughout the light phase and increased glucose uptake only during the day. They also show retinal abnormalities such as pan-retinal spotting and decreased response to light and decreased bile acid accumulation. Double knockout for NR1D1 and PER2 show a significantly shorter period length compared with wild type or single knockouts for both genes. 50% of double knockouts animals show a stable circadian throughout at least 5 weeks in constant darkness. The other 50% of animals lose their circadian rhythmicity when held in constant darkness for an average of 21 days. Animals have blunted steady-state levels of glycogen in the liver in spite of normal patterns of food consumption. Mice show exaggerated pulmonary inflammatory responses (PubMed:29533925). Mice display enhanced spontaneous hippocampal microglial and astrocyte activation, increased microglial NF-kappaB signaling and exacerbated LPS-induced neuroinflammation in the hippocampus (PubMed:30792350). Conditional knockout of both NR1D1 and NR1D2 in bronchiolar epithelial cells abolished diurnal rhythmicity of PER2 in the bronchioles and increased inflammatory responses and chemokine activation (PubMed:29533925).
• Rev-erbα attenuates diabetic myocardial injury through regulation of ferroptosis.
  Tian, Cellular signalling 2024 (PubMed)
  • GeneRIF: Rev-erbalpha attenuates diabetic myocardial injury through regulation of ferroptosis.
• Nuclear receptor Rev-erbα role in fine-tuning erythropoietin gene expression.
  Kumar, Blood advances 2024
  • GeneRIF: Nuclear receptor Rev-erbalpha role in fine-tuning erythropoietin gene expression.
• Role of the circadian nuclear receptor REV-ERBα in dorsal raphe serotonin synthesis in mood regulation.
  Park, Communications biology 2024
  • GeneRIF: Role of the circadian nuclear receptor REV-ERBalpha in dorsal raphe serotonin synthesis in mood regulation.
• Inhibition of mPGES-2 ameliorates NASH by activating NR1D1 via heme.
  Zhong, Hepatology (Baltimore, Md.) 2023 (PubMed)
  • GeneRIF: Inhibition of mPGES-2 ameliorates NASH by activating NR1D1 via heme.
• Nuclear receptor subfamily 1 group D member 1 in the pathology of obesity-induced osteoarthritis progression.
  Hosokawa, Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2023 (PubMed)
  • GeneRIF: Nuclear receptor subfamily 1 group D member 1 in the pathology of obesity-induced osteoarthritis progression.
• m6A methylation-induced NR1D1 ablation disrupts the HSC circadian clock and promotes hepatic fibrosis.
  Chen, Pharmacological research 2023 (PubMed)
  • GeneRIF: m[6]A methylation-induced NR1D1 ablation disrupts the HSC circadian clock and promotes hepatic fibrosis.
• NR1D1 Stimulates Antitumor Immune Responses in Breast Cancer by Activating cGAS-STING Signaling.
  Ka, Cancer research 2023
  • GeneRIF: NR1D1 Stimulates Antitumor Immune Responses in Breast Cancer by Activating cGAS-STING Signaling.
• Impact of the circadian nuclear receptor REV-ERBα in dorsal raphe 5-HT neurons on social interaction behavior, especially social preference.
  Jang, Experimental & molecular medicine 2023
  • GeneRIF: Impact of the circadian nuclear receptor REV-ERBalpha in dorsal raphe 5-HT neurons on social interaction behavior, especially social preference.
• More
• RNA sequencing indicates widespread conservation of circadian clocks in marine zooplankton
  Raghavan, NAR genomics and bioinformatics 2023
  • “...DBP (Q60925), HLF (Q8BW74), TEF (Q9JLC6) VRI (Dm Q9VMS4) Mm: NFIL3 (O08750) Mammalian REV-ERBa (Mm Q3UV55) Dm: EIP75B (P13055) RORa (Mm P51448) Dm: HR3 (P31396) Indicated in the left column are the baits, and in the right their counterparts. Alongside the protein name of the bait...”

NR1D1_HUMAN / P20393 Nuclear receptor subfamily 1 group D member 1; Rev-erbA-alpha; V-erbA-related protein 1; EAR-1 from Homo sapiens (Human) (see 18 papers)
NP_068370 nuclear receptor subfamily 1 group D member 1 from Homo sapiens
62% identity, 12% coverage

• function: Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC1 and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha- cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose- induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent manner. Represses the transcription of CYP2B10, CYP4A10 and CYP4A14 (By similarity). Represses the transcription of CES2 (By similarity). Represses and regulates the circadian expression of TSHB in a NCOR1- dependent manner (By similarity). Negatively regulates the protein stability of NR3C1 and influences the time-dependent subcellular distribution of NR3C1, thereby affecting its transcriptional regulatory activity (By similarity). Plays a critical role in the circadian control of neutrophilic inflammation in the lung; under resting, non- stress conditions, acts as a rhythmic repressor to limit inflammatory activity whereas in the presence of inflammatory triggers undergoes ubiquitin-mediated degradation thereby relieving inhibition of the inflammatory response (By similarity). Plays a key role in the circadian regulation of microglial activation and neuroinflammation; suppresses microglial activation through the NF-kappaB pathway in the central nervous system (By similarity). Plays a role in the regulation of the diurnal rhythms of lipid and protein metabolism in the skeletal muscle via transcriptional repression of genes controlling lipid and amino acid metabolism in the muscle (By similarity).
  subunit: Binds DNA as a monomer or a homodimer (PubMed:9660968). Interacts with C1D, NR2E3 and SP1 (By similarity). Interacts with OPHN1 (via C-terminus) (PubMed:21874017). Interacts with ZNHIT1 (PubMed:17892483). Interacts with PER2; the interaction associates PER2 to BMAL1 promoter region (PubMed:22170608). Interacts with CRY1 (PubMed:22170608). Interacts with CCAR2 (PubMed:23398316). Interacts with SIAH2 (PubMed:26392558). Interacts with CDK1 (By similarity). Interacts with FBXW7 (PubMed:27238018). Interacts with HUWE1 (PubMed:20534529). Interacts with NR0B2 (By similarity). Interacts with NFIL3 (By similarity). Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (By similarity).
• In silico prediction of heme binding in proteins
  Marson, The Journal of biological chemistry 2024
  • “...No Nuclear receptor subfamily 1 group D member 1 (Rev-erb) d Homo sapiens 3N00 e P20393 Nuclear receptor Yes Bovine serum albumin (BSA) Bos taurus 3V03 P02769 Plasma protein n.a. Human serum albumin (HSA) Homo sapiens 1N5U ; 1O9X P02768 Plasma protein; heme scavenging n.a. a...”
  • “...heme binding in this region. The heme-binding residues identified by ProFunc for Rev-erb (UniProt ID P20393 ) are Phe477, His602, and Glu604, all of which are located on -helices, Figure5 F . His602 has previously been identified as a heme binding residue ( 38 ). The...”
• Integrative Analysis of Proteomics and Transcriptomics Reveals Endothelin Receptor B as Novel Single Target and Identifies New Combinatorial Targets for Multiple Myeloma.
  Lejeune, HemaSphere 2023
  • “...Vitamin D3 receptor ICAM2 P13598 Intercellular adhesion molecule 2 (CD102) EPOR P19235 Erythropoietin receptor NR1D1 P20393 Nuclear receptor subfamily 1 group D member 1 ETB P24530 Endothelin receptor type B CD27 P26842 CD27 antigen IL5RA Q01344 IL-5R subunit alpha (CD125) BCMA Q02223 Tumor necrosis factor receptor...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2021
  • “...167 : 1220 [PMID:27893989] Nomenclature RevErb RevErb Systematic nomenclature NR1D1 NR1D2 HGNC, UniProt NR1D1 , P20393 NR1D2 , Q14995 Endogenous agonists heme [ 119 , 160 ] heme [ 95 , 119 , 160 ] Selective agonists GSK4112 [ 52 ], GSK4112 [ 71 ] Selective...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2017
  • “...be activated by heme. Nomenclature RevErb RevErb Systematic nomenclature NR1D1 NR1D2 HGNC, UniProt NR1D1 , P20393 NR1D2 , Q14995 Endogenous agonists heme [ 121 , 160 ] heme [ 97 , 121 , 160 ] Selective agonists GSK4112 [ 51 ], GSK4112 [ 70 ] Selective...”
• Representing and querying disease networks using graph databases.
  Lysenko, BioData mining 2016
  • “...path queries to explore relationships between a) the O15534 protein (PER1 gene) and b) the P20393 protein (REV-ErbA-alpha gene) and the circadian core genes, (Table 3 ). a In terms of distance in graph, the O15534 protein (PER1 gene) (red square), transcriptional repressor, is closer to...”
  • “...(NPAS2), (transcriptional activators). The circadian core genes are shown by black squares . b The P20393 protein (REV-ErbA-alpha gene) ( red square ), suggested to be involved in the disruption of clock genes [ 27 ], can be seen 3 steps away from the O00327(ARNTL/BMAL1) and...”
• ACTP: A webserver for predicting potential targets and relevant pathways of autophagy-modulating compounds.
  Xie, Oncotarget 2016
• De Novo and Rare Variants at Multiple Loci Support the Oligogenic Origins of Atrioventricular Septal Heart Defects.
  Priest, PLoS genetics 2016
  • “...conserved arginine residue. The relevant portion of a protein sequence alignment of Q6NSM0 (NR1D2) and P20393 (NR1D1) from UniProt.org (accessed 4/7/15) using standard parameters is shown. The DNA binding domains of the two proteins are delineated by the black text and display 96% sequence identity. The...”
• The Concise Guide to PHARMACOLOGY 2015/16: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2015
  • “...be activated by heme. Nomenclature RevErb RevErb Systematic nomenclature NR1D1 NR1D2 HGNC, UniProt NR1D1 , P20393 NR1D2 , Q14995 Endogenous agonists heme (Selective) [ 122 , 164 ] heme (Selective) [ 122 , 164 ] Selective agonists GSK4112 (pEC 50 6.4) [ 51 ], GSK4112 (pIC...”
• More
• NR1D1-rearranged soft tissue tumour: A clinicopathological and molecular analysis of four additional cases.
  Yin, Histopathology 2024 (PubMed)
  • GeneRIF: NR1D1-rearranged soft tissue tumour: A clinicopathological and molecular analysis of four additional cases.
• Functional Characterization of Circadian Nuclear Receptors REV-ERBα and REV-ERBβ in Human Osteosarcoma Cell Cultures.
  Cho, International journal of molecular sciences 2024
  • GeneRIF: Functional Characterization of Circadian Nuclear Receptors REV-ERBalpha and REV-ERBbeta in Human Osteosarcoma Cell Cultures.
• Nuclear receptor Rev-erbα role in fine-tuning erythropoietin gene expression.
  Kumar, Blood advances 2024
  • GeneRIF: Nuclear receptor Rev-erbalpha role in fine-tuning erythropoietin gene expression.
• Functional inversion of circadian regulator REV-ERBα leads to tumorigenic gene reprogramming.
  Yang, Proceedings of the National Academy of Sciences of the United States of America 2024
  • GeneRIF: Functional inversion of circadian regulator REV-ERBalpha leads to tumorigenic gene reprogramming.
• Clock gene NR1D1 might be a novel target for the treatment of bladder cancer.
  Yang, Urologic oncology 2023 (PubMed)
  • GeneRIF: Clock gene NR1D1 might be a novel target for the treatment of bladder cancer.
• Uncovering the Novel Role of NR1D1 in Regulating BNIP3-Mediated Mitophagy in Ulcerative Colitis.
  Chen, International journal of molecular sciences 2023
  • GeneRIF: Uncovering the Novel Role of NR1D1 in Regulating BNIP3-Mediated Mitophagy in Ulcerative Colitis.
• Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBα genes with body mass index and lipid levels in children.
  Vales-Villamarín, Scientific reports 2023
  • GeneRIF: Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBalpha genes with body mass index and lipid levels in children.
• REV-ERBs negatively regulate mineralization of the cementoblasts.
  Fu, Biochemical and biophysical research communications 2022 (PubMed)
  • GeneRIF: REV-ERBs negatively regulate mineralization of the cementoblasts.
• More

XP_008191373 nuclear hormone receptor FTZ-F1 isoform X1 from Tribolium castaneum
59% identity, 13% coverage

• Role of nuclear receptors NlHR3 and NlFTZ-F1 in regulating molting and reproduction in Nilaparvata lugens (stål)
  Li, Frontiers in physiology 2023
  • “...humanus corporis , XP_002430379), TcFTZ-F1 ( Tribolium castaneum , EFA01263), TcFTZ-F1X1 ( Tribolium castaneum , XP_008191373), TcFTZ-F1X2 ( Tribolium castaneum , XP_008191374), TcFTZ-F1X3 ( Tribolium castaneum , XP_008191375), ApFTZ-F1X1 ( Acyrthosiphon pisum , XP_008183294), ApFTZ-F1X2 ( Acyrthosiphon pisum , XP_008183295), BgFTZ-F1 ( Blattella germanica , CAQ57670),...”

XP_008191374 nuclear hormone receptor FTZ-F1 isoform X2 from Tribolium castaneum
59% identity, 13% coverage

• Role of nuclear receptors NlHR3 and NlFTZ-F1 in regulating molting and reproduction in Nilaparvata lugens (stål)
  Li, Frontiers in physiology 2023
  • “...Tribolium castaneum , EFA01263), TcFTZ-F1X1 ( Tribolium castaneum , XP_008191373), TcFTZ-F1X2 ( Tribolium castaneum , XP_008191374), TcFTZ-F1X3 ( Tribolium castaneum , XP_008191375), ApFTZ-F1X1 ( Acyrthosiphon pisum , XP_008183294), ApFTZ-F1X2 ( Acyrthosiphon pisum , XP_008183295), BgFTZ-F1 ( Blattella germanica , CAQ57670), AaFTZ-F1a ( Aedes aegypti , XP_001654601),...”

RORAB_DANRE / F1QJF4 Nuclear receptor ROR-alpha B; Retinoid-related orphan receptor alpha 1; Retinoid-related orphan receptor-alpha B from Danio rerio (Zebrafish) (Brachydanio rerio) (see paper)
63% identity, 15% coverage

• function: Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) (By similarity). Required for proper cerebellum development (By similarity).

RXRB_RAT / P49743 Retinoic acid receptor RXR-beta; Nuclear receptor coregulator 1; Nuclear receptor subfamily 2 group B member 2; Retinoid X receptor beta from Rattus norvegicus (Rat) (see 2 papers)
55% identity, 16% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE).
  subunit: Homodimer (in vitro) (By similarity). Heterodimer with other retinoic acid receptor family members. Binds DNA preferentially as a RAR/RXR heterodimer (PubMed:1662118). Interacts with NR1H3 (By similarity). Interacts with AKAP13 (By similarity).
• PPAR beta/gamma mediates the antihypertensive activity of a synbiotic preparation of Bifidobacterium lactis and Lactobacillus acidophilus in spontaneous hypertensive rats
  Huang, Heliyon 2024
  • “...2.9648 0.0352 0.5152 0.5355 70 Q6TA48 Mucosal pentraxin MPTX 4 3.6308 0.0247 1.3932 0.5832 71 P49743 Retinoic acid receptor RXR-beta RXRB 2 0.6026 0.0414 1.5417 0.0454 Table 5 71 differentially expressed proteins in the ileum between the model and control group ( P (M/C)<0.05) were determined...”
  • “...(Apoa1) lipid transporter activity, phospholipid binding, lipid binding P18886 carnitine palmitoyltransferase 2(Cpt2) Carnitine O-palmitoyltransferase activity P49743 Retinoic acid receptor RXR-beta ligand-activated sequence-specific DNA binding, steroid hormone receptor activity Table 6 Compared with the WKYs, six differentially expressed proteins involved in PPAR signaling pathway were determined in...”
• A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion.
  Mitsios, BMC neuroscience 2007
  • “...U31367 Q64349 1.7-fold 2 6 0.2-fold 21 days Retinoic Acid Receptor beta M84820 P28702 M81766 P49743 2.0-fold 2 6 0.1-fold 21 days S54072 P28703 Tyrosine Phosphatase 1B M31724 P18031 M33962 P20417 3.4-fold 2 6 0.2-fold 21 days Adenosine A1 Receptor S56143 P30542 M64299 P25099 2.6-fold 2...”
• High-throughput identification of IMCD proteins using LC-MS/MS.
  Pisitkun, Physiological genomics 2006

RXRBB_DANRE / Q90417 Retinoic acid receptor RXR-beta-B; Nuclear receptor subfamily 2 group B member 2-B; Retinoic acid receptor RXR-delta; Retinoid X receptor beta-B; Retinoid X receptor delta from Danio rerio (Zebrafish) (Brachydanio rerio) (see 2 papers)
55% identity, 18% coverage

• function: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The rar/rxr heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for rxrs is 9-cis retinoic acid (By similarity).
  subunit: Homodimer (By similarity). Heterodimer; with a rar molecule (By similarity). Binds DNA preferentially as a rar/rxr heterodimer (By similarity). Heterodimerizes with rarga.

NP_001106893 nuclear receptor subfamily 1 group D member 1 isoform 1 from Rattus norvegicus
62% identity, 12% coverage

• Rev-erbα attenuates refractory periapical periodontitis via M1 polarization: An in vitro and in vivo study.
  Song, International endodontic journal 2024 (PubMed)
  • GeneRIF: Rev-erbalpha attenuates refractory periapical periodontitis via M1 polarization: An in vitro and in vivo study.
• PTZ-kindled rat model; evaluation of seizure, hippocampal EGR-1, and Rev-erbα gene regulation, behavioral analysis, and antioxidant capacity of Gum Arabic.
  Yakmaz, Molecular biology reports 2024 (PubMed)
  • GeneRIF: PTZ-kindled rat model; evaluation of seizure, hippocampal EGR-1, and Rev-erbalpha gene regulation, behavioral analysis, and antioxidant capacity of Gum Arabic.
• Regulation of Circadian Genes Nr1d1 and Nr1d2 in Sex-Different Manners during Liver Aging.
  Noh, International journal of molecular sciences 2022
  • GeneRIF: Regulation of Circadian Genes Nr1d1 and Nr1d2 in Sex-Different Manners during Liver Aging.
• Central administration of REV-ERBα agonist promotes opposite responses on energy balance in fasted and fed states.
  Borba, Journal of neuroendocrinology 2020 (PubMed)
  • GeneRIF: Central administration of REV-ERBalpha agonist promotes opposite responses on energy balance in fasted and fed states.
• The nuclear receptor REV-ERBα represses the transcription of growth/differentiation factor 10 and 15 genes in rat endometrium stromal cells.
  Zhao, Physiological reports 2016
  • GeneRIF: findings indicate that the attenuation of REV-ERBalpha leads to an upregulation of Gdf10 and Gdf15 in decidual cells
• Inhibitory role of REV-ERBα in the expression of bone morphogenetic protein gene family in rat uterus endometrium stromal cells.
  Tasaki, American journal of physiology. Cell physiology 2015 (PubMed)
  • GeneRIF: Bone morphogenetic protein gene expression is inhibited by REV-ERBalpha which acts as a transcriptional silencer.
• Removal of Rev-erbα inhibition contributes to the prostaglandin G/H synthase 2 expression in rat endometrial stromal cells.
  Isayama, American journal of physiology. Endocrinology and metabolism 2015 (PubMed)
  • GeneRIF: Data (including data from studies in transgenic rats) suggest attenuation of circadian clock system, especially Rev-erb-alpha, contributes to induction of prostaglandin G/H synthase 2 in endometrial stromal cells during decidualization/placentation.
• Integration of the nuclear receptor REV-ERBα linked with circadian oscillators in the expressions of Alas1, Ppargc1a, and Il6 genes in rat granulosa cells.
  Chen, Chronobiology international 2015 (PubMed)
  • GeneRIF: REV-ERBalpha has a role in circadian oscillation in the expressions of Alas1, Ppargc1a, and Il6 genes in rat granulosa cells
• More

B3SV56 Nuclear receptor subfamily 1 group D member 1 from Ovis aries
62% identity, 12% coverage

• Characterisation of the circulating acellular proteome of healthy sheep using LC-MS/MS-based proteomics analysis of serum
  Chemonges, Proteome science 2016
  • “...were uncharacterised. Of the 74 annotated proteins, only annexin A2 (P14639), serum albumin (P12303), transthyretin (B3SV56), nuclear receptor subfamily 1 group D member 1 (A2SW69) and insulin-like growth factor-binding protein 2a (Q29400) had been reviewed and therefore included in the Swiss-Prot subset of UniProtKB. The unreviewed,...”

NR1D1_RAT / Q63503 Nuclear receptor subfamily 1 group D member 1; Rev-erbA-alpha; V-erbA-related protein 1; EAR-1 from Rattus norvegicus (Rat) (see 3 papers)
62% identity, 12% coverage

• function: Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC1 and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha- cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose- induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator (By similarity). In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis (PubMed:22425774). In collaboration with SP1, activates GJA1 transcription in a heme-independent manner (By similarity). Represses the transcription of CYP2B10, CYP4A10 and CYP4A14 (By similarity). Represses the transcription of CES2 (By similarity). Represses and regulates the circadian expression of TSHB in a NCOR1- dependent manner (By similarity). Negatively regulates the protein stability of NR3C1 and influences the time-dependent subcellular distribution of NR3C1, thereby affecting its transcriptional regulatory activity (By similarity). Plays a critical role in the circadian control of neutrophilic inflammation in the lung; under resting, non- stress conditions, acts as a rhythmic repressor to limit inflammatory activity whereas in the presence of inflammatory triggers undergoes ubiquitin-mediated degradation thereby relieving inhibition of the inflammatory response (By similarity). Plays a key role in the circadian regulation of microglial activation and neuroinflammation; suppresses microglial activation through the NF-kappaB pathway in the central nervous system (By similarity). Plays a role in the regulation of the diurnal rhythms of lipid and protein metabolism in the skeletal muscle via transcriptional repression of genes controlling lipid and amino acid metabolism in the muscle (By similarity).
  subunit: Binds DNA as a monomer or a homodimer (By similarity). Interacts with C1D, NR2E3, SP1 and ZNHIT1 (By similarity). Interacts with OPHN1 (via C-terminus) (PubMed:21874017). Interacts with PER2; the interaction associates PER2 to BMAL1 promoter region (By similarity). Interacts with CRY1 (By similarity). Interacts with CCAR2 (By similarity). Interacts with SIAH2 (By similarity). Interacts with FBXW7 and CDK1 (By similarity). Interacts with HUWE1 (By similarity). Interacts with NR0B2 (By similarity). Interacts with NFIL3 (By similarity). Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (By similarity).

NR1D1_BOVIN / Q08E02 Nuclear receptor subfamily 1 group D member 1; Rev-erbA-alpha; V-erbA-related protein 1; EAR-1 from Bos taurus (Bovine) (see paper)
NP_001071568 nuclear receptor subfamily 1 group D member 1 from Bos taurus
62% identity, 12% coverage

• function: Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC1 and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha- cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose- induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent manner (By similarity). Represses the transcription of CYP2B10, CYP4A10 and CYP4A14 (By similarity). Represses the transcription of CES2 (By similarity). Represses and regulates the circadian expression of TSHB in a NCOR1-dependent manner (By similarity). Negatively regulates the protein stability of NR3C1 and influences the time-dependent subcellular distribution of NR3C1, thereby affecting its transcriptional regulatory activity (By similarity). Plays a critical role in the circadian control of neutrophilic inflammation in the lung; under resting, non-stress conditions, acts as a rhythmic repressor to limit inflammatory activity whereas in the presence of inflammatory triggers undergoes ubiquitin-mediated degradation thereby relieving inhibition of the inflammatory response (By similarity). Plays a key role in the circadian regulation of microglial activation and neuroinflammation; suppresses microglial activation through the NF- kappaB pathway in the central nervous system (By similarity). Plays a role in the regulation of the diurnal rhythms of lipid and protein metabolism in the skeletal muscle via transcriptional repression of genes controlling lipid and amino acid metabolism in the muscle (By similarity).
  subunit: Binds DNA as a monomer or a homodimer (By similarity). Interacts with C1D, SP1 and ZNHIT1 (By similarity). Interacts with OPHN1 (via C-terminus) (By similarity). Interacts with PER2; the interaction associates PER2 to BMAL1 promoter region (By similarity). Interacts with CRY1 (By similarity). Interacts with CCAR2 (By similarity). Interacts with NR2E3 (PubMed:15190009). Interacts with SIAH2 (By similarity). Interacts with FBXW7 and CDK1 (By similarity). Interacts with HUWE1 (By similarity). Interacts with NR0B2 (By similarity). Interacts with NFIL3 (By similarity). Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (By similarity).
• REV-ERBα inhibits the PTGS2 expression in bovine uterus endometrium stromal and epithelial cells exposed to ovarian steroids.
  Isayama, The Journal of reproduction and development 2014
  • GeneRIF: results indicate that nuclear receptor subfamily 1 group D member 1(REV-ERBalpha) plays an inhibitory role in the expression of prostaglandin G/H synthetase(PTGS2) in both bovine uterine stromal and epithelial cells treated with ovarian steroids
• Functional characterization of an orphan nuclear receptor, Rev-ErbAalpha, in chondrocytes and its potential role in osteoarthritis.
  Chaturvedi, Arthritis and rheumatism 2006 (PubMed)
  • GeneRIF: Rev-ErbAalpha is highly expressed in articular chondrocytes

NP_001193745 nuclear receptor subfamily 5 group A member 2 from Bos taurus
59% identity, 14% coverage

• Integrated Structural Modeling of Full-Length LRH-1 Reveals Inter-domain Interactions Contribute to Receptor Structure and Function
  Seacrist, Structure (London, England : 1993) 2020
  • “...Pan troglodytes LRH-1 (XP_001142695), Mus musculus LRH-1 (P45448), Rattus norvegicus LRH-1 (Q9QWM1), Bos taurus LRH-1 (NP_001193745), Equus caballus LRH-1 (XP_023488164), Sus scrofa LRH-1 (AFD98842), Danio rerio LRH-1 (AAI63522), Homo sapiens SF-1 (Q13285), Pan troglodytes SF-1 (XP_016817123), Mus musculus SF-1 (P33242), Rattus norvegicus SF-1 (P50569), Bos taurus...”

NP_035276 peroxisome proliferator-activated receptor gamma isoform 2 from Mus musculus
62% identity, 14% coverage

• The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: implications for developing new model organisms
  Kaur, PloS one 2015
  • “...AB32649; H . sapiens AAH06811; H . sapiens AAA36469; Mus musculus NP_035274; M . musculus NP_035276; M . musculus NP_035275; Oryzias latipus XP_004069934; O . latipus NP_001265836; O . latipus NP_001158348; B . glabrata 1 Contig2052; B . glabrata 2 Contig1275; L . gigantea 1 ProteinID174409;...”

NP_001019803 peroxisome proliferator-activated receptor gamma from Canis lupus familiaris
62% identity, 14% coverage

• Cytosolic phospholipase A2 regulates lipid homeostasis under osmotic stress through PPARγ.
  Parra, The FEBS journal 2024 (PubMed)
  • GeneRIF: Cytosolic phospholipase A2 regulates lipid homeostasis under osmotic stress through PPARgamma.
• Peroxisome proliferator-activated receptor γ modulates renal crystal retention associated with high oxalate concentration by regulating tubular epithelial cellular transdifferentiation.
  Li, Journal of cellular physiology 2019 (PubMed)
  • GeneRIF: our results revealed that endogenic PPARgamma activity plays a vital regulatory role in crystal clearance, subsequent crystal adherence, and CaOx stone formation via manipulating the transdifferentiation of renal tubular epithelial cells.
• Expression and functional implications of peroxisome proliferator-activated receptor gamma (PPARγ) in canine reproductive tissues during normal pregnancy and parturition and at antiprogestin induced abortion.
  Kowalewski, Theriogenology 2011 (PubMed)
  • GeneRIF: a regulatory role of peroxisome proliferator-activated receptor gamma (PPARgamma) in canine placental development possibly through influencing the invasion of fetal trophoblast cells is suggested
• Cloning, expression and investigation for polymorphisms of canine peroxisome proliferator-activated receptors.
  Nishii, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 2007 (PubMed)
  • GeneRIF: Investigations for polymorphisms of PPARgamma revealed a silent polymorphism, C1362T, in 3 of 92 dogs.

NP_851367 peroxisome proliferator-activated receptor gamma from Bos taurus
62% identity, 14% coverage

• Myostatin site-directed mutation and simultaneous PPARγ site-directed knockin in bovine genome.
  Ge, Journal of cellular physiology 2021 (PubMed)
  • GeneRIF: Myostatin site-directed mutation and simultaneous PPARgamma site-directed knockin in bovine genome.
• Bovine Stearoyl-CoA Desaturase 1 Promotes Adipogenesis by Activating the PPARγ Receptor.
  Zhang, Journal of agricultural and food chemistry 2020 (PubMed)
  • GeneRIF: Bovine Stearoyl-CoA Desaturase 1 Promotes Adipogenesis by Activating the PPARgamma Receptor.
• miR-454 regulates triglyceride synthesis in bovine mammary epithelial cells by targeting PPAR-γ.
  Zhang, Gene 2019 (PubMed)
  • GeneRIF: Results found that PPAR-gamma expression is regulated by miR-454 in bovine mammary epithelial cells (BMECs). miR-454 directly targets the 3'UTR of PPAR-gamma to regulate triglyceride synthesis in BMECs.
• mTORC2 Regulates Lipogenic Gene Expression through PPARγ to Control Lipid Synthesis in Bovine Mammary Epithelial Cells.
  Guo, BioMed research international 2019
  • GeneRIF: mTORC2 plays a critical role in regulating lipogenic gene expression, lipid synthesis, and secretion in bovine mammary epithelial cells, and this process probably is through PPARgamma.
• Two Novel SNPs of PPARγ Significantly Affect Weaning Growth Traits of Nanyang Cattle.
  Huang, Animal biotechnology 2018 (PubMed)
  • GeneRIF: Three novel SNPs of the bovine PPARgamma gene were identified in 514 individuals from six Chinese cattle breeds: SNP1 (AC_000179.1 g.57386668 C > G) in intron 2 and SNP2 (AC_000179.1 g.57431964 C > T) and SNP3 (AC_000179.1 g.57431994 T > C) in exon 7.
• Bta-miR-130a/b regulates preadipocyte differentiation by targeting PPARG and CYP2U1 in beef cattle.
  Ma, Molecular and cellular probes 2018 (PubMed)
  • GeneRIF: This study shows that bta-miR-130a and bta-miR-130b play similar roles in the regulation of adipocyte differentiation in beef muscles by targeting the 3'UTR of PPARG and CYP2U1.
• Docosahexaenoic acid attenuates LPS-stimulated inflammatory response by regulating the PPARγ/NF-κB pathways in primary bovine mammary epithelial cells.
  He, Research in veterinary science 2017 (PubMed)
  • GeneRIF: These results indicated that docosahexaenoic acid may attenuate lipopolysaccharide-stimulated inflammatory response in bovine mammary epithelial cells by suppressing NF-kappaB activation through a mechanism partly dependent on PPARgamma activation.
• Regulation of peroxisome proliferator-activated receptor gamma on milk fat synthesis in dairy cow mammary epithelial cells.
  Liu, In vitro cellular & developmental biology. Animal 2016 (PubMed)
  • GeneRIF: PPARgamma is a positive regulator of milk fat synthesis in dairy cow mammary epithelial cells.
• More

Q86WD1 Peroxisome proliferator-activated receptor gamma from Homo sapiens
62% identity, 12% coverage

• β'-COP mediated loading of PPARγ into trophoblast-derived extracellular vesicles
  Luo, Cellular and molecular life sciences : CMLS 2024
  • “...OS=Homo sapiens OX=9606 GN=PPARG PE=2 SV=1 48.12 29.63 1 1 14 19 1711 257.2 7.21 Q86WD1 HUMAN Peroxisome proliferator-activated receptor gamma OS=Homo sapiens OX=9606 GN=PPARG PE=2 SV=1 49.09 69.21 1 1 22 17 2074 397.7 8.47 P37231 HUMAN Peroxisome proliferator-activated receptor gamma OS=Homo sapiens OX=9606 GN=PPARG...”
  • “...OS=Homo sapiens OX=9606 GN=PPARG PE=2 SV=1 50.75 57.78 1 1 17 29 2711 239.2 5.22 Q86WD1 HUMAN Peroxisome proliferator-activated receptor gamma OS=Homo sapiens OX=9606 GN=PPARG PE=2 SV=1 69.22 49.59 1 1 16 27 2944 339.1 6.77 P37231 HUMAN Peroxisome proliferator-activated receptor gamma OS=Homo sapiens OX=9606 GN=PPARG...”

PPARG_MOUSE / P37238 Peroxisome proliferator-activated receptor gamma; PPAR-gamma; Nuclear receptor subfamily 1 group C member 3 from Mus musculus (Mouse) (see 19 papers)
62% identity, 14% coverage

• function: Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels (PubMed:19041764).
  subunit: Heterodimer with other nuclear receptors, such as RXRA. The heterodimer with the retinoic acid receptor RXRA is called adipocyte- specific transcription factor ARF6. Interacts with NCOA6 coactivator, leading to a strong increase in transcription of target genes. Interacts with coactivator PPARBP, leading to a mild increase in transcription of target genes. Interacts with NOCA7 in a ligand- inducible manner. Interacts with NCOA1 and NCOA2 LXXLL motifs. Interacts with ASXL1, ASXL2, DNTTIP2, FAM120B, MAP2K1/MEK1, NR0B2, PDPK1, PRDM16, PRMT2 and TGFB1I1. Interacts (when activated by agonist) with PPP5C. Interacts with HELZ2 and THRAP3; the interaction stimulates the transcriptional activity of PPARG. Interacts with PER2, the interaction is ligand dependent and blocks PPARG recruitment to target promoters. Interacts with NOCT. Interacts with FOXO1 (acetylated form). Interacts with ACTN4 (By similarity). Interacts (when in the liganded conformation) with GPS2 (PubMed:25519902). Interacts with CRY1 and CRY2 in a ligand-dependent manner (PubMed:28683290). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863). In macrophages, interacts with PAQR3 and STUB1; the interactions promote PPARG poylubiquitination and STUB1-mediated degradation (PubMed:35710596).
  disruption phenotype: Mice develop abnormalities in circadian variations in blood pressure and heart rate, in parallel with a reduction of diurnal variations in the sympathetic nerve activity, and impaired rhythmicity of BMAL1 in the blood vessels.
• Modulation of adiposity and adipocyte inflammation by methanol extracts of Alpinia calcarata leaf in high-fat-diet induced-obese mice: Involvement of COX-2 and PPAR-γ
  Ahmad, Heliyon 2025
  • “...1 Compounds PubChem ID Receptors Uniprot ID Carotol 442347 COX-2 Q05769 1,8 cineole 2758 PPAR P37238 -pinene 14896 IL-6 P08505 Camphor 2537 GLUT-4 P14142 Methyl cinnamate 637520 2.2 Plant extract preparation The desired plant leaves of A. calcarata were harvested from botanical garden in Dhaka, Bangladesh....”
• The effect of G0S2 on insulin sensitivity: A proteomic analysis in a G0S2-overexpressed high-fat diet mouse model.
  Wu, Frontiers in endocrinology 2023
  • “...S-transferase P 1 Gstp1 0.563400004 down Q60631 Growth factor receptor-bound protein 2 Grb2 0.526383608 down P37238 Peroxisome proliferator-activated receptor gamma Pparg 0.397358829 Up, upregulated; down, downregulated. Figure6 Insulin resistance was evaluated using western blotting and RT-PCR analysis. Upregulation of phosphatase Foxo1, Socs3, and Ptpn1, and downregulation...”

PPARG_RAT / O88275 Peroxisome proliferator-activated receptor gamma; PPAR-gamma; Nuclear receptor subfamily 1 group C member 3 from Rattus norvegicus (Rat) (see 3 papers)
62% identity, 14% coverage

• function: Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels.
  subunit: Interacts with FOXO1 (acetylated form) (By similarity). Heterodimer with other nuclear receptors, such as RXRA. The heterodimer with the retinoic acid receptor RXRA is called adipocyte-specific transcription factor ARF6. Interacts with NCOA6 coactivator, leading to a strong increase in transcription of target genes. Interacts with coactivator PPARBP, leading to a mild increase in transcription of target genes. Interacts with NOCA7 in a ligand-inducible manner. Interacts with NCOA1 and NCOA2 LXXLL motifs. Interacts with ASXL1, ASXL2, DNTTIP2, FAM120B, MAP2K1/MEK1, NR0B2, PDPK1, PRDM16, PRMT2 and TGFB1I1. Interacts (when activated by agonist) with PPP5C. Interacts with HELZ2 and THRAP3; the interaction stimulates the transcriptional activity of PPARG. Interacts with PER2, the interaction is ligand dependent and blocks PPARG recruitment to target promoters. Interacts with NOCT. Interacts with ACTN4. Interacts (when in the liganded conformation) with GPS2 (By similarity). Interacts with CRY1 and CRY2 in a ligand-dependent manner (By similarity). In the absence of hormonal ligand, interacts with TACC1 (By similarity). In macrophages, interacts with PAQR3 and STUB1; the interactions promote PPARG poylubiquitination and STUB1-mediated degradation (By similarity).
• Analysis of long noncoding RNA-associated competing endogenous RNA network in glucagon-like peptide-1 receptor agonist-mediated protection in β cells
  Cui, World journal of diabetes 2020
  • “...receptor Hmgcr P51639 Enzyme Mme P07861 Enzyme Oprm1 P33535 Family A G protein-coupled receptor Pparg O88275 Nuclear receptor Prkcg P63319 Structural protein Ptgs2 P35355 Family A G protein-coupled receptor Pygl P09811 Enzyme Ren1 P08424 Family A G protein-coupled receptor Slc6a3 P23977 Electrochemical transporter Tert Q673L6 Enzyme...”
• Effects of Tocotrienols on Insulin Secretion-Associated Genes Expression of Rat Pancreatic Islets in a Dynamic Culture.
  Chia, Frontiers in pharmacology 2016
  • “...The amino acids sequences of rat PPAR (Accession Id: Q62879) and rat PPAR (Accession Id: O88275) were then retrieved from UniProtKB ( The UniProt Consortium, 2009 ). BLAST program was used to search for the suitable template structures in the Protein Data Bank (PDB) at National...”
• Functional genomics reveals increases in cholesterol biosynthetic genes and highly unsaturated fatty acid biosynthesis after dietary substitution of fish oil with vegetable oils in Atlantic salmon (Salmo salar).
  Leaver, BMC genomics 2008
  • “...protein 3 NAN. 0.489 0.709 0.652 (Q9BYV7) BCDO2 Beta-carotene dioxygenase 2 AJ416951 0.541 0.696 0.799 (O88275) Peroxisome proliferator-activated receptor gamma AM402843 0.362 0.67 0.441 (Q5TZ29) Novel protein similar to vertebrate apolipoprotein B CARBOHYDRATE METABOLISM CK880626 1.093 1.816 2.013 (P05370) G6PD Glucose-6-phosphate 1-dehydrogenase AM083390 2.685 1.291 1.873...”

PPARG_HUMAN / P37231 Peroxisome proliferator-activated receptor gamma; PPAR-gamma; Nuclear receptor subfamily 1 group C member 3 from Homo sapiens (Human) (see 33 papers)
NP_056953 peroxisome proliferator-activated receptor gamma isoform 2 from Homo sapiens
62% identity, 14% coverage

• function: Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels (By similarity).
  function: (Microbial infection) Upon treatment with M.tuberculosis or its lipoprotein LpqH, phosphorylation of MAPK p38 and IL-6 production are modulated, probably via this protein.
  subunit: Interacts with FOXO1 (acetylated form) (By similarity). Heterodimer with other nuclear receptors, such as RXRA. The heterodimer with the retinoic acid receptor RXRA is called adipocyte-specific transcription factor ARF6. Interacts with NCOA6 coactivator, leading to a strong increase in transcription of target genes. Interacts with coactivator PPARBP, leading to a mild increase in transcription of target genes. Interacts with NOCA7 in a ligand-inducible manner. Interacts with NCOA1 and NCOA2 LXXLL motifs. Interacts with ASXL1, ASXL2, DNTTIP2, FAM120B, MAP2K1/MEK1, NR0B2, PDPK1, PRDM16, PRMT2 and TGFB1I1. Interacts (when activated by agonist) with PPP5C. Interacts with HELZ2 and THRAP3; the interaction stimulates the transcriptional activity of PPARG. Interacts with PER2, the interaction is ligand dependent and blocks PPARG recruitment to target promoters. Interacts with NOCT. Interacts with ACTN4. Interacts (when in the liganded conformation) with GPS2 (By similarity). Interacts with CRY1 and CRY2 in a ligand-dependent manner (By similarity). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863). In macrophages, interacts with PAQR3 and STUB1; the interactions promote PPARG poylubiquitination and STUB1-mediated degradation (By similarity).
• Analysis of RXR/THR and RXR/PPARG2 heterodimerization by bioluminescence resonance energy transfer (BRET)
  Mulero, PloS one 2013
  • “...aas (starting Methionine 203), mouse THR, NP_835161 size 410aas (starting Methionine 1) and human PPARG2, NP_056953 size 505 aas (starting Methionine 1). We cloned Rluc8 and EYFP in N-terminus and C-terminus of RXR, THR and PPARG2. Preliminary experiments showed that the C-terminus fusion proteins gave more...”
• Construction and application of a precise evaluation method for the quality of traditional Chinese medicine based on "target-combined quality evaluation" using safflower as an example
  Zhou, Frontiers in pharmacology 2025 (no snippet)
• Aripiprazole alleviates the high prolactin levels induced by amisulpride via distinct molecular mechanisms: a network pharmacology and molecular docking study
  Yao, BMC psychiatry 2025
  • “...NO. Uniprot ID Gene Symbol Docking scores Mean Aripiprazole 1 P27361 MAPK3 9.4 8.1 2 P37231 PPARG 9.2 3 P02768 ALB 8.6 4 Q13224 GRIN2B 8.2 5 P49841 GSK3B 8.0 6 P03372 ESR1 7.8 7 P14416 DRD2 7.5 8 P42574 CASP3 7.3 9 P05019 IGF1 7.0...”
• Kaempferol Mitigates <i>Pseudomonas aeruginosa</i>-Induced Acute Lung Inflammation Through Suppressing GSK3β/JNK/c-Jun Signaling Pathway and NF-κB Activation
  Wang, Pharmaceuticals (Basel, Switzerland) 2025
  • “...SRC 45 9 P35354 PTGS2 45 10 P03372 ESR1 44 11 P07900 HSP90AA1 43 12 P37231 PPARG 42 13 P49841 GSK3B 38 14 P05362 ICAM1 36 15 P09601 HMOX1 36 16 P08238 HSP90AB1 36 17 P35968 KDR 35 18 Q04206 RELA 34 19 P42224 STAT1 34...”
• The Potential of Siraitia grosvenorii to Promote Bone Regeneration via Modulating Macrophage Polarization: A Network Pharmacology and Experimental Study
  Mai, International journal of molecular sciences 2025
• The ultrafine powder of atractylodis macrocephalae rhizoma improves immune function in naturally aging rats by regulating the PI3K/Akt/NF-κB signaling pathway
  Yu, Frontiers in pharmacology 2025 (no snippet)
• Uncovering mechanism of hepatotoxicity diseases caused by tetrahydrocannabinol based on novel network toxicology and experimental verification.
  Zou, Scientific reports 2025
• Neuroprotective thiazole sulfonamides against 6-OHDA-induced Parkinsonian model: in vitro biological and in silico pharmacokinetic assessments.
  Ruankham, RSC advances 2025
  • “...deacetylase sirtuin-1 SIRT1 Cell cycle, DNA regulation, metabolism, apoptosis, and autophagy 4 101.67 0.03 57 P37231 Peroxisome proliferator-activated receptor gamma PPARG Redox balance, immune response, and mitochondrial function 4 453.33 0.03 70 Conclusions The synergistic neuroprotective efficiency of twelve thiazole sulfonamides against 6-OHDA-induced Parkinsonian characteristics was...”
• Variant effect predictor correlation with functional assays is reflective of clinical classification performance.
  Livesey, Genome biology 2025
• More

NP_001272587 peroxisome proliferator-activated receptor gamma from Capra hircus
62% identity, 15% coverage

• SCD1 Alters Long-Chain Fatty Acid (LCFA) Composition and Its Expression Is Directly Regulated by SREBP-1 and PPARγ 1 in Dairy Goat Mammary Cells.
  Yao, Journal of cellular physiology 2017 (PubMed)
  • GeneRIF: SCD1 could markedly affect the fatty acid composition and rate of triacylglycerol synthesis through direct regulation via SREBP-1 and PPARG1.
• Expression patterns of peroxisome proliferator-activated receptor gamma 1 versus gamma 2, and their association with intramuscular fat in goat tissues.
  Li, Gene 2013 (PubMed)
  • GeneRIF: PPARgamma1 is rather active for most tissues of goat, and closely related with the muscular fat metabolism during early postnatal life.

3dzuA / P19793 Intact ppar gamma - rxr alpha nuclear receptor complex on DNA bound with bvt.13, 9-cis retinoic acid and ncoa2 peptide (see paper)
57% identity, 26% coverage

• Ligands: dna; peptide; zinc ion; (9cis)-retinoic acid (3dzuA)

NHR23_CAEEL / P41828 Nuclear hormone receptor family member nhr-23; Steroid hormone receptor family member chr-3 from Caenorhabditis elegans (see 5 papers)
64% identity, 12% coverage

• function: Orphan nuclear receptor. Transcription factor (PubMed:11416209, PubMed:21910973, PubMed:35968765, PubMed:9521900). Modulates expression of target genes, such as Period protein homolog lin-42 and microRNA let-7, by binding to hormone response elements (HRE) (PubMed:35968765, PubMed:9521900). Involved in promoting oscillatory expression of the primary transcripts of let-7 and paralogous microRNAs miR-48, miR-84, and miR-241 (PubMed:35968765). Plays a role in normal development and required to regulate each larval molt (PubMed:11416209, PubMed:21910973, PubMed:9521900). Involved in regulating both the frequency and number of molts, acting as part of a negative feedback loop with the let-7 family of microRNAs, perhaps contributing to a self-sustaining molecular-genetic oscillator (PubMed:35968765). Positively modulates expression of collagen and hedgehog-related genes (PubMed:11416209, PubMed:21910973). Involved in development of the gonad and associated epidermal structures (PubMed:11416209, PubMed:9521900). Required in spermatogenesis, acting following the sperm/oocyte cell fate decision, downstream of the canonical sex-determination pathway (PubMed:33060131). Involved in regulating formation of the sperm-specific fibrous body-membranous organelle (FB-MO) complexes, acting independently of transcription regulator spe-44 (PubMed:33060131).
  disruption phenotype: RNAi-mediated knockdown in the adult causes abnormally small larval progeny, difficulties in shedding old cuticles after molts and larval arrest at the L3 or L4 stage (PubMed:9521900). Up to three previous cuticle segments may remain attached near the tail (PubMed:9521900). Less than 1% of affected larvae survive to adulthood and in all cases have a strong Dumpy (short and fat) phenotype (PubMed:9521900). Defects in gonad morphogenesis and seam cell (lateral epidermis) development (PubMed:9521900). Knockdown in L1 larvae causes the majority of affected individuals to have defects in the L3/L4 molt (PubMed:11416209, PubMed:35968765). Reduces the peak level of expression of fbn-1 by 2-fold during both L3 and L4 stages (PubMed:35968765). Knockdown in L2 larvae results in a molting defect mainly at the L4/adult (A) transition (PubMed:11416209). Knockdown in L3 larvae causes developmental arrest and a molting defect in the L4/A molt (PubMed:11416209). Larval molting cycles are extended; this effect is partially suppressed in a microRNA let-7 mutant background (PubMed:35968765). Those hermaphrodite adults which survive knockdown at larval stages show defects in gonad development, with gonad often appearing misshapen, folded and constricted (PubMed:11416209). Males which survive knockdown often have tail morphogenesis defects, in addition to molting defects (PubMed:11416209). Significantly (5-11 fold) reduces level of expression of cuticle collagen dpy-7 (PubMed:11416209). Germline-targeted knockdown in hermaphrodites or males causes sterility (PubMed:33060131). Primary spermatocytes arrest in a metaphase I-like state (PubMed:33060131). Spermatocytes have defects in both cytokinesis and post-meiotic partitioning (PubMed:33060131).
• The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: implications for developing new model organisms
  Kaur, PloS one 2015
  • “...BgNR1D3 + * 201 1E E78 AAR30507 E78 AAF51692 BgE78 534 LgE78 163301 1F HR23 P41828 HR3 AAA28461 BgHR3 73 LgHR3 167096 ROR AAH08831 BgROR 74 LgROR 155536 ROR AAH93774 ROR AAA64751 1G HR14 AAA96982 1H EcR NP724456 BgEcR 1481 LgEcR 170342 LXR AAV38218 LXR NP_009052...”

NP_001032969 Nuclear hormone receptor family member nhr-23 from Caenorhabditis elegans
64% identity, 17% coverage

• Ror homolog nhr-23 is essential for both developmental clock and circadian clock in C. elegans.
  Hiroki, Communications biology 2024
  • GeneRIF: Ror homolog nhr-23 is essential for both developmental clock and circadian clock in C. elegans.
• NHR-23 activity is necessary for C. elegans developmental progression and apical extracellular matrix structure and function.
  Johnson, Development (Cambridge, England) 2023
  • GeneRIF: NHR-23 activity is necessary for C. elegans developmental progression and apical extracellular matrix structure and function.
• The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator of C. elegans spermatogenesis.
  Ragle, Development (Cambridge, England) 2020
  • GeneRIF: The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator of C. elegans spermatogenesis.
• NHR-23 dependent collagen and hedgehog-related genes required for molting.
  Kouns, Biochemical and biophysical research communications 2011
  • GeneRIF: these results indicate that NHR-23 is a critical co-regulator of functionally linked genes involved in growth and molting and reveal evolutionary parallels among the ecdysozoa.
• The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25.
  Hayes, Development (Cambridge, England) 2006 (PubMed)
  • GeneRIF: mir-84 and let-7 promote exit from the molting cycle by regulating targets in the heterochronic pathway and also nhr-23 and nhr-25, genes encoding conserved nuclear hormone receptors essential for larval molting.

7UP2_DROME / P16376 Steroid receptor seven-up, isoform A; Nuclear receptor subfamily 2 group F member 3, isoform A from Drosophila melanogaster (Fruit fly) (see 2 papers)
56% identity, 10% coverage

• function: Receptor that is required in photoreceptors R1, R3, R4 and R6 during eye development; generation of the ganglion mother cell-2 (GMC- 2) fate in the nb7-3 lineage, coinciding with the transition in the expression of HB to KR in the neuroblasts (NBs).

NP_001163024 hormone receptor-like in 38, isoform D from Drosophila melanogaster
59% identity, 9% coverage

• Mef2 induction of the immediate early gene Hr38/Nr4a is terminated by Sirt1 to promote ethanol tolerance.
  Adhikari, Genes, brain, and behavior 2019
  • GeneRIF: Loss of Hr38 decreases ethanol tolerance and causes ethanol preference. Hr38 functions as an immediate early transcription factor that promotes ethanol behavioral plasticity.
• Immediate-Early Promoter-Driven Transgenic Reporter System for Neuroethological Research in a Hemimetabolous Insect
  Watanabe, eNeuro 2018
  • “...above the alignment. GenBank IDs of proteins are following: D. melanogaster DHR38 isoform D (DHR38-D), NP_001163024; Bombyx mori HR38, P49870.1; Tribolium castaneum HR38, XP_008194320.1; Apis mellifera HR38, XP_016773251.1; Zootermopsis nevadensis HR38, KDR09534.1. B , C , Expression of Gryllus hr38 after PTX injection in the brains...”
• Visualization of neural activity in insect brains using a conserved immediate early gene, Hr38.
  Fujita, Current biology : CB 2013 (PubMed)
  • GeneRIF: Hr38 was identified as a novel immediate early gene that is transiently expressed in the male silkmoth Bombyx mori by female odor stimulation. Hr38 was also used as a neural activity marker in the fly Drosophila melanogaster.
• The composite nature of the interaction between nuclear receptors EcR and DHR38.
  Zoglowek, Biological chemistry 2012 (PubMed)
  • GeneRIF: DHR38 might modulate the activity of the Usp-EcR heterodimer by forming complexes with both of its components
• Intrinsic disorder of Drosophila melanogaster hormone receptor 38 N-terminal domain.
  Dziedzic-Letka, Proteins 2011 (PubMed)
  • GeneRIF: dHR38-N-Terminal domain exhibits a characteristic reminiscent of pre-molten globule-like intrinsically disordered proteins
• The Drosophila NR4A nuclear receptor DHR38 regulates carbohydrate metabolism and glycogen storage.
  Ruaud, Molecular endocrinology (Baltimore, Md.) 2011
  • GeneRIF: Nutritional regulation of DHR38 expression maintains the proper uptake and storage of glycogen during the growing larval stage of development.
• Drosophila DHR38 nuclear receptor is required for adult cuticle integrity at eclosion.
  Kozlova, Developmental dynamics : an official publication of the American Association of Anatomists 2009
  • GeneRIF: DHR38(Y214) mutants display minor effects on ecdysone-regulated transcription at the onset of metamorphosis
• The orphan nuclear receptor DHR38 influences transcription of the DOPA decarboxylase gene in epidermal and neural tissues of Drosophila melanogaster.
  Davis, Genome 2007 (PubMed)
  • GeneRIF: DHR38 may act as a positive regulator of neural Ddc expression
• More

XP_008258423 peroxisome proliferator-activated receptor gamma isoform X1 from Oryctolagus cuniculus
62% identity, 15% coverage

• Rosuvastatin relieves myocardial ischemia/reperfusion injury by upregulating PPAR‑γ and UCP2.
  Wang, Molecular medicine reports 2018
  • GeneRIF: the present study demonstrated that RS protects primary myocardial cells against OGD/R injury by regulating PPARgamma and UCP2. RS may be a promising therapeutic agent for treatment of myocardial ischemia/reperfusion injury.
• Effects of vitamin E on peroxisome proliferator-activated receptor γ and nuclear factor-erythroid 2-related factor 2 in hypercholesterolemia-induced atherosclerosis.
  Bozaykut, Free radical biology & medicine 2014 (PubMed)
  • GeneRIF: vitamin E supplementation affords protection by decreasing MMP-1 and increasing PPARg, GSTa, and ABCA1 levels in aortae of rabbits fed a cholesterol-rich diet
• Evidence for a luteotropic role of peroxisome proliferator-activated receptor gamma: expression and in vitro effects on enzymatic and hormonal activities in corpora lutea of pseudopregnant rabbits.
  Zerani, Biology of reproduction 2013 (PubMed)
  • GeneRIF: PPARgamma plays a luteotropic role in pseudopregnant rabbits, through PTGS2 down-regulation and 3beta-HSD up-regulation, with a consequent PGF2alpha decrease and progesterone increase.
• Telmisartan protects against microvascular dysfunction during myocardial ischemia/reperfusion injury by activation of peroxisome proliferator-activated receptor γ.
  Zeng, BMC cardiovascular disorders 2013
  • GeneRIF: Telmisartan improves microvascular dysfunction during myocardial ischemia/reperfusion injury via the PPARgamma pathway.
• Up-regulating PPAR-γ expression and NO concentration, and down-regulating PAI-1 concentration in a rabbit atherosclerotic model: the possible antiatherogenic and antithrombotic effects of atorvastatin.
  Yang, International journal of cardiology 2010 (PubMed)
  • GeneRIF: In an animal model of atherosclerosis, the expression of PPAR-gamma is upregulated following atorvastatin administration.
• Antidiabetic drug pioglitazone protects the heart via activation of PPAR-gamma receptors, PI3-kinase, Akt, and eNOS pathway in a rabbit model of myocardial infarction.
  Yasuda, American journal of physiology. Heart and circulatory physiology 2009 (PubMed)
  • GeneRIF: Antidiabetic drug pioglitazone protects the heart via activation of PPAR-gamma receptors, PI3-kinase, Akt, and eNOS pathway in a rabbit model of myocardial infarction.
• [Effects of Tongxinluo on MMP-3, 9 and PPARgamma expressions in atherosclerotic rabbits].
  Cao, Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2009 (PubMed)
  • GeneRIF: Tongxinluo can inhibit the expression of MMP-3 and 9 and increase the expression of PPARgamma in atherosclerotic rabbits.
• Effect of niacin on adipocyte leptin in hypercholesterolemic rabbits.
  Yang, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology (PubMed)
  • GeneRIF: Niacin Reduces serum level and adipose mRNA expression of leptin and up-regulates PPARgamma and CD36 mRNA expression in hypercholesterolemic rabbits.
• More

XP_005669845 peroxisome proliferator-activated receptor gamma isoform X1 from Sus scrofa
62% identity, 15% coverage

• The importance of the nuclear positioning of the PPARG gene for its expression during porcine in vitro adipogenesis.
  Stachecka, Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 2019
  • GeneRIF: functionally distinct alleles of the PPARG gene are positioned in different parts of the cell nucleus. This confirms the importance of nuclear architecture to the regulation of PPARG gene transcription, and thus to the fate of the adipose cell.
• Overexpression of DNMT3A promotes proliferation and inhibits differentiation of porcine intramuscular preadipocytes by methylating p21 and PPARg promoters.
  Qimuge, Gene 2019 (PubMed)
  • GeneRIF: Study demonstrated that overexpression of DNMT3A promoted the expression of cell proliferation markers but significantly decreased the expression of p21 to repress cell proliferation by the methylation of p21 promoter. Moreover, overexpression of DNMT3A decreased lipid accumulation and significantly down-regulated the levels of adipogenic marker genes through the methylation of PPARg promoter.
• Dietary protein-induced hepatic IGF-1 secretion mediated by PPARγ activation.
  Wan, PloS one 2017
  • GeneRIF: The immunoprecipitation results also showed that high AA concentrations significantly increased the interaction of mTOR and PPARg. In summary, PPARg plays an important role in the regulation of IGF-1 secretion and gene expression in response to dietary protein.
• Peroxisome proliferator‑activated receptor γ mediates porcine placental angiogenesis through hypoxia inducible factor‑, vascular endothelial growth factor‑ and angiopoietin‑mediated signaling.
  Zhang, Molecular medicine reports 2017
  • GeneRIF: The results of the present study suggested that PPARG may mediate porcine placental angiogenesis, by interfering with hypoxia inducible factor, vascular endothelial growth factor and angiopoietinmediated signaling.
• miR-130a regulates differential lipid accumulation between intramuscular and subcutaneous adipose tissues of pigs via suppressing PPARG expression.
  Wei, Gene 2017 (PubMed)
  • GeneRIF: The results suggest the higher expression of miR-130a, which targeting peroxisome proliferator-activated receptor gamma, may be the reason for less fat deposition in intramuscular adipose tissue than subcutaneous adipose tissue.
• Expression of peroxisome proliferator-activated receptors is regulated by gonadotropins and steroid hormones in in vitro porcine ovarian follicles.
  Kurowska, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2017 (PubMed)
  • GeneRIF: Our results provide novel insights into regulation of PPAR expression in ovarian follicles. We observed that FSH increased mRNA and protein expression of all PPARs isoforms, while LH only increased PPAR alpha and gamma. Steroids like progesterone and estradiol increased expression of PPAR alpha and gamma without affecting the beta isoform, while testosterone had no effect on all PPARs expression.
• In vitro interaction between resistin and peroxisome proliferator-activated receptor γ in porcine ovarian follicles.
  Rak-Mardyła, Reproduction, fertility, and development 2016 (PubMed)
  • GeneRIF: The data suggest that there is local cooperation between resistin and PPARgamma expression in the porcine ovary. Resistin significantly increased the expression of PPARgamma, whereas PPARgamma decreased resistin expression; thus, PPARgamma is a new key regulator of resistin expression and function.
• MyoD promotes porcine PPARγ gene expression through an E-box and a MyoD-binding site in the PPARγ promoter region.
  Deng, Cell and tissue research 2016 (PubMed)
  • GeneRIF: an Enhancer box and a binding site for a cooperative co-activator of MyoD are present in the promoter region of porcine PPARgamma.
• More

D2KUA6 Peroxisome proliferator-activated receptor gamma from Homo sapiens
62% identity, 15% coverage

• β'-COP mediated loading of PPARγ into trophoblast-derived extracellular vesicles
  Luo, Cellular and molecular life sciences : CMLS 2024
  • “...derived EVs Accession Description Score Coverage Proteins Unique Peptides Peptides PSMs AAs MW [kDa] calc.pl D2KUA6 HUMAN Peroxisome proliferator-activated receptor gamma OS=Homo sapiens OX=9606 GN=PPARG PE=2 SV=1 51.93 54.92 1 1 15 37 1906 305.4 8.27 Q53EW1 HUMAN Peroxisome proliferator-activated receptor gamma (Fragment) OS=Homo sapiens OX=9606...”
  • “...derived EVs Accession Description Score Coverage Proteins Unique Peptides Peptides PSMs AAs MW [kDa] calc.pl D2KUA6 HUMAN Peroxisome proliferator-activated receptor gamma OS=Homo sapiens OX=9606 GN=PPARG PE=2 SV=1 60.83 40.53 1 1 23 35 1816 335.1 5.22 Q53EW1 HUMAN Peroxisome proliferator-activated receptor gamma (Fragment) OS=Homo sapiens OX=9606...”
• The Differences in the Proteome Profile of Cannabidiol-Treated Skin Fibroblasts following UVA or UVB Irradiation in 2D and 3D Cell Cultures
  Gęgotek, Cells 2019
  • “...5.2 Q9UBK2 Peroxisome proliferator-activated receptor gamma coactivator 1A (PPARGC1A) intracellular signaling, antioxidant response 2.6 4.9 D2KUA6 NR1C3 (PPAR subunit) intracellular signaling, antioxidant response 4.9 3.9 Q3C1U4 PPAR-DNA-binding domain-interacting protein 1 (PDIP1) intracellular signaling, antioxidant response 3.3 3.1 P35669 -Glutamate cysteine ligase A1 (-GCS A1) catalytic activity,...”

Q53EW1 Peroxisome proliferator-activated receptor gamma (Fragment) from Homo sapiens
62% identity, 15% coverage

• β'-COP mediated loading of PPARγ into trophoblast-derived extracellular vesicles
  Luo, Cellular and molecular life sciences : CMLS 2024
  • “...OS=Homo sapiens OX=9606 GN=PPARG PE=2 SV=1 51.93 54.92 1 1 15 37 1906 305.4 8.27 Q53EW1 HUMAN Peroxisome proliferator-activated receptor gamma (Fragment) OS=Homo sapiens OX=9606 GN=PPARG PE=2 SV=1 67.88 35.89 1 1 23 15 1530 226.5 6.91 E9PFV2 HUMAN Peroxisome proliferator-activated receptor gamma OS=Homo sapiens OX=9606...”
  • “...OS=Homo sapiens OX=9606 GN=PPARG PE=2 SV=1 60.83 40.53 1 1 23 35 1816 335.1 5.22 Q53EW1 HUMAN Peroxisome proliferator-activated receptor gamma (Fragment) OS=Homo sapiens OX=9606 GN=PPARG PE=2 SV=1 48.43 59.32 1 1 14 25 2560 204.5 3.41 E9PFV2 HUMAN Peroxisome proliferator-activated receptor gamma OS=Homo sapiens OX=9606...”

XP_014985686 peroxisome proliferator-activated receptor gamma isoform X2 from Macaca mulatta
62% identity, 15% coverage

• Expression of peroxisome proliferator-activated receptor-gamma in the substantia nigra of hemiparkinsonian nonhuman primates.
  Swanson, Neurological research 2014
  • GeneRIF: study found PPAR-gamma expression was prominent in the subthalamic nucleus, oculomotor nucleus, ventral tegmental nucleus, and to a lesser extent, in the putamen; 3 or 12 months after MPTP, only the lesioned putamen had increased PPAR-gamma
• Effects of aleglitazar, a balanced dual peroxisome proliferator-activated receptor α/γ agonist on glycemic and lipid parameters in a primate model of the metabolic syndrome.
  Hansen, Cardiovascular diabetology 2011
  • GeneRIF: Aleglitazar, a dual PPARalpha/gamma agonist, has beneficial effects on both lipid and glucose parameters in a primate model of the metabolic syndrome.

NHR6_CAEEL / P41829 Nuclear hormone receptor family member nhr-6; Nuclear receptor subfamily 4 group A member 5; Steroid hormone receptor family member cnr8 from Caenorhabditis elegans (see 4 papers)
NP_497731 Nuclear hormone receptor family member nhr-6 from Caenorhabditis elegans
60% identity, 12% coverage

• function: Transcriptional activator that induces gene expression by binding to the NGFI-B response element (NBRE) 5'-AAAGGTCA-3' (PubMed:20506374). Required for proper morphogenesis of the spermatheca and the spermatheca-uterine valve formation (PubMed:18096150, PubMed:25529479). Promotes cell proliferation and differentiation of the spermatheca precursor cells during spermatheca development in larval stage L4 (PubMed:18096150, PubMed:25529479). Might play a role in promoting G1/S phase progression in the spermatheca precursor cell lineage (PubMed:25529479). Also required for the differentiation of the spermatheca-uterine junction core (sujc) cells which are generating the spermatheca-uterine valve (PubMed:18096150).
  disruption phenotype: Reduced brood size, abnormal egg morphology and arrested egg development. Defects in ovulation with fragmentation of the proximal oocyte and endomitosis. Misplacement of ovulated oocytes into the gonad arms due to a lack of spermatheca-uterine valve formation. Degeneration of gonad tissue. Decreased spermatheca organ size due to decreased spermatheca cell number. Disorganized actin microfilaments in the spermatheca, lack of distal constriction and defects in spermathecal cell differentiation. Misexpression of let-502 in all cells of the spermatheca instead of restricted expression to the distal and proximal regions of the spermatheca. Abnormal differentiation and morphology of the sujc cells that form the core of the spermatheca-uterine valve (PubMed:18096150). Lack of cell divisions of the proximal spermatheca precursor daughter cells due to a failure of progressing to S phase during larval stage L4 (PubMed:25529479). In a fzr-1(ku298) mutant background, increase in spermatheca nuclei number as compared to the nhr-6 single mutant (PubMed:25529479). In a fog- 2(q71) mutant background, a large mass of fragmented oocytes in the spermatheca and uterus (PubMed:18096150). RNAi-mediated knockdown leads to reduced brood size and abnormal egg morphology (PubMed:20506374). In a vab-1(e2), vab-1(e699), vab-2(ju1) or vab-2(e96) mutant background, enhanced reduction in brood size (PubMed:25529479). In a vab-2(ju1) mutant background, reduced spermatheca cell number and abnormal spermatheca morphology (PubMed:25529479). In a RNAi-sensitive rrf- 3(pk1426) mutant background, defects in spermatheca morphology, including decreased organ size, decreased spermatheca cell number and misplaced spermatheca nuclei. In a RNAi-sensitive eri-1(mg366) mutant background, reduced brood size, abnormal egg morphology and arrested eggs (PubMed:18096150).
• The C. elegans NR4A nuclear receptor gene nhr-6 promotes cell cycle progression in the spermatheca lineage.
  Praslicka, Developmental dynamics : an official publication of the American Association of Anatomists 2015
  • GeneRIF: Genetic suppression of the proliferation phenotype does not affect the differentiation phenotypes observed in nhr-6 mutants, indicating a dualistic role for nhr-6 in regulating cell proliferation and cell differentiation during spermatheca organogenesis.
• C. elegans nuclear receptor NHR-6 functionally interacts with the jun-1 transcription factor during spermatheca development.
  Gissendanner, Genesis (New York, N.Y. : 2000) 2014
  • GeneRIF: Results show that nhr-6 and jun-1 function together to regulate development of the spermatheca and are necessary for generating an organ with the normal number of cells.
• A functional NR4A nuclear receptor DNA-binding domain is required for organ development in Caenorhabditis elegans.
  Heard, Genesis (New York, N.Y. : 2000) 2010
  • GeneRIF: Study demonstrates an in vivo requirement for NHR-6, an NR4A nuclear receptor ortholog, DNA-binding domain in a whole organism.

XP_021325424 hepatocyte nuclear factor 4-alpha isoform X2 from Danio rerio
55% identity, 16% coverage

• Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor Hepatocyte nuclear factor 4 alpha.
  Davison, Genome research 2017
  • GeneRIF: These results indicate a critical and conserved role for HNF4A in maintaining intestinal homeostasis in response to microbiota.

NP_001246824 ftz transcription factor 1, isoform C from Drosophila melanogaster
59% identity, 9% coverage

• Domain analysis of Drosophila Blimp-1 reveals the importance of its repression function and instability in determining pupation timing.
  Sarhan, Genes to cells : devoted to molecular & cellular mechanisms 2023 (PubMed)
  • GeneRIF: Domain analysis of Drosophila Blimp-1 reveals the importance of its repression function and instability in determining pupation timing.
• MLE Helicase Is a New Participant in the Transcription Regulation of the ftz-f1 Gene Encoding Nuclear Receptor in Higher Eukaryotes.
  Nikolenko, Doklady. Biochemistry and biophysics 2021 (PubMed)
  • GeneRIF: MLE Helicase Is a New Participant in the Transcription Regulation of the ftz-f1 Gene Encoding Nuclear Receptor in Higher Eukaryotes.
• Orphan nuclear receptor ftz-f1 (NR5A3) promotes egg chamber survival in the Drosophila ovary.
  Beachum, G3 (Bethesda, Md.) 2021
  • GeneRIF: Orphan nuclear receptor ftz-f1 (NR5A3) promotes egg chamber survival in the Drosophila ovary.
• Nuclear receptor Ftz-f1 promotes follicle maturation and ovulation partly via bHLH/PAS transcription factor Sim.
  Knapp, eLife 2020
  • GeneRIF: Nuclear receptor Ftz-f1 promotes follicle maturation and ovulation partly via bHLH/PAS transcription factor Sim.
• The intrinsically disordered region of GCE protein adopts a more fixed structure by interacting with the LBD of the nuclear receptor FTZ-F1.
  Kolonko, Cell communication and signaling : CCS 2020
  • GeneRIF: The intrinsically disordered region of GCE protein adopts a more fixed structure by interacting with the LBD of the nuclear receptor FTZ-F1.
• dTcf/Pangolin suppresses growth and tumor formation in Drosophila.
  Song, Proceedings of the National Academy of Sciences of the United States of America 2019
  • GeneRIF: We identify the conserved transcription factors Sox box protein 15 (Sox15) and Ftz transcription factor 1 (Ftz-f1) as genes controlled by dTcf/Pan involved in tumor development. In conclusion, this study reports a role for dTcf/Pan as a repressor of normal and oncogenic growth and identifies the genes inducing tumorigenesis downstream of dTcf/Pan.
• Solution Nuclear Magnetic Resonance Studies of the Ligand-Binding Domain of an Orphan Nuclear Receptor Reveal a Dynamic Helix in the Ligand-Binding Pocket.
  Daffern, Biochemistry 2018
  • GeneRIF: the alpha6 helix is dynamic in solution when Ftz-F1 is bound to the LxxLL motif of its cofactor Ftz, undergoing motions on the fast (picosecond to nanosecond) as well as slow (microsecond to millisecond) time scales.
• Studying a novel ecdysone-dependent enhancer.
  Nikolenko, Doklady. Biochemistry and biophysics 2017 (PubMed)
  • GeneRIF: a novel ecdysone-dependent enhancer in the intron of ftz-f1 gene
• More

NR5A2_HUMAN / O00482 Nuclear receptor subfamily 5 group A member 2; Alpha-1-fetoprotein transcription factor; B1-binding factor; hB1F; CYP7A promoter-binding factor; Hepatocytic transcription factor; Liver receptor homolog 1; LRH-1 from Homo sapiens (Human) (see 25 papers)
NP_995582 nuclear receptor subfamily 5 group A member 2 isoform 1 from Homo sapiens
XP_001142695 nuclear receptor subfamily 5 group A member 2 isoform X1 from Pan troglodytes
59% identity, 14% coverage

• function: Orphan nuclear receptor that binds DNA as a monomer to the 5'-TCAAGGCCA-3' sequence and controls expression of target genes: regulates key biological processes, such as early embryonic development, cholesterol and bile acid synthesis pathways, as well as liver and pancreas morphogenesis (PubMed:16289203, PubMed:18410128, PubMed:21614002, PubMed:32433991, PubMed:38409506, PubMed:9786908). Ligand-binding causes conformational change which causes recruitment of coactivators, promoting target gene activation (PubMed:21614002). The specific ligand is unknown, but specific phospholipids, such as phosphatidylethanolamine, phosphatidylserine, dilauroyl phosphatidylcholine and diundecanoyl phosphatidylcholine can act as ligand in vitro (PubMed:15707893, PubMed:15723037, PubMed:15897460, PubMed:21614002, PubMed:22504882, PubMed:23737522, PubMed:26416531, PubMed:26553876). Acts as a pioneer transcription factor, which unwraps target DNA from histones and elicits local opening of closed chromatin (PubMed:38409506). Plays a central role during preimplantation stages of embryonic development (By similarity). Plays a minor role in zygotic genome activation (ZGA) by regulating a small set of two-cell stage genes (By similarity). Plays a major role in morula development (2-16 cells embryos) by acting as a master regulator at the 8-cell stage, controlling expression of lineage-specifying transcription factors and genes involved in mitosis, telomere maintenance and DNA repair (By similarity). Zygotic NR5A2 binds to both closed and open chromatin with other transcription factors, often at SINE B1/Alu repeats DNA elements, promoting chromatin accessibility at nearby regulatory regions (By similarity). Also involved in the epiblast stage of development and embryonic stem cell pluripotency, by promoting expression of POU5F1/OCT4 (PubMed:27984042). Regulates other processes later in development, such as formation of connective tissue in lower jaw and middle ear, neural stem cell differentiation, ovarian follicle development and Sertoli cell differentiation (By similarity). Involved in exocrine pancreas development and acinar cell differentiation (By similarity). Acts as an essential transcriptional regulator of lipid metabolism (PubMed:20159957). Key regulator of cholesterol 7-alpha- hydroxylase gene (CYP7A) expression in liver (PubMed:10359768). Also acts as a negative regulator of inflammation in different organs, such as, liver and pancreas (PubMed:20159957). Protects against intestinal inflammation via its ability to regulate glucocorticoid production (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (PubMed:20159957). Acts as a regulator of immunity by promoting lymphocyte T-cell development, proliferation and effector functions (By similarity). Also involved in resolution of endoplasmic reticulum stress in the liver (By similarity).
  function: [Isoform 3]: In constrast to isoform 1 and isoform 2, does not induce cholesterol 7-alpha-hydroxylase gene (CYP7A) promoter activity.
  function: (Microbial infection) Plays a crucial role for hepatitis B virus gene transcription and DNA replication. Mechanistically, synergistically cooperates with HNF1A to up-regulate the activity of one of the critical cis-elements in the hepatitis B virus genome enhancer II (ENII).
  subunit: Monomer; Binds DNA as a monomer (PubMed:16289203, PubMed:38409506). Interacts with nuclear receptor corepressors NR0B1 and NR0B2; repressing NR5A2 nuclear receptor activity (PubMed:15723037, PubMed:22504882, PubMed:26416531, PubMed:32433991). Interacts with nuclear receptor coactivators CTNNB1, PPARGC1A and NCOA2; interaction takes place following ligand-binding and promotes target gene activation (PubMed:15707893, PubMed:15897460, PubMed:22187462, PubMed:22504882, PubMed:26553876, PubMed:27694446, PubMed:28363985, PubMed:31419141, PubMed:32433991, PubMed:32631515, PubMed:33335203, PubMed:35503419). Interacts (when sumoylated) with GPS2; interaction with GPS2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (PubMed:20159957). Interacts with HNF1A (PubMed:14728801). Interacts with GRIP1 (By similarity).
• New High-Throughput Screen Discovers Novel Ligands of Full-Length Nuclear Receptor LRH-1.
  Malabanan, ACS chemical biology 2023
  • “...wild type human LRH-1 ( NR5A2 ) ligand-binding domain (LBD) construct (residues 266541, UniProt ID O00482) and Cys-lite mutants (C311/346S), (C311/487S) and (C346/487S) were cloned into isopropyl 1-thio-b-galactopyranoside (IPTG)-inducible pET vector with an N-terminal His-tag and expressed in E. coli BL21 dE3 using standard methods, briefly...”
• Targeting Nuclear Receptors in Lung Cancer-Novel Therapeutic Prospects
  Gangwar, Pharmaceuticals (Basel, Switzerland) 2022
  • “...ID: P51116), ( I ) PXR (Uniprot ID: O75469), ( J ) LRH1 (Uniprot ID: O00482), ( K ) GR (Uniprot ID: P04150), ( L ) PR (Uniprot ID: P06401), ( M ) TR (Uniprot ID: P10827). The primary structures of these proteins were downloaded from...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2021
  • “...1 Liver receptor homolog1 Systematic nomenclature NR5A1 NR5A2 HGNC, UniProt NR5A1 , Q13285 NR5A2 , O00482 Comments Reported to be inhibited by AC45594 [ 30 ] and SID7969543 [ 88 ]. 6A. Germ cell nuclear factor receptors Overview Germ cell nuclear factor receptors ( nomenclature as...”
• Integrated Structural Modeling of Full-Length LRH-1 Reveals Inter-domain Interactions Contribute to Receptor Structure and Function
  Seacrist, Structure (London, England : 1993) 2020
  • “...Protein Expression and Purification: Full-length wildtype and mutant versions of human LRH-1 (aa 1541, UniprotKB O00482) were expressed via pRSF2 vector and were carried out similar to previous studies ( Suzawa et al. , 2015 ). Briefly, BL21 dE3 E. coli was transformed with pRSF2 full-length...”
  • “...10K filter and flash frozen for storage at 80 C. LRH-1 LBD (aa 266541, UniprotKB O00482) was expressed from arabinose-inducible vector with an N-terminal His-TEV tag purchased from VectorBuilder. Briefly, BL21 AI E. coli was transformed with His-TEVLBD vector, grown at 37 C until OD 600...”
• Structural analysis of SARS-CoV-2 genome and predictions of the human interactome.
  Vandelli, Nucleic acids research 2020
  • “...library; Fisher's exact test), including Nuclear receptor subfamily 5 group A member 2 NR5A2 (DNA-binding; O00482), Interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2 (P19525), and SRSF protein kinase 1 SRPK1 (Q96SB4) as well as Influenza A ( P -value = 0.03; two hits out of four; Fisher's...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Nuclear hormone receptors
  Alexander, British journal of pharmacology 2017
  • “...1 Liver receptor homolog1 Systematic nomenclature NR5A1 NR5A2 HGNC, UniProt NR5A1 , Q13285 NR5A2 , O00482 Comments Reported to be inhibited by AC45594 [ 32 ] and SID7969543 [ 90 ]. Further reading on 5A. Fushi tarazu F1like receptors Benoit G et al. (2006) International Union...”
• Late-onset X-linked adrenal hypoplasia (DAX-1, NR0B1): two new adult-onset cases from a single center.
  Kyriakakis, Pituitary 2017
  • “...( cyan ). The comparative modelling of the human DAX-1: LHR-1 (Uniprot codes P51483 and O00482) complex was performed using the MODELLER program [ 7 ], as implemented in the Build Homology Model module of Discovery Studio v2.1 software (Accelrys Inc., San Diego, USA). The crystal...”
• Targeted proteomic approach in prostatic tissue: a panel of potential biomarkers for cancer detection
  Aiello, Oncoscience 2016
  • “...different nuclear receptors and mediated by STAT3 STAT5A STAT5B and STAT6 transcription factors 292 92. O00482 NR5A2 Nuclear receptor subfamily 5 group A member 2 * 808 61331 nucleus transcription regulation 237 93. Q5VST9 OBSCN Obscurin * 569 868484 cytoplasm involved in miofibrillogenesis 225 94. Q9C0B5...”
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• Lineage regulators TFAP2C and NR5A2 function as bipotency activators in totipotent embryos.
  Li, Nature structural & molecular biology 2024 (PubMed)
  • GeneRIF: Lineage regulators TFAP2C and NR5A2 function as bipotency activators in totipotent embryos.
• Nucleosome-bound NR5A2 structure reveals pioneer factor mechanism by DNA minor groove anchor competition.
  Kobayashi, Nature structural & molecular biology 2024
  • GeneRIF: Nucleosome-bound NR5A2 structure reveals pioneer factor mechanism by DNA minor groove anchor competition.
• Nuclear receptor 5A2 regulation of Agrp underlies olanzapine-induced hyperphagia.
  Zapata, Molecular psychiatry 2023
  • GeneRIF: Nuclear receptor 5A2 regulation of Agrp underlies olanzapine-induced hyperphagia.
• Aberrant phosphorylation of human LRH1 at serine 510 is predictable of hepatocellular carcinoma recurrence.
  Nishimagi, Clinical and experimental medicine 2023
  • GeneRIF: Aberrant phosphorylation of human LRH1 at serine 510 is predictable of hepatocellular carcinoma recurrence.
• LRH-1/NR5A2 interacts with the glucocorticoid receptor to regulate glucocorticoid resistance.
  Michalek, EMBO reports 2022
  • GeneRIF: LRH-1/NR5A2 interacts with the glucocorticoid receptor to regulate glucocorticoid resistance.
• MicroRNA-433-3p enhances chemosensitivity of glioma to cisplatin by downregulating NR5A2.
  Li, Brain and behavior 2022
  • GeneRIF: MicroRNA-433-3p enhances chemosensitivity of glioma to cisplatin by downregulating NR5A2.
• Nuclear-mitochondrial crosstalk: On the role of the nuclear receptor liver receptor homolog-1 (NR5A2) in the regulation of mitochondrial metabolism, cell survival, and cancer.
  Michalek, IUBMB life 2021 (PubMed)
  • GeneRIF: Nuclear-mitochondrial crosstalk: On the role of the nuclear receptor liver receptor homolog-1 (NR5A2) in the regulation of mitochondrial metabolism, cell survival, and cancer.
• Epithelial Nr5a2 heterozygosity cooperates with mutant Kras in the development of pancreatic cystic lesions.
  Cobo, The Journal of pathology 2021 (PubMed)
  • GeneRIF: Epithelial Nr5a2 heterozygosity cooperates with mutant Kras in the development of pancreatic cystic lesions.
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• Integrated Structural Modeling of Full-Length LRH-1 Reveals Inter-domain Interactions Contribute to Receptor Structure and Function
  Seacrist, Structure (London, England : 1993) 2020
  • “...ClustalOmega ( Madeira et al. , 2019 ): Homo sapiens LRH-1 (O00482), Pan troglodytes LRH-1 (XP_001142695), Mus musculus LRH-1 (P45448), Rattus norvegicus LRH-1 (Q9QWM1), Bos taurus LRH-1 (NP_001193745), Equus caballus LRH-1 (XP_023488164), Sus scrofa LRH-1 (AFD98842), Danio rerio LRH-1 (AAI63522), Homo sapiens SF-1 (Q13285), Pan troglodytes...”

NP_619726 peroxisome proliferator-activated receptor gamma isoform 1 from Homo sapiens
E9PFV2 Peroxisome proliferator-activated receptor gamma from Homo sapiens
62% identity, 15% coverage

• Testicular ACE regulates sperm metabolism and fertilization through the transcription factor PPARγ.
  Shibata, The Journal of biological chemistry 2024
  • GeneRIF: Testicular ACE regulates sperm metabolism and fertilization through the transcription factor PPARgamma.
• Cutting Edge: Cytosolic Receptor AIM2 Is Induced by Peroxisome Proliferator-activated Receptor γ following Mycobacterium tuberculosis Infection of Human Macrophages but Does Not Contribute to IL-1β Release.
  Arnett, Journal of immunology (Baltimore, Md. : 1950) 2024
  • GeneRIF: Cutting Edge: Cytosolic Receptor AIM2 Is Induced by Peroxisome Proliferator-activated Receptor gamma following Mycobacterium tuberculosis Infection of Human Macrophages but Does Not Contribute to IL-1beta Release.
• Adipocyte‑rich microenvironment promotes chemoresistance via upregulation of peroxisome proliferator‑activated receptor gamma/ABCG2 in epithelial ovarian cancer.
  Chen, International journal of molecular medicine 2024
  • GeneRIF: Adipocyte-rich microenvironment promotes chemoresistance via upregulation of peroxisome proliferator-activated receptor gamma/ABCG2 in epithelial ovarian cancer.
• Association of Polymorphic Variants of TCF7L2 and PPARG Genes with Metabolic Markers in Patients with Early Disorders of Carbohydrate Metabolism.
  Isakova, Bulletin of experimental biology and medicine 2024 (PubMed)
  • GeneRIF: Association of Polymorphic Variants of TCF7L2 and PPARG Genes with Metabolic Markers in Patients with Early Disorders of Carbohydrate Metabolism.
• Identification of PPARG as key gene to link coronary atherosclerosis disease and rheumatoid arthritis via microarray data analysis.
  Zhang, PloS one 2024
  • GeneRIF: Identification of PPARG as key gene to link coronary atherosclerosis disease and rheumatoid arthritis via microarray data analysis.
• Dual function of activated PPARγ by ligands on tumor growth and immunotherapy.
  Chen, Medical oncology (Northwood, London, England) 2024 (PubMed)
  • GeneRIF: Dual function of activated PPARgamma by ligands on tumor growth and immunotherapy.
• Abscisic acid signaling through LANCL2 and PPARγ induces activation of p38MAPK resulting in dormancy of prostate cancer metastatic cells.
  Parajuli, Oncology reports 2024
  • GeneRIF: Abscisic acid signaling through LANCL2 and PPARgamma induces activation of p38MAPK resulting in dormancy of prostate cancer metastatic cells.
• Tumor necrosis factor receptor-associated factor 5 protects against intimal hyperplasia by regulation of macrophage polarization via directly targeting PPARγ.
  Cheng, Inflammation research : official journal of the European Histamine Research Society ... [et al.] 2024 (PubMed)
  • GeneRIF: Tumor necrosis factor receptor-associated factor 5 protects against intimal hyperplasia by regulation of macrophage polarization via directly targeting PPARgamma.
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• β'-COP mediated loading of PPARγ into trophoblast-derived extracellular vesicles
  Luo, Cellular and molecular life sciences : CMLS 2024
  • “...OS=Homo sapiens OX=9606 GN=PPARG PE=2 SV=1 67.88 35.89 1 1 23 15 1530 226.5 6.91 E9PFV2 HUMAN Peroxisome proliferator-activated receptor gamma OS=Homo sapiens OX=9606 GN=PPARG PE=1 SV=1 39.41 42.84 1 1 11 26 1282 309.0 6.29 A0A0S2Z 4K5 HUMAN Peroxisome proliferator-activated receptor gamma (Fragment) OS=Homo sapiens...”
  • “...OS=Homo sapiens OX=9606 GN=PPARG PE=2 SV=1 48.43 59.32 1 1 14 25 2560 204.5 3.41 E9PFV2 HUMAN Peroxisome proliferator-activated receptor gamma OS=Homo sapiens OX=9606 GN=PPARG PE=1 SV=1 48.32 48.34 1 1 21 27 3282 314.0 5.21 A0A0S2Z 4K5 HUMAN Peroxisome proliferator-activated receptor gamma (Fragment) OS=Homo sapiens...”

XP_006237071 peroxisome proliferator-activated receptor gamma isoform X1 from Rattus norvegicus
62% identity, 15% coverage

• DNMT3a-mediated methylation of PPARγ promote intervertebral disc degeneration by regulating the NF-κB pathway.
  Cheng, Journal of cellular and molecular medicine 2024
  • GeneRIF: DNMT3a-mediated methylation of PPARgamma promote intervertebral disc degeneration by regulating the NF-kappaB pathway.
• Intermittent short-duration reoxygenation relieves high-altitude pulmonary hypertension via NOX4/H2O2/PPAR-γ axis.
  Li, Clinical science (London, England : 1979) 2024
  • GeneRIF: Intermittent short-duration reoxygenation relieves high-altitude pulmonary hypertension via NOX4/H2O2/PPAR-gamma axis.
• PPARγ alleviates preeclampsia development by regulating lipid metabolism and ferroptosis.
  Lai, Communications biology 2024
  • GeneRIF: PPARgamma alleviates preeclampsia development by regulating lipid metabolism and ferroptosis.
• PPARG-mediated autophagy activation alleviates inflammation in rheumatoid arthritis.
  Geng, Journal of autoimmunity 2024 (PubMed)
  • GeneRIF: PPARG-mediated autophagy activation alleviates inflammation in rheumatoid arthritis.
• SMYD2-Methylated PPARγ Facilitates Hypoxia-Induced Pulmonary Hypertension by Activating Mitophagy.
  Li, Circulation research 2024 (PubMed)
  • GeneRIF: SMYD2-Methylated PPARgamma Facilitates Hypoxia-Induced Pulmonary Hypertension by Activating Mitophagy.
• Klotho Upregulation via PPARγ Contributes to the Induction of Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning in Rats.
  Zhang, Cellular and molecular neurobiology 2023
  • GeneRIF: Klotho Upregulation via PPARgamma Contributes to the Induction of Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning in Rats.
• PPARγ/RAD21 alleviates peripheral secondary brain injury in rat cerebral hemorrhage model through promoting M2 polarization of microglial cells.
  Jiao, International immunopharmacology 2023 (PubMed)
  • GeneRIF: PPARgamma/RAD21 alleviates peripheral secondary brain injury in rat cerebral hemorrhage model through promoting M2 polarization of microglial cells.
• Activation of PPARγ prevents ferroptosis-induced damage through Nrf2/Gpx4 signaling pathway in rat hippocampus following epilepsy.
  Wang, Neuroreport 2023 (PubMed)
  • GeneRIF: Activation of PPARgamma prevents ferroptosis-induced damage through Nrf2/Gpx4 signaling pathway in rat hippocampus following epilepsy.
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