PaperBLAST

PaperBLAST Hits for 96 a.a. (TSTKIPSSSK...)

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>96 a.a. (TSTKIPSSSK...)
TSTKIPSSSKSSVTKQTKQKRNERERKRVDQVNQGFVLLQERVPKAAGNKAKLSKVETLR
EAARYIQELQKQLGMSSTSFHNSMPADFPTPEQSPV

Running BLASTp...

Found 51 similar proteins in the literature:

HLH3_CAEEL / Q22717 Helix-loop-helix protein 3 from Caenorhabditis elegans (see 4 papers)
NP_495938 Helix-loop-helix protein 3 from Caenorhabditis elegans
100% identity, 56% coverage

• function: Probable transcriptional regulator (PubMed:12874127, PubMed:18586090). May mediate transcriptional activation by binding to the E-box motif 5'-CANNTG-3' (PubMed:12874127, PubMed:9187144). Plays a role in the differentiation of the hermaphrodite-specific motor neurons (HSN) that are required for normal egg laying (PubMed:18586090). Might play a role in serotonin production by regulating expression of the tryptophan hydrolase tph-1 which catalyzes serotonin synthesis, in the HSN neurons (PubMed:18586090). Also plays a role in HSN axon guidance towards the vulva and the ventral nerve cord, possibly by promoting the expression of the netrin receptor unc-40 (PubMed:18586090). Under feeding conditions, involved in the regulation of the srh-234 chemoreceptor encoding gene expression in the ADL sensory neurons (PubMed:27487365). Together with hlh-2, involved in the induction of programmed cell death in the sister cells of the serotonergic neurosecretory motor (NSM) neurons, probably through the activation of egl-1 transcription (PubMed:12874127).
  subunit: Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with hlh-2.
  disruption phenotype: Egg-laying defective (PubMed:18586090). Reduced expression of the tryptophan hydroxylase tph-1 which leads to reduced production of the neurotransmitter serotonin in the hermaphrodite- specific motor neurons (HSN) (PubMed:18586090). Inappropriate lateral projection of HSN axons (PubMed:18586090). Lack of netrin receptor unc- 40 expression in a subset of HSN and VC motor neurons (PubMed:18586090). RNAi-mediated knockdown prevents cell death of a subset of the serotonergic neurosecretory motor (NSM) neuron sister cells, and survival of NSM sister cells is increased in an hlh-2 mutant background (PubMed:12874127).
• The CDK8 Complex and Proneural Proteins Together Drive Neurogenesis from a Mesodermal Lineage.
  Luo, Current biology : CB 2017
  • GeneRIF: CDK-8 Mediator kinase module acts together with a proneural protein, HLH-2, and in parallel to the proneural protein HLH-3 to promote I4 neurogenesis.
• HLH-3 is a C. elegans Achaete/Scute protein required for differentiation of the hermaphrodite-specific motor neurons.
  Doonan, Mechanisms of development (PubMed)
  • GeneRIF: The role of hlh-3 in nervous system development, is characterized.

ASCL5_MOUSE / M0QWB7 Achaete-scute homolog 5; Achaete-scute family bHLH transcription factor 5 from Mus musculus (Mouse) (see 3 papers)
NP_001257538 achaete-scute homolog 5 from Mus musculus
58% identity, 29% coverage

• function: Transcription factor (PubMed:30426815). Probably binds E-box motifs 5'-CANNTG-3' in complex with transcription factor TCF3/E12 (PubMed:30426815). Negatively modulates transcription of target genes such as CDH1/E-cadherin, perhaps by recruiting the PRC2 repressive complex to regulatory elements (PubMed:30426815, PubMed:30504223). Regulates ameloblast development and tooth germ growth, perhaps acting by positively modulating migration of inner enamel epithelium (IEE) cells (PubMed:30426815, PubMed:30504223, PubMed:34812512). Plays a role in enamel formation (PubMed:34812512).
  subunit: Interacts with transcription factor TCF3/E12.
  disruption phenotype: Knockout mice are fertile, but have enamel hypoplasia and small teeth (PubMed:30504223, PubMed:34812512). Abnormal ectopic expression of CDH1/E-cadherin in inner enamel epithelium (IEE) cells, but not in cells of the stratum intermedium (SI) at postnatal day 1 (P1) (PubMed:30504223). Inhibits the growth of clipped incisors (PubMed:30504223). Significantly reduces mRNA levels of SOX21, AMBN, ENAM, and AMELX in molars at P1 (PubMed:34812512). Develops fewer, smaller, incisors at 3 months of age in a transcription factor SP6/Epfn knockout background (PubMed:30504223). Epithelial cell invasion is inhibited and CDH1 ectopically expressed in dental epithelial cells at 3 months of age, in an SP6 knockout background (PubMed:30504223).
• The tooth-specific basic helix-loop-helix factor AmeloD promotes differentiation of ameloblasts.
  Jia, Journal of cellular physiology 2022 (PubMed)
  • GeneRIF: The tooth-specific basic helix-loop-helix factor AmeloD promotes differentiation of ameloblasts.
• Transcriptional regulation of the basic helix-loop-helix factor AmeloD during tooth development.
  Al, Journal of cellular physiology 2021 (PubMed)
  • GeneRIF: Transcriptional regulation of the basic helix-loop-helix factor AmeloD during tooth development.
• The transcription factor AmeloD stimulates epithelial cell motility essential for tooth morphology.
  Chiba, The Journal of biological chemistry 2019
  • GeneRIF: AmeloD stimulates epithelial cell motility essential for tooth morphology

HLH14_CAEEL / Q09961 Helix-loop-helix protein 14 from Caenorhabditis elegans (see 2 papers)
NP_495131 Helix-loop-helix protein 14 from Caenorhabditis elegans
50% identity, 42% coverage

• function: Probable transcription factor, involved in determining neuroblast cell fate, morphogenesis and aspects of terminal differentiation in both left/right symmetric and asymmetric neuronal lineages.
  disruption phenotype: RNAi-mediated knockdown disrupts differentiation of ASE L/R sensory neurons.
• HLH-14 is a C. elegans achaete-scute protein that promotes neurogenesis through asymmetric cell division.
  Frank, Development (Cambridge, England) 2003 (PubMed)
  • GeneRIF: characterization of HLH-14; propose that HLH-14 and HLH-2 act together to specify neuroblast lineages and promote neuronal fate

ASCL4_HUMAN / Q6XD76 Achaete-scute homolog 4; ASH-4; hASH4; Achaete-scute-like protein 4; Class A basic helix-loop-helix protein 44; bHLHa44 from Homo sapiens (Human) (see paper)
NP_982260 achaete-scute homolog 4 from Homo sapiens
45% identity, 40% coverage

• function: Could be a transcriptional regulator involved in skin development.
• Role of intramitochondrial arachidonic acid and acyl-CoA synthetase 4 in angiotensin II-regulated aldosterone synthesis in NCI-H295R adrenocortical cell line.
  Mele, Endocrinology 2012 (PubMed)
  • GeneRIF: intramitochondrial arachidonic acid and acyl-CoA synthetase 4 in angiotensin II-regulated aldosterone synthesis have roles in NCI-H295R adrenocortical cell line
• The XLMR gene ACSL4 plays a role in dendritic spine architecture.
  Meloni, Neuroscience 2009 (PubMed)
  • GeneRIF: In neuron reduced levels of ACSL4 led to a significant reduction in dendritic spine density and an alteration in spine/filopodia distribution.
• Hash4, a novel human achaete-scute homologue found in fetal skin.
  Jonsson, Genomics 2004 (PubMed)
  • GeneRIF: HASH4 is involved in skin development.

LOC107451231 achaete-scute homolog 1a from Parasteatoda tepidariorum
56% identity, 22% coverage

• Single-cell RNA sequencing of mid-to-late stage spider embryos: new insights into spider development
  Medina-Jiménez, BMC genomics 2024
  • “...assumption is the fact that the proneural gene achaete scute homolog 1 ( ash1 ) (LOC107451231) is also among the higher-ranked markers of Cluster-X. In Drosophila , achaete-scute complex genes are expressed in segregating neuroblasts (neuronal precursors), but not in neurons [ 25 , 174 ,...”

ASCL3_HUMAN / Q9NQ33 Achaete-scute homolog 3; ASH-3; hASH3; Class A basic helix-loop-helix protein 42; bHLHa42; bHLH transcriptional regulator Sgn-1 from Homo sapiens (Human) (see paper)
53% identity, 30% coverage

• function: Transcriptional repressor. Inhibits myogenesis. Plays a role in progenitor cells which differentiate into ductal and acinar, but not myoepithelial, cell lineages in the salivary glands. Involved in the functions of the microvillar cells and Bowman's glands and probably, in a non-cell-autonomous manner, in the development or regeneration of a complete olfactory epithelium (OE).
  subunit: Efficient DNA binding requires dimerization with another bHLH protein.

ASCL3_MOUSE / Q9JJR7 Achaete-scute homolog 3; ASH-3; mASH-3; mASH3; bHLH transcriptional regulator Sgn-1 from Mus musculus (Mouse) (see 4 papers)
NP_064435 achaete-scute homolog 3 from Mus musculus
53% identity, 32% coverage

• function: Transcriptional repressor (PubMed:11784080). Inhibits myogenesis (PubMed:11784080). Plays a role in progenitor cells which differentiate into ductal and acinar, but not myoepithelial, cell lineages in the salivary glands (PubMed:18572159, PubMed:21377457). Involved in the functions of the microvillar cells and Bowman's glands and probably, in a non-cell-autonomous manner, in the development or regeneration of a complete olfactory epithelium (OE) (PubMed:27910949).
  subunit: Efficient DNA binding requires dimerization with another bHLH protein.
  disruption phenotype: Viable and fertile (PubMed:21377457, PubMed:27910949). Salivary glands develop, but the submandibular glands are consistently smaller and overall levels of cell proliferation lower (PubMed:21377457). Expression of cation-chloride cotransporter Nkcc1 is dramatically reduced in salivary ducts (PubMed:21377457). No obvious morphological changes in the olfactory epithelium (OE) (PubMed:27910949).
• Ascl3 transcription factor marks a distinct progenitor lineage for non-neuronal support cells in the olfactory epithelium.
  Weng, Scientific reports 2016
  • GeneRIF: These results demonstrate that Ascl3 marks progenitors that are lineage-committed strictly to microvillar cells and Bowman's glands, and highlight the requirement for these cell types to support OE homeostasis.
• Ascl3 knockout and cell ablation models reveal complexity of salivary gland maintenance and regeneration.
  Arany, Developmental biology 2011
  • GeneRIF: Ascl3 knockouts develop smaller salivary glands than wild types, but secrete saliva normally. They display a lower level of cell proliferation, consistent with their smaller size. In the absence of Ascl3, the cells maintain their progenitor function.
• Ascl3 expression marks a progenitor population of both acinar and ductal cells in mouse salivary glands.
  Bullard, Developmental biology 2008
  • GeneRIF: These data demonstrate a progenitor-progeny relationship between duct cells and the acinar cell compartment, and identify a population of multipotent progenitor cells, marked by expression of Ascl3, which is capable of generating both gland cell types.

P10083 Achaete-scute complex protein T5 from Drosophila melanogaster
NP_476824 achaete from Drosophila melanogaster
41% identity, 32% coverage

• Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome
  Cornier, American journal of human genetics 2008
  • “...O73624 ; mouse Neurogenin-2, P70447 ; and Drosophila AS-C/T5, P10083 . Figure 3 Confirmation of Homozygosity for the MESP2 E103X Mutation as the Cause of STD...”
• HFR1 encodes an atypical bHLH protein that acts in phytochrome A signal transduction.
  Fairchild, Genes & development 2000
• Regulation of the Drosophila ID protein Extra macrochaetae by proneural dimerization partners.
  Li, eLife 2018
  • GeneRIF: Daughterless level sets Emc protein levels in most cells, apparently by stabilizing Emc in heterodimers. Emc is destabilized in proneural regions by local competition for heterodimer formation by proneural bHLH proteins including Atonal or AS-C proteins.
• Proneural proteins Achaete and Scute associate with nuclear actin to promote formation of external sensory organs.
  Hsiao, Journal of cell science 2014 (PubMed)
  • GeneRIF: Proneural proteins Achaete and Scute associate with nuclear actin to promote formation of external sensory organs.
• A conserved long noncoding RNA affects sleep behavior in Drosophila.
  Soshnev, Genetics 2011
  • GeneRIF: Data show that flies lacking yar RNAs are viable and show no overt morphological defects, consistent with maintained transcriptional regulation of the adjacent yellow (y) and achaete (ac) genes.
• The complex tale of the achaete-scute complex: a paradigmatic case in the analysis of gene organization and function during development.
  García-Bellido, Genetics 2009
  • GeneRIF: Studies of the AS-C has contributed to the understanding of eukaryotic gene organization and the dissection of the developmental mechanisms underlying pattern formation.
• How repeatable are associations between polymorphisms in achaete-scute and bristle number variation in Drosophila?
  Gruber, Genetics 2007
  • GeneRIF: quantified the relationship between achaete-scute complex (ASC) polymorphisms and bristle number phenotypes in several new population samples
• Linking pattern formation to cell-type specification: Dichaete and Ind directly repress achaete gene expression in the Drosophila CNS.
  Zhao, Proceedings of the National Academy of Sciences of the United States of America 2007
  • GeneRIF: Dichaete can physically interact with Ind and Vnd in the Drosophila central nervous system
• Delta and Hairy establish a periodic prepattern that positions sensory bristles in Drosophila legs.
  Joshi, Developmental biology 2006 (PubMed)
  • GeneRIF: The general model for generation of periodic pattern in the adult leg is a process involving broad and late activation of achaete
• Charlatan, a Zn-finger transcription factor, establishes a novel level of regulation of the proneural achaete/scute genes of Drosophila.
  Escudero, Development (Cambridge, England) 2005 (PubMed)
  • GeneRIF: overexpression of chn enhances expression and the formation of extra sensory organs
• More

AST4_DROME / P10084 Achaete-scute complex protein T4; Protein scute from Drosophila melanogaster (Fruit fly) (see 4 papers)
NP_476803 scute from Drosophila melanogaster
43% identity, 16% coverage

• function: AS-C proteins are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system. Also involved in sex determination and dosage compensation.
  subunit: Efficient DNA binding requires dimerization with another bHLH protein. Interacts with da (via bHLH motif). Interacts with Bap60.
• HFR1 encodes an atypical bHLH protein that acts in phytochrome A signal transduction.
  Fairchild, Genes & development 2000
• Transient Scute activation via a self-stimulatory loop directs enteroendocrine cell pair specification from self-renewing intestinal stem cells.
  Chen, Nature cell biology 2018 (PubMed)
  • GeneRIF: Here we show that, in intestinal stem cell lineages in adult Drosophila, in which the Delta-Notch-signalling-guided progenitor cell differentiation into enterocytes is the default mode, the specification of enteroendocrine cells (EEs) is initiated by transient Scute activation in a process driven by transcriptional self-stimulation combined with a negative feedback regulation between Scute and Notch targets.
• Transcription Factor Antagonism Controls Enteroendocrine Cell Specification from Intestinal Stem Cells.
  Li, Scientific reports 2017
  • GeneRIF: Results show that both Esg and Sc bind to a common promoter region of pros. Moreover, antagonistic activity between Esg and Sc controls the expression status of Pros in stem cells, thereby, specifying whether stem cells remain undifferentiated or commit to enteroendocrine cell differentiation.
• bHLH proteins involved in Drosophila neurogenesis are mutually regulated at the level of stability.
  Kiparaki, Nucleic acids research 2015
  • GeneRIF: Data show that bHLHb22 protein daughterless (Da) binding alters the turnover parameters of bHLHc28 protein scute (Sc).
• Proneural proteins Achaete and Scute associate with nuclear actin to promote formation of external sensory organs.
  Hsiao, Journal of cell science 2014 (PubMed)
  • GeneRIF: Proneural proteins Achaete and Scute associate with nuclear actin to promote formation of external sensory organs.
• How repeatable are associations between polymorphisms in achaete-scute and bristle number variation in Drosophila?
  Gruber, Genetics 2007
  • GeneRIF: quantified the relationship between achaete-scute complex (ASC) polymorphisms and bristle number phenotypes in several new population samples
• Role of the Sc C terminus in transcriptional activation and E(spl) repressor recruitment.
  Giagtzoglou, The Journal of biological chemistry 2005 (PubMed)
  • GeneRIF: the Sc C-terminal domain is required for E(spl) recruitment in an enhancer context-dependent fashion, suggesting that in some enhancers alternative interaction surfaces can be used to recruit E(spl) proteins
• Charlatan, a Zn-finger transcription factor, establishes a novel level of regulation of the proneural achaete/scute genes of Drosophila.
  Escudero, Development (Cambridge, England) 2005 (PubMed)
  • GeneRIF: overexpression of chn enhances expression and the formation of extra sensory organs
• achaete, but not scute, is dispensable for the peripheral nervous system of Drosophila.
  Marcellini, Developmental biology 2005 (PubMed)
  • GeneRIF: achaete, but not scute, is dispensable for development of the peripheral nervous system of Drosophila.
• More

XP_002058251 achaete-scute complex protein T4 from Drosophila virilis
43% identity, 16% coverage

• The pronotum LIM-HD gene tailup is both a positive and a negative regulator of the proneural genes achaete and scute of Drosophila.
  de, Mechanisms of development (PubMed)
  • GeneRIF: Tailup is required to activate achaete and scute at the dorsocentral region, probably by acting as an hexameric complex with the cofactor Chip and the transcriptional activator Sspd on the dorsocentral enhancer of the achaete-scute complex.

ASL1A_DANRE / Q90259 Achaete-scute homolog 1a; Zash-1a; Pituitary-absent protein from Danio rerio (Zebrafish) (Brachydanio rerio) (see 4 papers)
NP_571294 achaete-scute homolog 1a from Danio rerio
46% identity, 34% coverage

• function: Transcriptional regulator. May mediate transcription activation by binding to the E box-containing promoter (By similarity). Involved in neurogenesis. Required for the development of neurons in the epiphysis, acting partially redundantly with neurog1 and downstream of flh. Involved in maintaining rhombomere boundaries in the hindbrain, probably via up-regulation of delta expression. Also involved in pituitary development; required cell-autonomously in adenohypophyseal cells for endocrine differentiation and for survival of a subset of cells.
  subunit: Efficient DNA binding requires dimerization with another bHLH protein.
  disruption phenotype: In pituitary absent (pia) mutants, adenohypophyseal cells fail to express hormone genes and some become apoptotic.
• The proneural factors Ascl1a and Ascl1b contribute to the terminal differentiation of dopaminergic GABAergic dual transmitter neurons in zebrafish.
  Altbürger, Developmental biology 2024 (PubMed)
  • GeneRIF: The proneural factors Ascl1a and Ascl1b contribute to the terminal differentiation of dopaminergic GABAergic dual transmitter neurons in zebrafish.
• The bHLH transcription factor Ascl1a is essential for the specification of the intestinal secretory cells and mediates Notch signaling in the zebrafish intestine.
  Flasse, Developmental biology 2013 (PubMed)
  • GeneRIF: bHLH transcription factor Ascl1a is essential for the specification of the intestinal secretory cells and mediates Notch signaling in the zebrafish intestine
• Loss of ascl1a prevents secretory cell differentiation within the zebrafish intestinal epithelium resulting in a loss of distal intestinal motility.
  Roach, Developmental biology 2013
  • GeneRIF: Loss of ascl1a prevents secretory cell differentiation within the zebrafish intestinal epithelium resulting in a loss of distal intestinal motility
• The ascl1a and dlx genes have a regulatory role in the development of GABAergic interneurons in the zebrafish diencephalon.
  MacDonald, Developmental biology 2013
  • GeneRIF: dlx1a/2a act downstream of ascl1a but upstream of dlx5a/dlx6a and gad1b to activate GABAergic specification
• Ascl1a/Dkk/beta-catenin signaling pathway is necessary and glycogen synthase kinase-3beta inhibition is sufficient for zebrafish retina regeneration.
  Ramachandran, Proceedings of the National Academy of Sciences of the United States of America 2011
  • GeneRIF: Data show that injury-dependent induction of Ascl1a suppressed expression of the Wnt signaling inhibitor, Dkk, and induced expression of the Wnt ligand, Wnt4a.
• Ascl1a regulates Müller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway.
  Ramachandran, Nature cell biology 2010
  • GeneRIF: The Ascl1a regulates Muller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway.
• The proneural basic helix-loop-helix gene ascl1a is required for retina regeneration.
  Fausett, The Journal of neuroscience : the official journal of the Society for Neuroscience 2008
  • GeneRIF: ascl1a is essential for retina regeneration: within 4 h after retinal injury, ascl1a is induced in Muller glia.
• The proneural gene ascl1a is required for endocrine differentiation and cell survival in the zebrafish adenohypophysis.
  Pogoda, Development (Cambridge, England) 2006 (PubMed)
  • GeneRIF: Ascl1a might act downstream of diencephalic fibroblast growth factor 3 (Fgf3) signaling to mediate some of the effects of Fgf3 on the developing adenohypophysis
• More

P09775 Achaete-scute complex protein T8 from Drosophila melanogaster
NP_476694 asense from Drosophila melanogaster
50% identity, 10% coverage

• HFR1 encodes an atypical bHLH protein that acts in phytochrome A signal transduction.
  Fairchild, Genes & development 2000
• A novel proneural function of Asense is integrated with the sequential actions of Delta-Notch, L'sc and Su(H) to promote the neuroepithelial to neuroblast transition.
  Martin, PLoS genetics 2023
  • GeneRIF: A novel proneural function of Asense is integrated with the sequential actions of Delta-Notch, L'sc and Su(H) to promote the neuroepithelial to neuroblast transition.
• The Ets protein Pointed P1 represses Asense expression in type II neuroblasts by activating Tailless.
  Chen, PLoS genetics 2022
  • GeneRIF: The Ets protein Pointed P1 represses Asense expression in type II neuroblasts by activating Tailless.
• Tailless/TLX reverts intermediate neural progenitors to stem cells driving tumourigenesis via repression of asense/ASCL1.
  Hakes, eLife 2020
  • GeneRIF: Tailless/TLX reverts intermediate neural progenitors to stem cells driving tumourigenesis via repression of asense/ASCL1.
• Ets transcription factor Pointed promotes the generation of intermediate neural progenitors in Drosophila larval brains.
  Zhu, Proceedings of the National Academy of Sciences of the United States of America 2011
  • GeneRIF: PntP1 is both necessary and sufficient for the suppression of Ase in type II NBs and the generation of intermediate neural progenitor cells in Drosophila larval brains

Smp_015670 putative paraxis from Schistosoma mansoni
42% identity, 33% coverage

• Single-cell deconstruction of stem-cell-driven schistosome development
  Nanes, Trends in parasitology 2021
  • “...cabp (Smp_340130) myoD (Smp_167400) early muscle progenitors troponin + () cabp (Smp_340130) myoD (Smp_167400) tcf15 (Smp_015670) troponin (Smp_018250) late muscle progenitors tsp2 + tsp2 (Smp_335630) tegumental progenitors cpx + 7b2 (Smp_073270) cpx (Smp_050220) neural progenitors cb2 + cb2 (Smp_141610) intestinal/parenchymal progenitors hnf4 + hnf4 (Smp_174700) prom2...”

HLH6_CAEEL / Q10007 Helix-loop-helix protein 6 from Caenorhabditis elegans (see 2 papers)
NP_496070 Helix-loop-helix protein 6 from Caenorhabditis elegans
50% identity, 20% coverage

• function: Transcription factor that regulates the development of the g2 pharyngeal gland cells and pharyngeal gland function and thereby is required for feeding (PubMed:18927627). Required for the expression of a number of genes in the pharyngeal gland, possibly by binding to the E box motif (5'-CANNTG-3') in the promoter region of these genes (PubMed:18927627). Positively regulates the expression of genes encoding mucin-like proteins, which lubricate the pharyngeal tract to ensure efficient passage of the bacterial food source (PubMed:18927627). Exhibits pharyngeal gland-specific positive autoregulation activity (PubMed:17049341).
• The CSL transcription factor LAG-1 directly represses hlh-6 expression in C. elegans.
  Ghai, Developmental biology 2008 (PubMed)
  • GeneRIF: Regulation of hlh-6 by LAG-1 is strictly negative: removal of HRL1 or LAG-1 regulation results in ectopic expression of hlh-6, but does not affect expression in pharyngeal glands.
• The HLH-6 transcription factor regulates C. elegans pharyngeal gland development and function.
  Smit, PLoS genetics 2008
  • GeneRIF: Pharyngeal pumping in hlh-6 mutants is normal, but hlh-6 mutants lack expression of a class of mucin-related proteins that are normally secreted by pharyngeal glands and line the pharyngeal cuticle.
• Gland-specific expression of C. elegans hlh-6 requires the combinatorial action of three distinct promoter elements.
  Raharjo, Developmental biology 2007 (PubMed)
  • GeneRIF: The experiments identified three distinct regulatory elements required for hlh-6 expression: a PHA-4-binding site and two new elements, HRL1 and HRL2 (for hlh-6 regulatory elements 1 and 2).
• Transcriptional regulation of HLH-6-independent and subtype-specific genes expressed in the Caenorhabditis elegans pharyngeal glands.
  Ghai, Mechanisms of development (PubMed)
  • GeneRIF: Expression of the gland-expressed genes rely on cis-elements and trans-acting factor(s) other than HLH-6 and HRL3.

NP_989743 achaete-scute homolog 1 from Gallus gallus
58% identity, 21% coverage

• Interaction of MTG family proteins with NEUROG2 and ASCL1 in the developing nervous system.
  Aaker, Neuroscience letters 2010
  • GeneRIF: There is a functional relationship between specific MTG and bHLH proteins in developing chick spinal cord.
• Reprogramming chick RPE progeny cells to differentiate towards retinal neurons by ash1.
  Mao, Molecular vision 2008
  • GeneRIF: This study explores the possibility of reprogramming retinal pigment epithelium progeny cells to differentiate toward retinal neurons with achaete-scute homolog 1 (ash1), a proneural gene that is expressed in progenitor cells in the developing retina.
• A BMP-mediated transcriptional cascade involving Cash1 and Tlx-3 specifies first-order relay sensory neurons in the developing hindbrain.
  Hornbruch, Mechanisms of development 2005 (PubMed)
  • GeneRIF: a BMP-mediated transcriptional cascade involving Cash1 and Tlx-3 specifies first-order relay sensory neurons in the developing brainstem
• Interaction of Mash1 and Phox2b in sympathetic neuron development.
  Stanke, Molecular and cellular neurosciences 2004 (PubMed)
  • GeneRIF: induces neuronal differentiation characterized by the expression of generic neuronal genes SCG10, Hu and NF160

ASCL1_RAT / P19359 Achaete-scute homolog 1 from Rattus norvegicus (Rat) (see 2 papers)
NP_071779 achaete-scute homolog 1 from Rattus norvegicus
58% identity, 19% coverage

• function: Transcription factor that plays a key role in neuronal differentiation: acts as a pioneer transcription factor, accessing closed chromatin to allow other factors to bind and activate neural pathways (PubMed:10648228). Directly binds the E box motif (5'-CANNTG- 3') on promoters and promotes transcription of neuronal genes. The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro. Plays a role at early stages of development of specific neural lineages in most regions of the CNS, and of several lineages in the PNS. Essential for the generation of olfactory and autonomic neurons. Acts synergistically with FOXN4 to specify the identity of V2b neurons rather than V2a from bipotential p2 progenitors during spinal cord neurogenesis, probably through DLL4- NOTCH signaling activation. Involved in the regulation of neuroendocrine cell development in the glandular stomach (By similarity).
  subunit: Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with TCF3.
• HFR1 encodes an atypical bHLH protein that acts in phytochrome A signal transduction.
  Fairchild, Genes & development 2000
• MASH1 induces neuron transdifferentiation of adrenal medulla chromaffin cells.
  Peng, Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 2023
  • GeneRIF: MASH1 induces neuron transdifferentiation of adrenal medulla chromaffin cells.
• Mash-1 modified neural stem cells transplantation promotes neural stem cells differentiation into neurons to further improve locomotor functional recovery in spinal cord injury rats.
  Deng, Gene 2021 (PubMed)
  • GeneRIF: Mash-1 modified neural stem cells transplantation promotes neural stem cells differentiation into neurons to further improve locomotor functional recovery in spinal cord injury rats.
• Neuronal Trans-differentiation by Transcription Factors Ascl1 and Nurr1: Induction of a Dopaminergic Neurotransmitter Phenotype in Cortical GABAergic Neurons.
  Raina, Molecular neurobiology 2020 (PubMed)
  • GeneRIF: Neuronal Trans-differentiation by Transcription Factors Ascl1 and Nurr1: Induction of a Dopaminergic Neurotransmitter Phenotype in Cortical GABAergic Neurons.
• Ascl1 promotes tangential migration and confines migratory routes by induction of Ephb2 in the telencephalon.
  Liu, Scientific reports 2017
  • GeneRIF: Data found that Ascl1 promoted tangential migration along the ventricular zone/subventricular zone (VZ/SVZ) and intermediate zone (IZ) of the dorsal telencephalon. Also, Ascl1 induces Ephb2 expression in the telencephalon.
• MASH1/Ascl1a leads to GAP43 expression and axon regeneration in the adult CNS.
  Williams, PloS one 2015
  • GeneRIF: Data demonstrate that MASH1/Ascl1a is a fundamental regulator of axonal growth across vertebrates and can induce modifications to the intrinsic state of neurons to promote functional regeneration in response to central nervous system injury.
• MicroRNA-34a Promotes Hepatic Stellate Cell Activation via Targeting ACSL1.
  Yan, Medical science monitor : international medical journal of experimental and clinical research 2015
  • GeneRIF: miR-34a appears to play an important role in the process of liver fibrosis by targeting ACSL1 and may show promise as a therapeutic molecular target for hepatic fibrosis
• Shutdown of achaete-scute homolog-1 expression by heterogeneous nuclear ribonucleoprotein (hnRNP)-A2/B1 in hypoxia.
  Kasim, The Journal of biological chemistry 2014
  • GeneRIF: data suggest that a prominent down-regulation of hnRNP-A2/B1 during hypoxia is associated with the post-transcriptional suppression of hASH1 synthesis.
• Distinct functional brain regional integration of Casp3, Ascl1 and S100a6 gene expression in spatial memory.
  Gruden, Behavioural brain research 2013 (PubMed)
  • GeneRIF: S100a6/Casp gene expression between the prefrontal cortex and the cerebellum in spatial memory.
• More

ASCL1_MOUSE / Q02067 Achaete-scute homolog 1; ASH-1; mASH-1; mASH1 from Mus musculus (Mouse) (see 10 papers)
NP_032579 achaete-scute homolog 1 from Mus musculus
58% identity, 19% coverage

• function: Transcription factor that plays a key role in neuronal differentiation: acts as a pioneer transcription factor, accessing closed chromatin to allow other factors to bind and activate neural pathways (PubMed:24243019). Directly binds the E box motif (5'-CANNTG- 3') on promoters and promotes transcription of neuronal genes (PubMed:20107439, PubMed:24243019, PubMed:27281220). The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro (PubMed:20107439, PubMed:24243019, PubMed:27281220). Plays a role at early stages of development of specific neural lineages in most regions of the CNS, and of several lineages in the PNS (PubMed:8217843). Essential for the generation of olfactory and autonomic neurons (PubMed:8221886). Acts synergistically with FOXN4 to specify the identity of V2b neurons rather than V2a from bipotential p2 progenitors during spinal cord neurogenesis, probably through DLL4-NOTCH signaling activation (PubMed:16020526, PubMed:17728344). Involved in the regulation of neuroendocrine cell development in the glandular stomach (PubMed:18173746).
  subunit: Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with TCF3.
  disruption phenotype: Lethality at birth caused by severe defects in neurogenesis. While the brain and spinal cord of the mutants appear normal, their olfactory epithelium and sympathetic, parasympathetic and enteric ganglia are severely affected. In the olfactory epithelium, neuronal progenitors die at an early stage, whereas the non-neuronal supporting cells are present. In sympathetic ganglia, the development of neuronal precursors is arrested, preventing the generation of sympathetic neurons, without affecting glial precursor cells. Homozygous MASH1-null mice have smaller stomachs than the control, and neuroendocrine cells are mostly missing, while chief, parietal and pit cells are formed. However, the wall of the glandular stomach is much thicker, has a deeper fold structure, and the forestomach epithelium is villous compared to controls (PubMed:18173746).
• bHLH transcription factors Hes1, Ascl1 and Oligo2 exhibit different expression patterns in the process of physiological electric fields-induced neuronal differentiation.
  Li, Molecular biology reports 2024 (PubMed)
  • GeneRIF: bHLH transcription factors Hes1, Ascl1 and Oligo2 exhibit different expression patterns in the process of physiological electric fields-induced neuronal differentiation.
• Ascl1-expressing cell differentiation in initially developed taste buds and taste organoids.
  Matsuyama, Cell and tissue research 2023 (PubMed)
  • GeneRIF: Ascl1-expressing cell differentiation in initially developed taste buds and taste organoids.
• Ascl1 and Ngn2 convert mouse embryonic stem cells to neurons via functionally distinct paths.
  Vainorius, Nature communications 2023
  • GeneRIF: Ascl1 and Ngn2 convert mouse embryonic stem cells to neurons via functionally distinct paths.
• The bHLH transcription factor ASCL1 promotes differentiation of endocrine cells in the stomach and is regulated by Notch signaling.
  Hibdon, American journal of physiology. Gastrointestinal and liver physiology 2023
  • GeneRIF: The bHLH transcription factor ASCL1 promotes differentiation of endocrine cells in the stomach and is regulated by Notch signaling.
• Deletion of Ascl1 in pancreatic β-cells improves insulin secretion, promotes parasympathetic innervation, and attenuates dedifferentiation during metabolic stress.
  Osipovich, Molecular metabolism 2023
  • GeneRIF: Deletion of Ascl1 in pancreatic beta-cells improves insulin secretion, promotes parasympathetic innervation, and attenuates dedifferentiation during metabolic stress.
• Activation of Proneuronal Transcription Factor Ascl1 in Maternal Liver Ensures a Healthy Pregnancy.
  Lee, Cellular and molecular gastroenterology and hepatology 2022
  • GeneRIF: Activation of Proneuronal Transcription Factor Ascl1 in Maternal Liver Ensures a Healthy Pregnancy.
• IN BRAIN POST-ISCHEMIC PLASTICITY, Na+/Ca2+ EXCHANGER 1 AND Ascl1 INTERVENE IN MICROGLIA-DEPENDENT CONVERSION OF ASTROCYTES INTO NEURONAL LINEAGE.
  Casamassa, Cell calcium 2022 (PubMed)
  • GeneRIF: IN BRAIN POST-ISCHEMIC PLASTICITY, Na(+)/Ca(2+) EXCHANGER 1 AND Ascl1 INTERVENE IN MICROGLIA-DEPENDENT CONVERSION OF ASTROCYTES INTO NEURONAL LINEAGE.
• Mash1-expressing cells may be relevant to type III cells and a subset of PLCβ2-positive cell differentiation in adult mouse taste buds.
  Hsu, Cell and tissue research 2021 (PubMed)
  • GeneRIF: Mash1-expressing cells may be relevant to type III cells and a subset of PLCbeta2-positive cell differentiation in adult mouse taste buds.
• More
• Priorities and trends in the study of proteins in eye research, 1924-2014.
  Semba, Proteomics. Clinical applications 2015
  • “...Pou4f1 POU domain, class 4, transcription factor 1 71 probable transcription factor -- 1 isoform Q02067 Ascl1 Achaete-scute homolog 1 70 transcription factor -- 1 isoform P20444 Prkca protein kinase C alpha type 70 calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase expression of mutant form UV25...”
• Niche-independent symmetrical self-renewal of a mammalian tissue stem cell
  Conti, PLoS biology 2005
  • “...accession numbers for the genes and gene products discussed in this paper are Ascl1 (Mash1) (Q02067), Dlx2 (P40764), Egf (P01132), Emx2 (Q04744), Fabp7 (BLBP, B-FABP), (P51880), Fgf2 (bFGF) (P15655), Gad1 (Gad67) (P48318), Gfap (P03995), Nanog (Q7TN85), Nestin (Q6P5H2), Olig2 (Q9EQW6), Pax6 (P63015), Pax7 (P47239), Pou5f1 (Oct4,...”

ASCL1_HUMAN / P50553 Achaete-scute homolog 1; ASH-1; hASH1; Class A basic helix-loop-helix protein 46; bHLHa46 from Homo sapiens (Human) (see 2 papers)
NP_004307 achaete-scute homolog 1 from Homo sapiens
58% identity, 19% coverage

• function: Transcription factor that plays a key role in neuronal differentiation: acts as a pioneer transcription factor, accessing closed chromatin to allow other factors to bind and activate neural pathways. Directly binds the E box motif (5'-CANNTG-3') on promoters and promotes transcription of neuronal genes. The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro. Plays a role at early stages of development of specific neural lineages in most regions of the CNS, and of several lineages in the PNS. Essential for the generation of olfactory and autonomic neurons. Acts synergistically with FOXN4 to specify the identity of V2b neurons rather than V2a from bipotential p2 progenitors during spinal cord neurogenesis, probably through DLL4-NOTCH signaling activation. Involved in the regulation of neuroendocrine cell development in the glandular stomach (By similarity).
  subunit: Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with TCF3.
• Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq.
  Kingsley, Genes 2019
  • “...5 P28698 2 Ascl2 ARCAGCTGCY 7.06 10 4 Q99929 3 ASCL1 VSAGCAGCTGSNN 9.41 10 4 P50553 4 SP3 VCCACGCCCMC 1.42 10 3 Q02447 5 NEUROD1 NRACAGATGGYNN 1.60 10 3 Q13562 Lamina 1 SP2 GYCCCGCCYCYBSSS 8.51 10 15 Q02086 2 SP1 GCCCCKCCCCC 5.98 10 14 P08047 3...”
• Structural Features of Transcription Factors Associating with Nucleosome Binding.
  Fernandez, Molecular cell 2019
  • “...3D Structural Model Assemblies MYOG, CREM, and ASCL1/E12 structural models (SMR P15173, SMR Q03060, SMR P50553) were constructed based on SWISS-MODEL sequence alignment ( Bienert et al., 2017 ) with MYOD (pdb 1MDY) showing 74.2% DBD sequence identity, CREB1 (pdb 1DH3) showing 76.3% DBD sequence identity...”
  • “...al., 2011 ) and, GATA3 (pdb 4HC9) ( Chen et al., 2012 ). ASCL1 (SMR P50553). (B) Group IIA TFs with scissor-like DBDs crystal structures and extended recognition - helixes of cMYC/MAX (pdb 1NKP) ( Nair and Burley, 2003 ), CEBP (pdb 1NWQ) ( Miller et...”
• Genetically identified spinal interneurons integrating tactile afferents for motor control.
  Bui, Journal of neurophysiology 2015
• Phylogenetic analysis of the human basic helix-loop-helix proteins
  Ledent, Genome biology 2002
  • “...bHLH genes from Homo sapiens Sequence identification Gene name Family Mouse ortholog(s) Contigs Chromosome localization P50553 Hash1 Achaete-Scute a Mash1 NT_009439.3 12q22-q23 Q99929 Hash2 Achaete-Scute a Mash2 NT_009368.3 11p15.5 N024228 Hash3a * Achaete-Scute b Mash3 NT_024228.3 11p15.3 N004680 Hash3b * Achaete-Scute b ? NT_004680.3 1q31-q32 N009720...”
  • “...bHLH genes from Mus musculus Gene name Family Human ortholog(s) Accession number Mash1 Achaete-Scute a P50553 gb|AAB28830.1 Mash2 Achaete-Scute a Q99929 gb|AAD33794.1 Mash3 Achaete-Scute b N024228 sp|CAC37689 Myogenin MyoD P15173 sp|P12979 Myf6 MyoD P23409 ref|NP_032683.1 MyoD MyoD P15172 sp|P10085 Myf5 MyoD P13349 ref|NP_032682.1 E2A E12/E47 N011269...”
• Further description of two individuals with de novo p.(Glu127Lys) missense variant in the ASCL1 gene.
  Malbos, Clinical genetics 2024 (PubMed)
  • GeneRIF: Further description of two individuals with de novo p.(Glu127Lys) missense variant in the ASCL1 gene.
• Identification of molecular subtypes based on chromatin regulator-related genes and experimental verification of the role of ASCL1 in conferring chemotherapy resistance to breast cancer.
  Li, Frontiers in immunology 2024
  • GeneRIF: Identification of molecular subtypes based on chromatin regulator-related genes and experimental verification of the role of ASCL1 in conferring chemotherapy resistance to breast cancer.
• Transcription factor ASCL1 targets SLC6A13 to inhibit the progression of hepatocellular carcinoma via the glycine-inflammasome signaling.
  Zhang, Biomolecules & biomedicine 2024
  • GeneRIF: Transcription factor ASCL1 targets SLC6A13 to inhibit the progression of hepatocellular carcinoma via the glycine-inflammasome signaling.
• Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus.
  Vink, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2023
  • GeneRIF: Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus.
• An integrative epigenomic approach identifies ELF3 as an oncogenic regulator in ASCL1-positive neuroendocrine carcinoma.
  Horie, Cancer science 2023
  • GeneRIF: An integrative epigenomic approach identifies ELF3 as an oncogenic regulator in ASCL1-positive neuroendocrine carcinoma.
• ASCL1 is activated downstream of the ROR2/CREB signaling pathway to support lineage plasticity in prostate cancer.
  Tabrizian, Cell reports 2023 (PubMed)
  • GeneRIF: ASCL1 is activated downstream of the ROR2/CREB signaling pathway to support lineage plasticity in prostate cancer.
• Ubiquitination of ASCL1 mediates CD47 transcriptional activation of the AKT signaling pathway, and glycolysis promotes osteogenic differentiation of hBMSCs.
  Zhang, In vitro cellular & developmental biology. Animal 2023
  • GeneRIF: Ubiquitination of ASCL1 mediates CD47 transcriptional activation of the AKT signaling pathway, and glycolysis promotes osteogenic differentiation of hBMSCs.
• ASCL1 Is Involved in the Pathogenesis of Schizophrenia by Regulation of Genes Related to Cell Proliferation, Neuronal Signature Formation, and Neuroplasticity.
  Abashkin, International journal of molecular sciences 2023
  • GeneRIF: ASCL1 Is Involved in the Pathogenesis of Schizophrenia by Regulation of Genes Related to Cell Proliferation, Neuronal Signature Formation, and Neuroplasticity.
• More

ASCL1_XENLA / Q06234 Achaete-scute homolog 1; XASH1 from Xenopus laevis (African clawed frog) (see paper)
NP_001079247 achaete-scute homolog 1 from Xenopus laevis
46% identity, 34% coverage

• function: Transcription factor that plays a key role in neuronal differentiation: acts as a pioneer transcription factor, accessing closed chromatin to allow other factors to bind and activate neural pathways (By similarity). Directly binds the E box motif (5'-CANNTG-3') on promoters and promotes transcription of neuronal genes (PubMed:8443105). The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro (By similarity).
  subunit: Efficient DNA binding requires dimerization with another bHLH protein.
• A novel role for Ascl1 in the regulation of mesendoderm formation via HDAC-dependent antagonism of VegT.
  Gao, Development (Cambridge, England) 2016
  • GeneRIF: These results establish maternal Asc1l as a key factor in establishing pre-patterning of the early embryo, acting in opposition to VegT and biasing the animal pole to adopt neural fates.
• The phosphorylation status of Ascl1 is a key determinant of neuronal differentiation and maturation in vivo and in vitro.
  Ali, Development (Cambridge, England) 2014 (PubMed)
  • GeneRIF: analysis of cell-cycle-dependent phosphorylation of the key reprogramming transcription factor Ascl1 on multiple serine-proline sites

ASL1B_DANRE / Q90260 Achaete-scute homolog 1b; Zash-1b from Danio rerio (Zebrafish) (Brachydanio rerio) (see 3 papers)
NP_571306 achaete-scute homolog 1b from Danio rerio
57% identity, 24% coverage

• function: Transcriptional regulator. May mediate transcription activation by binding to the E box-containing promoter (By similarity). Involved in neurogenesis. Involved in maintaining rhombomere boundaries in the hindbrain, probably via up-regulation of delta expression. May mediate transcription activation by binding to the E box-containing promoter.
  subunit: Efficient DNA binding requires dimerization with another bHLH protein.
• The proneural factors Ascl1a and Ascl1b contribute to the terminal differentiation of dopaminergic GABAergic dual transmitter neurons in zebrafish.
  Altbürger, Developmental biology 2024 (PubMed)
  • GeneRIF: The proneural factors Ascl1a and Ascl1b contribute to the terminal differentiation of dopaminergic GABAergic dual transmitter neurons in zebrafish.
• MASH1/Ascl1a leads to GAP43 expression and axon regeneration in the adult CNS.
  Williams, PloS one 2015
  • GeneRIF: Data demonstrate that MASH1/Ascl1a is a fundamental regulator of axonal growth across vertebrates and can induce modifications to the intrinsic state of neurons to promote functional regeneration in response to central nervous system injury.
• Valproic acid silencing of ascl1b/Ascl1 results in the failure of serotonergic differentiation in a zebrafish model of fetal valproate syndrome.
  Jacob, Disease models & mechanisms 2014
  • GeneRIF: ascl1b/Ascl1 silencing by valproic acid results in the failure of serotonergic differentiation in a zebrafish model of fetal valproate syndrome
• Ascl1b and Neurod1, instead of Neurog3, control pancreatic endocrine cell fate in zebrafish.
  Flasse, BMC biology 2013
  • GeneRIF: The control of endocrine cell fate is instead fulfilled by two basic helix-loop-helix factors, Ascl1b and Neurod1 and NEUROG3 is not the unique pancreatic endocrine cell fate determinant in vertebrates.

XP_974297 basic helix-loop-helix transcription factor amos from Tribolium castaneum
42% identity, 40% coverage

• Functional characterization of PAS and HES family bHLH transcription factors during the metamorphosis of the red flour beetle, Tribolium castaneum
  Bitra, Gene 2009
  • “...XP_974793 GLEAN_14712 TcHLH4C XP_971274 GLEAN_07725 TcNautilus XP_972025 GLEAN_15855 TcCato XP_974243 GLEAN_03171 TcAtonal XP_970709 GLEAN_11336 TcAmos XP_974297 GLEAN_03170 TcScute - GLEAN_07826 TcAsense NP_001034533 GLEAN_08437 TcAsh NP_001034537 GLEAN_08433 TcDaughterless XP_973272 GLEAN_09743 TcEmc XP_970015 GLEAN_00024 TcMitf XP_975837 GLEAN_14225 Table 2 a. Amino acid identity of bHLH-PAS and HES genes...”

NP_731326 salivary gland-expressed bHLH, isoform C from Drosophila melanogaster
39% identity, 22% coverage

• Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA.
  Fox, Development (Cambridge, England) 2013
  • GeneRIF: Sage, a bHLH transcription factor expressed exclusively in the Drosophila salivary gland (SG), is required for late SG survival and normal tube morphology and provides tissue specificity to FoxA
• Fork head and Sage maintain a uniform and patent salivary gland lumen through regulation of two downstream target genes, PH4alphaSG1 and PH4alphaSG2.
  Abrams, Development (Cambridge, England) 2006 (PubMed)
  • GeneRIF: Sage cooperates with Fkh to directly regulate expression of PH4alphaSG2, as well as sage itself, and to indirectly regulate expression of PH4alphaSG1.

NGN3_MOUSE / P70661 Neurogenin-3; NGN-3; Helix-loop-helix protein mATH-4B; mATH4B; Protein atonal homolog 5 from Mus musculus (Mouse) (see 3 papers)
NP_033849 neurogenin-3 from Mus musculus
35% identity, 36% coverage

• function: Acts as a transcriptional regulator. Together with NKX2-2, initiates transcriptional activation of NEUROD1. Involved in neurogenesis. Also required for the specification of a common precursor of the 4 pancreatic endocrine cell types.
  subunit: Efficient DNA binding requires dimerization with another bHLH protein. Interacts with ATOH8.
• USP7 controls NGN3 stability and pancreatic endocrine lineage development.
  Manea, Nature communications 2023
  • GeneRIF: USP7 controls NGN3 stability and pancreatic endocrine lineage development.
• Reduced Neurog3 Gene Dosage Shifts Enteroendocrine Progenitor Towards Goblet Cell Lineage in the Mouse Intestine.
  Li, Cellular and molecular gastroenterology and hepatology 2021
  • GeneRIF: Reduced Neurog3 Gene Dosage Shifts Enteroendocrine Progenitor Towards Goblet Cell Lineage in the Mouse Intestine.
• H3K4 Trimethylation Is Required for Postnatal Pancreatic Endocrine Cell Functional Maturation.
  Campbell, Diabetes 2021 (PubMed)
  • GeneRIF: H3K4 Trimethylation Is Required for Postnatal Pancreatic Endocrine Cell Functional Maturation.
• Ngn3-Positive Cells Arise from Pancreatic Duct Cells.
  Kimura-Nakajima, International journal of molecular sciences 2021
  • GeneRIF: Ngn3-Positive Cells Arise from Pancreatic Duct Cells.
• Null mutations of NEUROG3 are associated with delayed-onset diabetes mellitus.
  Solorzano-Vargas, JCI insight 2020
  • GeneRIF: Null mutations of NEUROG3 are associated with delayed-onset diabetes mellitus.
• SOX3 promotes generation of committed spermatogonia in postnatal mouse testes.
  McAninch, Scientific reports 2020
  • GeneRIF: SOX3 promotes generation of committed spermatogonia in postnatal mouse testes.
• Estradiol-dependent axogenesis and Ngn3 expression are determined by XY sex chromosome complement in hypothalamic neurons.
  Cisternas, Scientific reports 2020
  • GeneRIF: Estradiol-dependent axogenesis and Ngn3 expression are determined by XY sex chromosome complement in hypothalamic neurons.
• Silk Fibroin Promotes the Regeneration of Pancreatic β-Cells in the C57BL/KsJ-Leprdb/db Mouse.
  Park, Molecules (Basel, Switzerland) 2020
  • GeneRIF: Silk Fibroin Promotes the Regeneration of Pancreatic beta-Cells in the C57BL/KsJ-Lepr(db/db) Mouse.
• More

ASCL2_RAT / P19360 Achaete-scute homolog 2; Mash2 from Rattus norvegicus (Rat) (see 3 papers)
XP_063136213 achaete-scute homolog 2 isoform X1 from Rattus norvegicus
56% identity, 17% coverage

• function: Transcription factor (PubMed:1314394). Binds to E-box motifs 5'-CANNTG-3' in the regulatory elements of target genes, probably as a heterodimer with another basic helix-loop-helix (bHLH) protein such as the transcription factor TCF3. May bind both open and closed chromatin, acting as a pioneer transcription factor to allow other factors to bind and activate lineage-specific genes. Required during post-implantation development for the generation of some differentiated trophoblast cell types. Transcriptional activity of ASCL2 may be antagonised in a subset of trophoblast cells by bHLH transcription factor HAND1, perhaps by competing for dimerization with other bHLH proteins. Involved in differentiation and function of follicular T-helper (Tfh) cells, thereby playing a role in germinal center responses; probably modulates expression of genes involved in Tfh cell function, such as BCL6. May also act as a suppressor of Th1-, Th2- and Th17-cell differentiation. Induces the formation of stem cells in intestinal crypts in vitro, synergistically activating transcription of target genes, such as SOX9, together with TCF4/beta-catenin. May form a bistable transcriptional switch, controlling expression of its own gene together with Wnt/R- spondin signaling, and thereby maintaining stem cell characteristics (By similarity). Modulates expression of target genes, including perhaps down-regulating EGR1/Krox24 and chemokine CXCL10/Mob-1 and up- regulating CXCR4 and CDKN1C/p57kip2, in Schwann cells (PubMed:12196582). May play a role in reducing proliferation of Schwann cells, perhaps acting via modulation of expression of CDKN1C (PubMed:12196582). May be dispensable for blastocyst formation and later embryonic function (By similarity). May be involved in the determination of neuronal precursors (PubMed:2392153).
  subunit: Efficient DNA binding requires dimerization with another bHLH protein (PubMed:1314394). Forms heterodimers with bHLH transcription factor TCF3 (PubMed:1314394). May not heterodimerise with bHLH protein HAND1 (By similarity).
• ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development.
  Varberg, Proceedings of the National Academy of Sciences of the United States of America 2021
  • GeneRIF: ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development.
• HFR1 encodes an atypical bHLH protein that acts in phytochrome A signal transduction.
  Fairchild, Genes & development 2000

NP_067732 neurogenin-3 from Rattus norvegicus
35% identity, 36% coverage

• Activation of the developmental pathway neurogenin-3/microRNA-7a regulates cholangiocyte proliferation in response to injury.
  Marzioni, Hepatology (Baltimore, Md.) 2014 (PubMed)
  • GeneRIF: Activation of the developmental pathway neurogenin-3/microRNA-7a regulates cholangiocyte proliferation in response to injury.
• Short-reactivation of neurogenin-3 and mesenchymal microenvironment is require for β-cells differentiation during fetal pancreas development and islet regeneration.
  Yang, Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 2014 (PubMed)
  • GeneRIF: The expression of transcription factor Ngn3 and pancreatic mesenchymal microenvironment are important and necessary to promote pancreatic progenitors differentiated to islet cells regardless of pancreatic development or islets regeneration.
• Streptozotocin-induced expression of Ngn3 and Pax4 in neonatal rat pancreatic α-cells.
  Liang, World journal of gastroenterology 2011
  • GeneRIF: Data show that Ngn3 and Pax4, a transcription factor that lies downstream of Ngn3 and plays an important role in beta-cell differentiation, were expressed in the alpha-cells of STZ-treated rats.
• OVO homologue-like 1 (Ovol1) transcription factor: a novel target of neurogenin-3 in rodent pancreas.
  Vetere, Diabetologia 2010
  • GeneRIF: OVOL1, a downstream target of NGN3, may play an important role in regulating the balance between proliferation and differentiation of pancreatic cells
• Combined expression of transcription factors induces AR42J-B13 cells to differentiate into insulin-producing cells.
  Ogihara, Endocrine journal 2008 (PubMed)
  • GeneRIF: Ngn3 expressed together with Nkx6.1 or MafA induces AR42J-B13 cells to differentiate into insulin-producing cells, supporting the use of these cells as a model system for studying beta-cell differentiation in vitro.
• Glucose is necessary for embryonic pancreatic endocrine cell differentiation.
  Guillemain, The Journal of biological chemistry 2007 (PubMed)
  • GeneRIF: glucose interferes with the pancreatic endocrine cells development by regulating the transition between Ngn3 and upstream NeuroD.
• Ngn3 expression during postnatal in vitro beta cell neogenesis induced by the JAK/STAT pathway.
  Baeyens, Cell death and differentiation 2006 (PubMed)
  • GeneRIF: Rat exocrine pancreas treated with epidermal growth factor and leukaemia inhibitory factor induced a transient expression of both Ngn3 and its upstream activator hepatocyte nuclear factor 6.
• Neurogenin3 participates in gliogenesis in the developing vertebrate spinal cord.
  Lee, Developmental biology 2003 (PubMed)
  • GeneRIF: role in regulating glial differentiation at a developmental stage prior to the segregation of the oligodendrocyte and astrocyte lineage

ASCL2_MOUSE / O35885 Achaete-scute homolog 2; ASH-2; mASH-2; mASH2 from Mus musculus (Mouse) (see 7 papers)
NP_032580 achaete-scute homolog 2 from Mus musculus
56% identity, 17% coverage

• function: Transcription factor (PubMed:10611232, PubMed:29500235). Binds to E-box motifs 5'-CANNTG-3' in the regulatory elements of target genes, probably as a heterodimer with another basic helix-loop-helix (bHLH) protein such as the transcription factor TCF3 (PubMed:10611232, PubMed:29500235). May bind both open and closed chromatin, acting as a pioneer transcription factor to allow other factors to bind and activate lineage-specific genes (PubMed:29500235). Required during post-implantation development for the generation of some differentiated trophoblast cell types (PubMed:8090202). Transcriptional activity of ASCL2 may be antagonised in a subset of trophoblast cells by bHLH transcription factor HAND1, perhaps by competing for dimerization with other bHLH proteins (PubMed:10611232). Involved in differentiation and function of follicular T-helper (Tfh) cells, thereby playing a role in germinal center responses; probably modulates expression of genes involved in Tfh cell function, such as BCL6 (PubMed:24463518). May also act as a suppressor of Th1-, Th2- and Th17-cell differentiation (PubMed:24463518). Induces the formation of stem cells in intestinal crypts in vitro, synergistically activating transcription of target genes, such as SOX9, together with TCF4/beta-catenin (PubMed:25620640). May form a bistable transcriptional switch, controlling expression of its own gene together with Wnt/R-spondin signaling, and thereby maintaining stem cell characteristics (PubMed:25620640). Modulates expression of target genes, including perhaps down-regulating EGR1/Krox24 and chemokine CXCL10/Mob-1 and up-regulating CXCR4 and CDKN1C/p57kip2, in Schwann cells (By similarity). May play a role in reducing proliferation of Schwann cells, perhaps acting via modulation of expression of CDKN1C (By similarity). May be dispensable for blastocyst formation and later embryonic function (PubMed:8090202, PubMed:9622625). May be involved in the determination of neuronal precursors (By similarity).
  subunit: Efficient DNA binding requires dimerization with another basic helix-loop-helix (bHLH) protein (PubMed:10611232). Forms heterodimers with bHLH transcription factor TCF3 (PubMed:10611232). May not heterodimerise with bHLH protein HAND1 (PubMed:10611232).
  disruption phenotype: Embryonic lethality between 9.5 and 10.5 days post coitum (dpc) (PubMed:7773285, PubMed:8090202). Abnormalities in extraembryonic trophoblast cell types; by 8.5 dpc, the ectoplacental cone (EPC) lacks diploid precursors and by 9.5-10.5 dpc, the spongiotrophoblast layer of the placenta is missing and the labyrinthine layer lacks normal highly vascularized organization (PubMed:7773285, PubMed:8090202). Unexpectedly, does not exacerbate trophoblast phenotype at 8.5 dpc when combined with simultaneous knockout of basic helix-loop-helix transcription factor HAND1 (PubMed:10611232). Conditional knockout targeted at cells expressing T- cell surface glycoprotein CD4 causes loss of body weight from day 3 to day 9 after influenza infection; 5-fold higher levels of viral hemagglutinin mRNA in lungs, by comparison with controls (PubMed:24463518). Lung-draining lymph nodes contain less than half normal level of follicular T-helper (Tfh) cells (PubMed:24463518). Development of Tfh cells and germinal center B-cells is reduced in the spleen (PubMed:24463518). Increased expression of TCF3/E47 in Tfh and naive T-cells (PubMed:24463518).
• A role of Achaete-scute complex homolog 2 in T follicular regulatory cell development.
  Iida, Biochemical and biophysical research communications 2023 (PubMed)
  • GeneRIF: A role of Achaete-scute complex homolog 2 in T follicular regulatory cell development.
• ASCL2 induces an immune excluded microenvironment by activating cancer-associated fibroblasts in microsatellite stable colorectal cancer.
  Zhang, Oncogene 2023
  • GeneRIF: ASCL2 induces an immune excluded microenvironment by activating cancer-associated fibroblasts in microsatellite stable colorectal cancer.
• Transcription factor Ascl2 promotes germinal center B cell responses by directly regulating AID transcription.
  Sun, Cell reports 2021 (PubMed)
  • GeneRIF: Transcription factor Ascl2 promotes germinal center B cell responses by directly regulating AID transcription.
• Hyperactivated Wnt-β-catenin signaling in the absence of sFRP1 and sFRP5 disrupts trophoblast differentiation through repression of Ascl2.
  Bao, BMC biology 2020
  • GeneRIF: Hyperactivated Wnt-beta-catenin signaling in the absence of sFRP1 and sFRP5 disrupts trophoblast differentiation through repression of Ascl2.
• Transcription factor ASCL2 is required for development of the glycogen trophoblast cell lineage.
  Bogutz, PLoS genetics 2018
  • GeneRIF: ASCL2 is required for the emergence or early maintenance of glycogen trophoblast cells during development.
• Ascl2 inhibits myogenesis by antagonizing the transcriptional activity of myogenic regulatory factors.
  Wang, Development (Cambridge, England) 2017
  • GeneRIF: Ascl2 inhibits myogenic differentiation by targeting MRFs and facilitates the generation of postnatal satellite cells.
• Increased dosage of the imprinted Ascl2 gene restrains two key endocrine lineages of the mouse Placenta.
  Tunster, Developmental biology 2016
  • GeneRIF: overexpression of the imprinted Ascl2 gene has considerable consequences for placental development, specifically for the parietal trophoblast giant cell and spongiotrophoblast lineages both of which express pregnancy-related hormones.
• Ascl2 acts as an R-spondin/Wnt-responsive switch to control stemness in intestinal crypts.
  Schuijers, Cell stem cell 2015 (PubMed)
  • GeneRIF: The ascl2 forms a transcriptional switch that is both Wnt responsive and Wnt dependent to define stem cell identity.
• More

BHA15_RAT / P70562 Class A basic helix-loop-helix protein 15; bHLHa15; Class B basic helix-loop-helix protein 8; bHLHb8; Muscle, intestine and stomach expression 1; MIST-1 from Rattus norvegicus (Rat) (see paper)
NP_036995 class A basic helix-loop-helix protein 15 from Rattus norvegicus
38% identity, 39% coverage

• function: Plays a role in controlling the transcriptional activity of MyoD, ensuring that expanding myoblast populations remain undifferentiated. Repression may occur through muscle-specific E-box occupancy by homodimers. May also negatively regulate bHLH-mediated transcription through an N-terminal repressor domain. Serves as a key regulator of acinar cell function, stability, and identity. Also required for normal organelle localization in exocrine cells and for mitochondrial calcium ion transport. May function as a unique regulator of gene expression in several different embryonic and postnatal cell lineages. Binds to the E-box consensus sequence 5'-CANNTG-3' (By similarity).
  subunit: Forms homodimers or heterodimers with TCF3 gene products E12 and E47. These dimers bind to the E-box site, however, heterodimer with MYOD1 does not bind target DNA
• The bHLH domain of Mistl is sufficient to activate gene transcription.
  Tran, Gene expression 2007
  • GeneRIF: Data suggest that Mist1 activates exocrine-specific gene transcription through an acetylation mechanism.
• Role of basic helix-loop-helix (bHLH) and CREB transcription factors in the regulation of Sertoli cell androgen-binding protein expression.
  Saxlund, Molecular reproduction and development 2004 (PubMed)
  • GeneRIF: bHLH regulate ABP in differentiated Sertoli cells.

HLH4_CAEEL / P34555 Helix-loop-helix protein 4 from Caenorhabditis elegans (see 2 papers)
NP_001379052 Helix-loop-helix protein 4 from Caenorhabditis elegans
41% identity, 26% coverage

• function: Acts as a transcriptional regulator (PubMed:27487365, PubMed:29672507). May mediate transcriptional activation by binding to the E-box motif 5'-CANNTG-3' (PubMed:29672507). Required for the correct morphology, terminal identity and function of the ADL sensory neurons by controlling the expression of the ADL-specific gene repertoire, including chemoreceptor encoding genes, ion channel encoding genes, neuropeptides and the neurotransmitter eat-4 (PubMed:29672507). Regulates the expression of the srh-234 chemoreceptor encoding gene in the ADL neurons under feeding conditions (PubMed:27487365). Plays a role in the chemorepulsive response toward ascaroside pheromones mediated by the ADL sensory neurons (PubMed:29672507).
  disruption phenotype: RNAi-mediated knockdown in a rrf-3 RNAi hypersensitive mutant background leads to decreased expression of srh- 234 in the cell body of ADL sensory neurons (PubMed:27487365).
• Unconventional function of an Achaete-Scute homolog as a terminal selector of nociceptive neuron identity.
  Masoudi, PLoS biology 2018
  • GeneRIF: Unconventional function of an Achaete-Scute homolog, hlh-4, as a terminal selector of nociceptive neuron identity, has been reported.

BHA15_MOUSE / Q9QYC3 Class A basic helix-loop-helix protein 15; bHLHa15; Class B basic helix-loop-helix protein 8; bHLHb8; Muscle, intestine and stomach expression 1; MIST-1 from Mus musculus (Mouse) (see 6 papers)
38% identity, 39% coverage

• function: Plays a role in controlling the transcriptional activity of MyoD, ensuring that expanding myoblast populations remain undifferentiated (PubMed:17612490). Repression may occur through muscle-specific E-box occupancy by homodimers. May also negatively regulate bHLH-mediated transcription through an N-terminal repressor domain. Serves as a key regulator of acinar cell function, stability, and identity. Also required for normal organelle localization in exocrine cells and for mitochondrial calcium ion transport. May function as a unique regulator of gene expression in several different embryonic and postnatal cell lineages. Binds to the E-box consensus sequence 5'-CANNTG-3'.
  subunit: Forms homodimers or heterodimers with TCF3 gene products E12 and E47. These dimers bind to the E-box site, however, heterodimer with MYOD1 does not bind target DNA
  disruption phenotype: Mice display incorrect granule organization in pancreatic acinar cells and other serous exocrine cells such as parotid acini and gastric chief cells. They also display mislocalization of mitochondria and Golgi apparatus and reduced Ca(2+) uptake by mitochondria.

HLH12_CAEEL / Q18277 Helix-loop-helix protein hlh-12 from Caenorhabditis elegans (see 2 papers)
NP_501445 Helix-loop-helix protein hlh-12 from Caenorhabditis elegans
41% identity, 48% coverage

• function: Transcription factor which binds the E box motif 5'-GCAGGTG- 3' (PubMed:17588558). Involved in migration of the gonadal leader cells; distal tip cells (DTCs) in hermaphrodites, and linker cells in males (PubMed:17588558, PubMed:25982859). Positively regulates expression of alpha integrin ina-1 and ADAMTS protease gon-1 (PubMed:17588558, PubMed:25982859).
  subunit: Forms a heterodimer with helix-loop-helix protein hlh-2.
  disruption phenotype: RNAi-mediated knockdown reduces expression of alpha integrin ina-1 and ADAMTS protease gon-1, and causes defects in migration of the gonadal distal tip cells (DTCs).
• hlh-12, a gene that is necessary and sufficient to promote migration of gonadal regulatory cells in Caenorhabditis elegans, evolved within the Caenorhabditis clade.
  Littleford, Genetics 2021
  • GeneRIF: hlh-12, a gene that is necessary and sufficient to promote migration of gonadal regulatory cells in Caenorhabditis elegans, evolved within the Caenorhabditis clade.

NP_990277 transcription factor 15 from Gallus gallus
39% identity, 38% coverage

• beta-Catenin-dependent Wnt signalling controls the epithelial organisation of somites through the activation of paraxis.
  Linker, Development (Cambridge, England) 2005 (PubMed)
  • GeneRIF: beta-catenin activity, initiated by Wnt6 and mediated by paraxis, is required for the maintenance of the epithelial structure of somites

TCF15_CHICK / P79782 Transcription factor 15; TCF-15; Paraxis; Protein bHLH-EC2 from Gallus gallus (Chicken) (see 2 papers)
39% identity, 38% coverage

• function: Early transcription factor that plays a key role in somitogenesis, paraxial mesoderm development and regulation of stem cell pluripotency. Essential for the mesenchymal to epithelial transition associated with somite formation. Required for somite morphogenesis, thereby regulating patterning of the axial skeleton and skeletal muscles. Also plays a key role in regulation of stem cell pluripotency. Promotes pluripotency exit of embryonic stem cells (ESCs) by priming ESCs for differentiation. Acts as a key regulator of self- renewal of hematopoietic stem cells (HSCs) by mediating HSCs quiescence and long-term self-renewal. Acts by forming a heterodimer with another helix-loop-helix (bHLH) protein, that binds DNA on E-box motifs (5'- CANNTG-3') and activates transcription of target genes.
  subunit: Heterodimer; efficient DNA binding requires dimerization with another bHLH protein.

XP_017899088 achaete-scute homolog 2 from Capra hircus
53% identity, 23% coverage

• ALAS1 associated with goat kidding number trait was regulated by the transcription factor ASCL2 to affect granulosa cell proliferation.
  Li, Animal genetics 2023 (PubMed)
  • GeneRIF: ALAS1 associated with goat kidding number trait was regulated by the transcription factor ASCL2 to affect granulosa cell proliferation.

NDF1_CAEEL / P46581 Neurogenic differentiation factor 1; NeuroD from Caenorhabditis elegans (see 3 papers)
NP_001379767 Neurogenic differentiation factor 1 from Caenorhabditis elegans
44% identity, 28% coverage

• function: Acts as a transcriptional regulator whose activity is required for several aspects of motor neuron fate specification, including cell division patterns, proper spatiotemporal expression of fate-specific markers, and normal axonal morphology and pathfinding (PubMed:10976055). Involved in regulating glial specification (PubMed:32665354).
  disruption phenotype: Defects in axonal morphology and synaptic connectivity of the ventral cord motor neurons.
• cnd-1/NeuroD1 Functions with the Homeobox Gene ceh-5/Vax2 and Hox Gene ceh-13/labial To Specify Aspects of RME and DD Neuron Fate in Caenorhabditis elegans.
  Aquino-Nunez, G3 (Bethesda, Md.) 2020
  • GeneRIF: cnd-1/NeuroD1 Functions with the Homeobox Gene ceh-5/Vax2 and Hox Gene ceh-13/labial To Specify Aspects of RME and DD Neuron Fate in Caenorhabditis elegans.

HND1_CAEEL / Q18612 Hand transcription factor 1 from Caenorhabditis elegans (see 3 papers)
NP_509952 Hand transcription factor 1 from Caenorhabditis elegans
37% identity, 36% coverage

• function: Probable transcription factor which regulates early embryonic myogenesis, in cooperation with transcription factors unc-120 and hlh-1 (PubMed:15892873, PubMed:17142668). Involved in controlling the number and position of somatic gonadal precursor cells (SGPs) in the gonadal primordium, and embryonic body shape (PubMed:12756172).
  disruption phenotype: Adults are viable and fertile, but with a moderate frequency of somatic gonad defects, which increases on an ehn- 3 mutant background (PubMed:12756172). Low frequency of embryonic lethality, with embryos arresting paralyzed at the two-fold stage; increases in frequency significantly on an hlh-1 or unc-120 mutant background (PubMed:12756172, PubMed:15892873, PubMed:17142668). Many embryos that survive to hatch become uncoordinated, dumpy larvae with variable body shape defects, typically in the posterior (PubMed:12756172, PubMed:15892873). One quarter of the embryos from homozygous hnd-1;hlh-1 heterozygous parents exhibit reduced expression of myosin myo-3 (PubMed:17142668). On a unc-120 mutant background, progeny show reduced expression of myo-3 at mid-embryogenesis (PubMed:17142668). RNAi-mediated knockdown results in abnormal number and positioning of the somatic gonadal precursor cells (SGPs) and influences the maintenance of primordial germ cells (PGCs) in L1 larvae (PubMed:15892873).
• Defining the transcriptional redundancy of early bodywall muscle development in C. elegans: evidence for a unified theory of animal muscle development.
  Fukushige, Genes & development 2006
  • GeneRIF: findings show that in addition to HLH-1, UNC-120/SRF and HND-1/HAND, can convert naive blastomeres to muscle when overproduced ectopically in the embryo; both of these factors act in concert with HLH-1 to regulate myogenesis
• The C. elegans Hand gene controls embryogenesis and early gonadogenesis.
  Mathies, Development (Cambridge, England) 2003 (PubMed)
  • GeneRIF: affects the presence and position of both the somatic gonadal precursors and primordial germ cells within the primordium, but does not appear to have any role in later gonadogenesis

XP_696212 basic helix-loop-helix transcription factor scleraxis from Danio rerio
37% identity, 34% coverage

• Scleraxis genes are required for normal musculoskeletal development and for rib growth and mineralization in zebrafish.
  Kague, FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2019
  • GeneRIF: Although scxb mutants show no obvious phenotype, scxa mutant embryos have defects in cranial tendon maturation and muscle misalignment. Mutation of both scleraxis genes results in more severe defects in cranial tendon differentiation, muscle and cartilage dysmorphogenesis and paralysis, and lethality by 2-5 wk, which indicates an essential function of scleraxis for craniofacial development.

ASCL2_BOVIN / Q2EGB9 Achaete-scute homolog 2; Mash2 from Bos taurus (Bovine) (see paper)
53% identity, 23% coverage

• function: Transcription factor. Binds to E-box motifs 5'-CANNTG-3' in the regulatory elements of target genes, probably as a heterodimer with another basic helix-loop-helix (bHLH) protein such as the transcription factor TCF3. May bind both open and closed chromatin, acting as a pioneer transcription factor to allow other factors to bind and activate lineage-specific genes. Required during post-implantation development for the generation of some differentiated trophoblast cell types. Transcriptional activity of ASCL2 may be antagonised in a subset of trophoblast cells by bHLH transcription factor HAND1, perhaps by competing for dimerization with other bHLH proteins. Involved in differentiation and function of follicular T-helper (Tfh) cells, thereby playing a role in germinal center responses; probably modulates expression of genes involved in Tfh cell function, such as BCL6. May also act as a suppressor of Th1-, Th2- and Th17-cell differentiation. Induces the formation of stem cells in intestinal crypts in vitro, synergistically activating transcription of target genes, such as SOX9, together with TCF4/beta-catenin. May form a bistable transcriptional switch, controlling expression of its own gene together with Wnt/R- spondin signaling, and thereby maintaining stem cell characteristics (By similarity). Modulates expression of target genes, including perhaps down-regulating EGR1/Krox24 and chemokine CXCL10/Mob-1 and up- regulating CXCR4 and CDKN1C/p57kip2, in Schwann cells. May play a role in reducing proliferation of Schwann cells, perhaps acting via modulation of expression of CDKN1C (By similarity). May be dispensable for blastocyst formation and later embryonic function (By similarity). May be involved in the determination of neuronal precursors (By similarity).
  subunit: Efficient DNA binding requires dimerization with another basic helix-loop-helix (bHLH) protein. Forms heterodimers with bHLH transcription factor TCF3. May not heterodimerise with bHLH protein HAND1.

NP_001035697 achaete-scute homolog 2 from Bos taurus
53% identity, 23% coverage

• The Molecular Characteristics of the FAM13A Gene and the Role of Transcription Factors ACSL1 and ASCL2 in Its Core Promoter Region.
  Liang, Genes 2019
  • GeneRIF: Results indicate that ASCL2 transcription factor binds to the core promoter region of FAM13A and positively regulates its transcription.
• Identification of abnormal gene expression in bovine transgenic somatic cell nuclear transfer embryos.
  Cho, Journal of veterinary science 2014
  • GeneRIF: More DNMT1 mRNA was detected in the transgenic somatic cell nuclear transfer (SCNT) group than the other three groups. Hsp 70.1 mRNA was detected in the in vitro fertilzation embryos. Mash2 mRNA was present at highest levels in transgenic SCNT embryos.
• Characterization of the placenta specific bovine mammalian achaete scute-like homologue 2 (Mash2) gene.
  Arnold, Placenta (PubMed)
  • GeneRIF: Mash2 is highly conserved across species and is specifically expressed in the bovine placenta. Bovine Mash2 appears to be maternally expressed after implantation, but the paternal genome plays a role in regulating expression.

P09774 Achaete-scute complex protein T3 from Drosophila melanogaster
NP_476623 lethal of scute from Drosophila melanogaster
41% identity, 23% coverage

• HFR1 encodes an atypical bHLH protein that acts in phytochrome A signal transduction.
  Fairchild, Genes & development 2000
• Dual role for Drosophila lethal of scute in CNS midline precursor formation and dopaminergic neuron and motoneuron cell fate.
  Stagg, Development (Cambridge, England) 2011
  • GeneRIF: lethal of scute regulates mVUM motoneuron gene expression and is required for the formation of MP4-6 and the MNB. It controls l(1)sc plays an important regulatory role in both neurogenesis and specifying dopaminergic neuron and motoneuron identities

ASCL2_HUMAN / Q99929 Achaete-scute homolog 2; ASH-2; hASH2; Class A basic helix-loop-helix protein 45; bHLHa45; Mash2 from Homo sapiens (Human) (see 4 papers)
NP_005161 achaete-scute homolog 2 from Homo sapiens
53% identity, 23% coverage

• function: Transcription factor. Binds to E-box motifs 5'-CANNTG-3' in the regulatory elements of target genes, probably as a heterodimer with another basic helix-loop-helix (bHLH) protein such as the transcription factor TCF3. May bind both open and closed chromatin, acting as a pioneer transcription factor to allow other factors to bind and activate lineage-specific genes. Required during post-implantation development for the generation of some differentiated trophoblast cell types. Transcriptional activity of ASCL2 may be antagonised in a subset of trophoblast cells by bHLH transcription factor HAND1, perhaps by competing for dimerization with other bHLH proteins. Involved in differentiation and function of follicular T-helper (Tfh) cells, thereby playing a role in germinal center responses; probably modulates expression of genes involved in Tfh cell function, such as BCL6. May also act as a suppressor of Th1-, Th2- and Th17-cell differentiation. Induces the formation of stem cells in intestinal crypts in vitro, synergistically activating transcription of target genes, such as SOX9, together with TCF4/beta-catenin. May form a bistable transcriptional switch, controlling expression of its own gene together with Wnt/R- spondin signaling, and thereby maintaining stem cell characteristics (By similarity). Modulates expression of target genes, including perhaps down-regulating EGR1/Krox24 and chemokine CXCL10/Mob-1 and up- regulating CXCR4 and CDKN1C/p57kip2, in Schwann cells. May play a role in reducing proliferation of Schwann cells, perhaps acting via modulation of expression of CDKN1C (By similarity). May be dispensable for blastocyst formation and later embryonic function (By similarity). May be involved in the determination of neuronal precursors (By similarity).
  subunit: Efficient DNA binding requires dimerization with another basic helix-loop-helix (bHLH) protein. Forms heterodimers with bHLH transcription factor TCF3. May not heterodimerise with bHLH protein HAND1.
• TET2-BCLAF1 transcription repression complex epigenetically regulates the expression of colorectal cancer gene Ascl2 via methylation of its promoter.
  Shang, The Journal of biological chemistry 2022
  • GeneRIF: TET2-BCLAF1 transcription repression complex epigenetically regulates the expression of colorectal cancer gene Ascl2 via methylation of its promoter.
• ASCL2 Affects the Efficacy of Immunotherapy in Colon Adenocarcinoma Based on Single-Cell RNA Sequencing Analysis.
  Wu, Frontiers in immunology 2022
  • GeneRIF: ASCL2 Affects the Efficacy of Immunotherapy in Colon Adenocarcinoma Based on Single-Cell RNA Sequencing Analysis.
• Achaete-scute complex-like 2 regulated inflammatory mechanism through Toll-like receptor 4 activating in stomach adenocarcinoma.
  Zheng, World journal of surgical oncology 2022
  • GeneRIF: Achaete-scute complex-like 2 regulated inflammatory mechanism through Toll-like receptor 4 activating in stomach adenocarcinoma.
• Potential Mechanism of Immune Evasion Associated with the Master Regulator ASCL2 in Microsatellite Stability in Colorectal Cancer.
  Yang, Journal of immunology research 2021
  • GeneRIF: Potential Mechanism of Immune Evasion Associated with the Master Regulator ASCL2 in Microsatellite Stability in Colorectal Cancer.
• ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development.
  Varberg, Proceedings of the National Academy of Sciences of the United States of America 2021
  • GeneRIF: ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development.
• Comprehensive Genetic Search to Clarify the Molecular Mechanism of Drug Resistance Identifies ASCL2-LEF1/TSPAN8 Axis in Colorectal Cancer.
  Tanaka, Annals of surgical oncology 2019 (PubMed)
  • GeneRIF: High ASCL2 expression is associated with Drug Resistance in Colorectal Cancer.
• Ascl2 facilitates IL-10 production in Th17 cells to restrain their pathogenicity in inflammatory bowel disease.
  Yi, Biochemical and biophysical research communications 2019 (PubMed)
  • GeneRIF: Ascl2 negatively modulates pathogenic Th17cell differentiation via promoting IL-10 production, and alleviates intestinal inflammation.
• WiNTRLINC1/ASCL2/c-Myc Axis Characteristics of Colon Cancer with Differentiated Histology at Young Onset and Essential for Cell Viability.
  Yokota, Annals of surgical oncology 2019 (PubMed)
  • GeneRIF: High ASCL2 expression is associated with colon cancer.
• More
• Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq.
  Kingsley, Genes 2019
  • “...Q9BXK1 Heart 1 MZF1 BGGGGA 2.23 10 5 P28698 2 Ascl2 ARCAGCTGCY 7.06 10 4 Q99929 3 ASCL1 VSAGCAGCTGSNN 9.41 10 4 P50553 4 SP3 VCCACGCCCMC 1.42 10 3 Q02447 5 NEUROD1 NRACAGATGGYNN 1.60 10 3 Q13562 Lamina 1 SP2 GYCCCGCCYCYBSSS 8.51 10 15 Q02086 2...”
• Phylogenetic analysis of the human basic helix-loop-helix proteins
  Ledent, Genome biology 2002
  • “...Gene name Family Mouse ortholog(s) Contigs Chromosome localization P50553 Hash1 Achaete-Scute a Mash1 NT_009439.3 12q22-q23 Q99929 Hash2 Achaete-Scute a Mash2 NT_009368.3 11p15.5 N024228 Hash3a * Achaete-Scute b Mash3 NT_024228.3 11p15.3 N004680 Hash3b * Achaete-Scute b ? NT_004680.3 1q31-q32 N009720 Hash3c * Achaete-Scute b ? NT_009720.3 12q23-q24...”
  • “...Gene name Family Human ortholog(s) Accession number Mash1 Achaete-Scute a P50553 gb|AAB28830.1 Mash2 Achaete-Scute a Q99929 gb|AAD33794.1 Mash3 Achaete-Scute b N024228 sp|CAC37689 Myogenin MyoD P15173 sp|P12979 Myf6 MyoD P23409 ref|NP_032683.1 MyoD MyoD P15172 sp|P10085 Myf5 MyoD P13349 ref|NP_032682.1 E2A E12/E47 N011269 sp|15806 TF12 E12/E47 Q99081 ref|NP_035674.1...”

NP_001163702 nautilus, isoform B from Drosophila melanogaster
39% identity, 21% coverage

• Combinatorial coding of Drosophila muscle shape by Collier and Nautilus.
  Enriquez, Developmental biology 2012 (PubMed)
  • GeneRIF: Data show that the three dorso-lateral (DL) progenitors which express Nautilus and Collier are specified in a fixed temporal sequence and that each expresses additionally other, distinct identity transcription factors (iTFs).
• Stereotypic founder cell patterning and embryonic muscle formation in Drosophila require nautilus (MyoD) gene function.
  Wei, Proceedings of the National Academy of Sciences of the United States of America 2007
  • GeneRIF: nautilus gene activity is required to seed the correct founder myoblast pattern that prefigures the muscle fiber arrangement during embryonic development

MYOD_DROME / P22816 Myogenic-determination protein; Protein nautilus; dMyd from Drosophila melanogaster (Fruit fly) (see 2 papers)
39% identity, 21% coverage

• function: May play an important role in the early development of muscle.
  subunit: Efficient DNA binding requires dimerization with another bHLH protein

APG_ORYSJ / Q6AT90 Transcription factor APG; Basic helix-loop-helix protein 106; OsbHLH106; Protein ANTAGONIST OF PGL1; bHLH transcription factor bHLH106 from Oryza sativa subsp. japonica (Rice) (see paper)
37% identity, 14% coverage

• function: Atypical bHLH transcription factor that acts as a negative regulator of grain size. Binds the transcription factor ILI6 and forms a heterodimer of antagonistic bHLH transcription factors that regulates grain length and weight by controlling cell elongation in lemma and palea. May be involved in the control of lamina inclination through brassinosteroid signaling pathway.
  subunit: Homodimer and heterodimer with ILI5 or ILI6
• Generation of High Yielding and Fragrant Rice (Oryza sativa L.) Lines by CRISPR/Cas9 Targeted Mutagenesis of Three Homoeologs of Cytochrome P450 Gene Family and OsBADH2 and Transcriptome and Proteome Profiling of Revealed Changes Triggered by Mutations
  Usman, Plants (Basel, Switzerland) 2020
  • “...2), Q6YYV8 (BAHD acyltransferase-like protein gene) and B9F4Q9 (E3 ubiquitin-protein ligase GW2) were upregulated while Q6AT90 (transcription factor APG) was downregulated in GXU7-1. Three DEPs including Q0J4I1 (cyclin-dependent kinase B2-1), Q6YXH8 (cyclin-D4-1), and P29618 (cyclin-dependent kinase A-1) controlling cell cycle and division were found to be...”
  • “...(BAHD acyltransferase-like protein gene; SLG), and two downregulated DEPs including B9F4Q9 (E3 ubiquitin-protein ligase;GW2), and Q6AT90 (Transcription factor APG;APG) related to grain size and development. PGL2 is a typical bHLH proteins gene that positively regulates the rice grain length by increasing the cell length of the...”

BHA15_HUMAN / Q7RTS1 Class A basic helix-loop-helix protein 15; bHLHa15; Class B basic helix-loop-helix protein 8; bHLHb8; Muscle, intestine and stomach expression 1; MIST-1 from Homo sapiens (Human) (see paper)
NP_803238 class A basic helix-loop-helix protein 15 from Homo sapiens
42% identity, 34% coverage

• function: Plays a role in controlling the transcriptional activity of MYOD1, ensuring that expanding myoblast populations remain undifferentiated. Repression may occur through muscle-specific E-box occupancy by homodimers. May also negatively regulate bHLH-mediated transcription through an N-terminal repressor domain. Serves as a key regulator of acinar cell function, stability, and identity. Also required for normal organelle localization in exocrine cells and for mitochondrial calcium ion transport. May function as a unique regulator of gene expression in several different embryonic and postnatal cell lineages. Binds to the E-box consensus sequence 5'-CANNTG-3' (By similarity).
  subunit: Forms homodimers or heterodimers with TCF3 gene products E12 and E47. These dimers bind to the E-box site, however, heterodimer with MYOD1 does not bind target DNA (By similarity).
• Splicing factor 2-associated protein p32 participates in ribosome biogenesis by regulating the binding of Nop52 and fibrillarin to preribosome particles
  Yoshikawa, Molecular & cellular proteomics : MCP 2011
  • “...P05412 P51532 Q14498 Q8N7H5 P30876 P15336 Q7RTS1 YY1-associated protein 1 Transcriptional repressor p66-beta Transcription intermediary factor 1-beta...”
• DDX56 transcriptionally activates MIST1 to facilitate tumorigenesis of HCC through PTEN-AKT signaling.
  Zhou, Theranostics 2022
  • GeneRIF: DDX56 transcriptionally activates MIST1 to facilitate tumorigenesis of HCC through PTEN-AKT signaling.
• Diffuse MIST1 expression and decreased α1,4-linked N-acetylglucosamine (αGlcNAc) glycosylation on MUC6 are distinct hallmarks for gastric neoplasms showing oxyntic gland differentiation.
  Yamada, Histopathology 2020 (PubMed)
  • GeneRIF: Diffuse MIST1 expression and decreased alpha1,4-linked N-acetylglucosamine (alphaGlcNAc) glycosylation on MUC6 are distinct hallmarks for gastric neoplasms showing oxyntic gland differentiation.
• Clinical Significance of Tumour CD44v and MIST1 Expression in Patients With Non-small-cell Lung Cancer.
  Nagashima, Anticancer research 2020 (PubMed)
  • GeneRIF: Clinical Significance of Tumour CD44v and MIST1 Expression in Patients With Non-small-cell Lung Cancer.
• MIST1, an Inductive Signal for Salivary Amylase in Mesenchymal Stem Cells.
  Mona, International journal of molecular sciences 2019
  • GeneRIF: Overexpression of MIST1-induced AMY1 expression while it had little effect on CK19 expression.
• Mist1: a novel nuclear marker for acinic cell carcinoma of the salivary gland.
  Hsieh, Virchows Archiv : an international journal of pathology 2019 (PubMed)
  • GeneRIF: Mist1 is a sensitive marker for serous acinar cells of salivary glands and acinic cell carcinoma (AciCC), and background non-tumour acinar cells and plasma cells can serve as good internal positive controls.
• Expression of LGR5, FZD7, TROY, and MIST1 in Perioperatively Treated Gastric Carcinomas and Correlation with Therapy Response.
  Freiin, Disease markers 2019
  • GeneRIF: High MIST1 expression is associated with lymph node metastasis in Gastric cancer.
• Overexpression of MIST1 reverses the epithelial-mesenchymal transition and reduces the tumorigenicity of pancreatic cancer cells via the Snail/E-cadherin pathway.
  Li, Cancer letters 2018 (PubMed)
  • GeneRIF: restoring the expression of MIST1 reverses the EMT and reduces the tumorigenicity of pancreatic cancer cells partly via the Snail/E-cadherin pathway
• Activation of protein kinase Cδ leads to increased pancreatic acinar cell dedifferentiation in the absence of MIST1.
  Johnson, The Journal of pathology 2012 (PubMed)
  • GeneRIF: Activation of protein kinase Cdelta leads to increased pancreatic acinar cell dedifferentiation in the absence of MIST1.
• More

NP_571166 protein atonal homolog 1a from Danio rerio
41% identity, 24% coverage

• The interplay of atoh1 genes in the lower rhombic lip during hindbrain morphogenesis.
  Belzunce, PloS one 2020
  • GeneRIF: interplay of atoh1 genes in the lower rhombic lip during hindbrain morphogenesis
• Fgf-signaling-dependent Sox9a and Atoh1a regulate otic neural development in zebrafish.
  Wang, The Journal of neuroscience : the official journal of the Society for Neuroscience 2015
  • GeneRIF: A genetic network of sensory determinant, Atoh1 (and Sox9a), play critical roles in otic neural development.
• Sox2 and Fgf interact with Atoh1 to promote sensory competence throughout the zebrafish inner ear.
  Sweet, Developmental biology 2011
  • GeneRIF: Sox2 and Fgf interact with Atoh1 to promote sensory competence throughout the zebrafish inner ear.
• Atoh1a expression must be restricted by Notch signaling for effective morphogenesis of the posterior lateral line primordium in zebrafish.
  Matsuda, Development (Cambridge, England) 2010
  • GeneRIF: Atoh1a expression must be restricted by Notch signaling for effective morphogenesis of the posterior lateral line primordium in zebrafish.
• Zebrafish atoh1 genes: classic proneural activity in the inner ear and regulation by Fgf and Notch.
  Millimaki, Development (Cambridge, England) 2007 (PubMed)
  • GeneRIF: atoh1a and atoh1b are together necessary for hair cell development. These genes crossregulate each other but are differentially required during distinct developmental periods
• Proneural gene requirement for hair cell differentiation in the zebrafish lateral line.
  Sarrazin, Developmental biology 2006 (PubMed)
  • GeneRIF: in the zebrafish, two proneural genes are essential for differentiation of the hair cells, neuroD and atonal homolog 1

XP_425989 fer3-like protein from Gallus gallus
40% identity, 37% coverage

• Nato3 plays an integral role in dorsoventral patterning of the spinal cord by segregating floor plate/p3 fates via Nkx2.2 suppression and Foxa2 maintenance.
  Mansour, Development (Cambridge, England) 2014 (PubMed)
  • GeneRIF: Nato3 induces ectopic Foxa2-positive cells and indirectly downregulates Nkx2.2 expression.

NP_001071120 class A basic helix-loop-helix protein 15 from Danio rerio
45% identity, 32% coverage

• Cloning, expression, and functional characterization of zebrafish Mist1.
  Guo, Biochemical and biophysical research communications 2007 (PubMed)
  • GeneRIF: These results suggest that Mist1 functions in an evolutionary conserved way as a key transcriptional regulator specific for exocrine pancreas development in zebrafish.

NP_001025534 myogenic factor 5 from Gallus gallus
42% identity, 25% coverage

• Expression profiles and association analysis with growth traits of the MyoG and Myf5 genes in the Jinghai yellow chicken.
  Genxi, Molecular biology reports 2014 (PubMed)
  • GeneRIF: Single nucleotide polymorphisms of the MyoG and Myf5 genes had certain effects on growth traits of the Jinghai yellow chicken.
• A distinct profile of myogenic regulatory factor detection within Pax7+ cells at S phase supports a unique role of Myf5 during posthatch chicken myogenesis.
  Day, Developmental dynamics : an official publication of the American Association of Anatomists 2009
  • GeneRIF: Myf5 was detected strictly within Pax7(+) cells and decreased during S phase while MyoD presence persisted in cycling cells
• Klhl31 is associated with skeletal myogenesis and its expression is regulated by myogenic signals and Myf-5.
  Abou-Elhamd, Mechanisms of development 2009 (PubMed)
  • GeneRIF: ectopic expression of Myf-5 led to expression of Klhl31 in the developing neural tube, indicating that Klhl31 is a novel and integral part of vertebrate myogenesis

NP_033343 T-cell acute lymphocytic leukemia protein 2 homolog from Mus musculus
51% identity, 49% coverage

• Expression and Regulation of Tal2 during Neuronal Differentiation in P19 Cells.
  Kobayashi, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 2017 (PubMed)
  • GeneRIF: It is induced during neural differentiation in P19 cells, which are pluripotent mouse embryonal carcinoma cells that differentiate into the neural lineage upon both exposure to all-trans retinoic acid (atRA) and the formation of cell aggregation.
• The T-cell oncogene Tal2 Is a Target of PU.1 and upregulated during osteoclastogenesis.
  Courtial, PloS one 2013
  • GeneRIF: the expression control of Tal2 in hematopoietic cells

XP_021183890 achaete-scute complex protein T3 from Helicoverpa armigera
43% identity, 23% coverage

• Cloning of Wing-Development-Related Genes and mRNA Expression Under Heat Stress in Chlorpyrifos-Resistant and -Susceptible Plutella xylostella
  Chen, Scientific reports 2018
  • “...78, 79, 79 and 81 percent with Bombyx mori (NP_001037416), Danaus plexippus (OWR43025), Helicoverpa armigera (XP_021183890) and Spodoptera litura (XP_022829400.1), respectively (Fig. S1 ). ash2 had exhibited 85, 84 and 83 percent with B . mori (NP_001098692), S . litura (XP_022829477), and H . armigera (XP_021183904),...”

NP_001037416 achaete-scute-like protein from Bombyx mori
43% identity, 23% coverage

• Cloning of Wing-Development-Related Genes and mRNA Expression Under Heat Stress in Chlorpyrifos-Resistant and -Susceptible Plutella xylostella
  Chen, Scientific reports 2018
  • “...Aedes aegypti ASC (XP_021712495.1); Plutella xylostella ASH1 (AIZ67914.1); Danaus plexippus ASH1 (OWR43025.1); Bombyx mori ASH1 (NP_001037416.1); Pieris rapae ASC (XP_022115666.1); Bombyx mori ASH2 (NP_001098692.1); Operophtera brumata ASH2 (KOB67667.1); Plutella xylostella ASH2 (AIZ67913.1); Bombyx mori ASH3 (NP_001098694.1); Plutella xylostella ASH3 (ALC76152.1); Danaus plexippus ASH3 (OWR43023.1); Operophtera brumata...”
  • “...were as follows. ash1 had presented 78, 79, 79 and 81 percent with Bombyx mori (NP_001037416), Danaus plexippus (OWR43025), Helicoverpa armigera (XP_021183890) and Spodoptera litura (XP_022829400.1), respectively (Fig. S1 ). ash2 had exhibited 85, 84 and 83 percent with B . mori (NP_001098692), S . litura...”
• Analysis of four achaete-scute homologs in Bombyx mori reveals new viewpoints of the evolution and functions of this gene family
  Zhou, BMC genetics 2008
  • “...coenia ) Achaete-Scute homolog 1 (Genbank: AAC24714 ); Bm-ASH1, Bombyx mori Achaete-Scute homolog 1 (Genbank: NP_001037416 ); Bm-ASH2, Bombyx mori Achaete-Scute homolog 2 (Genbank: EF620927 ); Bm-ASH3, Bombyx mori Achaete-Scute homolog 3 (Genbank: EF620928 ); Cn-ASH, Hydra vulgaris cnidarian Achaete-Scute homolog (Genbank: U36275 ); Cs-ASH1, Cupiennius...”

New Search

Statistics

How It Works

PaperBLAST builds a database of protein sequences that are linked to scientific articles. These links come from automated text searches against the articles in EuropePMC and from manually-curated information from GeneRIF, UniProtKB/Swiss-Prot, BRENDA, CAZy (as made available by dbCAN), BioLiP, CharProtDB, MetaCyc, EcoCyc, TCDB, REBASE, the Fitness Browser, and a subset of the European Nucleotide Archive with the /experiment tag. Given this database and a protein sequence query, PaperBLAST uses protein-protein BLAST to find similar sequences with E < 0.001.

To build the database, we query EuropePMC with locus tags, with RefSeq protein identifiers, and with UniProt accessions. We obtain the locus tags from RefSeq or from MicrobesOnline. We use queries of the form "locus_tag AND genus_name" to try to ensure that the paper is actually discussing that gene. Because EuropePMC indexes most recent biomedical papers, even if they are not open access, some of the links may be to papers that you cannot read or that our computers cannot read. We query each of these identifiers that appears in the open access part of EuropePMC, as well as every locus tag that appears in the 500 most-referenced genomes, so that a gene may appear in the PaperBLAST results even though none of the papers that mention it are open access. We also incorporate text-mined links from EuropePMC that link open access articles to UniProt or RefSeq identifiers. (This yields some additional links because EuropePMC uses different heuristics for their text mining than we do.)

For every article that mentions a locus tag, a RefSeq protein identifier, or a UniProt accession, we try to select one or two snippets of text that refer to the protein. If we cannot get access to the full text, we try to select a snippet from the abstract, but unfortunately, unique identifiers such as locus tags are rarely provided in abstracts.

PaperBLAST also incorporates manually-curated protein functions:

• Proteins from NCBI's RefSeq are included if a GeneRIF entry links the gene to an article in PubMed^®. GeneRIF also provides a short summary of the article's claim about the protein, which is shown instead of a snippet.
• Proteins from Swiss-Prot (the curated part of UniProt) are included if the curators identified experimental evidence for the protein's function (evidence code ECO:0000269). For these proteins, the fields of the Swiss-Prot entry that describe the protein's function are shown (with bold headings).
• Proteins from BRENDA, a curated database of enzymes, are included if they are linked to a paper in PubMed and their full sequence is known.
• Every protein from the non-redundant subset of BioLiP, a database of ligand-binding sites and catalytic residues in protein structures, is included. Since BioLiP itself does not include descriptions of the proteins, those are taken from the Protein Data Bank. Descriptions from PDB rely on the original submitter of the structure and cannot be updated by others, so they may be less reliable. (For SitesBLAST and Sites on a Tree, we use a larger subset of BioLiP so that every ligand is represented among a group of structures with similar sequences, but for PaperBLAST, we use the non-redundant set provided by BioLiP.)
• Every protein from EcoCyc, a curated database of the proteins in Escherichia coli K-12, is included, regardless of whether they are characterized or not.
• Proteins from the MetaCyc metabolic pathway database are included if they are linked to a paper in PubMed and their full sequence is known.
• Proteins from the Transport Classification Database (TCDB) are included if they have known substrate(s), have reference(s), and are not described as uncharacterized or putative. (Some of the references are not visible on the PaperBLAST web site.)
• Every protein from CharProtDB, a database of experimentally characterized protein annotations, is included.
• Proteins from the CAZy database of carbohydrate-active enzymes are included if they are associated with an Enzyme Classification number. Even though CAZy does not provide links from individual protein sequences to papers, these should all be experimentally-characterized proteins.
• Proteins from the REBASE database of restriction enzymes are included if they have known specificity.
• Every protein with an evidence-based reannotation (based on mutant phenotypes) in the Fitness Browser is included.
• Sequence-specific transcription factors (including sigma factors and DNA-binding response regulators) with experimentally-determined DNA binding sites from the PRODORIC database of gene regulation in prokaryotes.
• Putative transcription factors from RegPrecise that have manually-curated predictions for their binding sites. These predictions are based on conserved putative regulatory sites across genomes that contain similar transcription factors, so PaperBLAST clusters the TFs at 70% identity and retains just one member of each cluster.
• Coding sequence (CDS) features from the European Nucleotide Archive (ENA) are included if the /experiment tag is set (implying that there is experimental evidence for the annotation), the nucleotide entry links to paper(s) in PubMed, and the nucleotide entry is from the STD data class (implying that these are targeted annotated sequences, not from shotgun sequencing). Also, to filter out genes whose transcription or translation was detected, but whose function was not studied, nucleotide entries or papers with more than 25 such proteins are excluded. Descriptions from ENA rely on the original submitter of the sequence and cannot be updated by others, so they may be less reliable.

Except for GeneRIF and ENA, the curated entries include a short curated description of the protein's function. For entries from BioLiP, the protein's function may not be known beyond binding to the ligand. Many of these entries also link to articles in PubMed.

For more information see the PaperBLAST paper (mSystems 2017) or the code. You can download PaperBLAST's database here.

Changes to PaperBLAST since the paper was written:

• November 2023: incorporated PRODORIC and RegPrecise. Many PRODORIC entries were not linked to a protein sequence (no UniProt identifier), so we added this information.
• February 2023: BioLiP changed their download format. PaperBLAST now includes their non-redundant subset. SitesBLAST and Sites on a Tree use a larger non-redundant subset that ensures that every ligand is represented within each cluster. This should ensure that every binding site is represented.
• June 2022: incorporated some coding sequences from ENA with the /experiment tag.
• March 2022: incorporated BioLiP.
• April 2020: incorporated TCDB.
• April 2019: EuropePMC now returns table entries in their search results. This has expanded PaperBLAST's database, but most of the new entries are of low relevance, and the resulting snippets are often just lists of locus tags with annotations.
• February 2018: the alignment page reports the conservation of the hit's functional sites (if available from from Swiss-Prot or UniProt)
• January 2018: incorporated BRENDA.
• December 2017: incorporated MetaCyc, CharProtDB, CAZy, REBASE, and the reannotations from the Fitness Browser.
• September 2017: EuropePMC no longer returns some table entries in their search results. This has shrunk PaperBLAST's database, but has also reduced the number of low-relevance hits.

Many of these changes are described in Interactive tools for functional annotation of bacterial genomes.

Secrets

PaperBLAST cannot provide snippets for many of the papers that are published in non-open-access journals. This limitation applies even if the paper is marked as "free" on the publisher's web site and is available in PubmedCentral or EuropePMC. If a journal that you publish in is marked as "secret," please consider publishing elsewhere.

Omissions from the PaperBLAST Database

Many important articles are missing from PaperBLAST, either because the article's full text is not in EuropePMC (as for many older articles), or because the paper does not mention a protein identifier such as a locus tag, or because of PaperBLAST's heuristics. If you notice an article that characterizes a protein's function but is missing from PaperBLAST, please notify the curators at UniProt or add an entry to GeneRIF. Entries in either of these databases will eventually be incorporated into PaperBLAST. Note that to add an entry to UniProt, you will need to find the UniProt identifier for the protein. If the protein is not already in UniProt, you can ask them to create an entry. To add an entry to GeneRIF, you will need an NCBI Gene identifier, but unfortunately many prokaryotic proteins in RefSeq do not have corresponding Gene identifers.

References

PaperBLAST: Text-mining papers for information about homologs.
M. N. Price and A. P. Arkin (2017). mSystems, 10.1128/mSystems.00039-17.

Europe PMC in 2017.
M. Levchenko et al (2017). Nucleic Acids Research, 10.1093/nar/gkx1005.

Gene indexing: characterization and analysis of NLM's GeneRIFs.
J. A. Mitchell et al (2003). AMIA Annu Symp Proc 2003:460-464.

UniProt: the universal protein knowledgebase.
The UniProt Consortium (2016). Nucleic Acids Research, 10.1093/nar/gkw1099.

BRENDA in 2017: new perspectives and new tools in BRENDA.
S. Placzek et al (2017). Nucleic Acids Research, 10.1093/nar/gkw952.

The EcoCyc database: reflecting new knowledge about Escherichia coli K-12.
I. M. Keeseler et al (2016). Nucleic Acids Research, 10.1093/nar/gkw1003.

The MetaCyc database of metabolic pathways and enzymes.
R. Caspi et al (2018). Nucleic Acids Research, 10.1093/nar/gkx935.

CharProtDB: a database of experimentally characterized protein annotations.
R. Madupu et al (2012). Nucleic Acids Research, 10.1093/nar/gkr1133.

The carbohydrate-active enzymes database (CAZy) in 2013.
V. Lombard et al (2014). Nucleic Acids Research, 10.1093/nar/gkt1178.

The Transporter Classification Database (TCDB): recent advances
M. H. Saier, Jr. et al (2016). Nucleic Acids Research, 10.1093/nar/gkv1103.

REBASE - a database for DNA restriction and modification: enzymes, genes and genomes.
R. J. Roberts et al (2015). Nucleic Acids Research, 10.1093/nar/gku1046.

Deep annotation of protein function across diverse bacteria from mutant phenotypes.
M. N. Price et al (2016). bioRxiv, 10.1101/072470.