Family Search for PF10176 (NEDD4_Bsd2)

This website will be down from the evening of March 29 (CA time) through March 30

Running HMMer for PF10176

PF10176 hits 13 sequences in PaperBLAST's database above the trusted cutoff. Showing all hits. Or show only hits to curated sequences or try another family.

AFUA_4G13740 metal homeostatis protein bsd2 from Aspergillus fumigatus Af293
Aligns to 288:426 / 446 (31.2%), covers 100.0% of PF10176, 167.2 bits

• Conservation of nucleosome positions in duplicated and orthologous gene pairs
  Nishida, TheScientificWorldJournal 2012
  • “...AFUA_4G06790 0.185927497 YDR062W AFUA_6G00300 0.189190157 YOL086C AFUA_7G01010 0.190813468 YOL026C AFUA_5G03630 0.19138562 YIL033C AFUA_3G10000 0.195925157 YBR290W AFUA_4G13740 0.19955841 YAR019C AFUA_4G06750 0.204744755 YHL007C AFUA_2G04680 0.20737573 YMR078C AFUA_7G05480 0.222707833 YDR311W AFUA_4G11690 0.22686955 YOL100W AFUA_3G12670 0.230714484 YGR162W AFUA_2G09490 0.232235851 YGL255W AFUA_1G01550 0.248116851 YPL038W AFUA_6G01910 0.252388553 YCL035C AFUA_1G06100 0.255759517 YNL082W AFUA_2G13410...”

BSD2_YEAST / P38356 Metal homeostatis protein BSD2; Bypass SOD defects protein 2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) (see 4 papers)
YBR290W Bsd2p from Saccharomyces cerevisiae
NP_009849 Bsd2p from Saccharomyces cerevisiae S288C
Aligns to 171:316 / 321 (45.5%), covers 99.2% of PF10176, 154.6 bits

• function: Required for homeostasis of heavy metal ions such as cadmium, cobalt and copper. Controls metal ion transport and prevents metal hyperaccumulation by negatively regulating the SMF1 and SMF2 metal transport systems. Under manganese-replete conditions facilitates trafficking of SMF1 and SMF2 metal transporters to the vacuole where they are degraded.
  disruption phenotype: Increased accumulation of copper, cadmium and cobalt ions and enhanced sensitivity to the toxic effects of copper and cadmium. Exhibits no additional sensitivity to manganese. SMF1 fails to enter the vacuole and is stabilized. Reverses the aerobic defects of yeast strains lacking superoxide dismutase (SOD). Concomitant deletion of SMF1 completely abolishes the ability of BSD2 deletion to suppress SOD deficiency and reverses the increased sensitivity to cadmium and copper. However cobalt ion hyperaccumulation is not suppressed.
• HybridMine: A Pipeline for Allele Inheritance and Gene Copy Number Prediction in Hybrid Genomes and Its Application to Industrial Yeasts
  Timouma, Microorganisms 2020
  • “...Allele Phylogenetic Tree Output SPGP0N03370 YOL158C XP_018222854.1 YOL158C YOL158C SPGP0I00140 YBR296C XP_018223320.1 XP_018223320.1 XP_018223320.1 SPGP0I00180 YBR290W XP_018223316.1 XP_018223316.1 XP_018223316.1 SPGP0J00870 YBR215W XP_018223244.1 YBR215W YBR215W SPGP0J00840 YBR218C XP_018223247.1 YBR218C YBR218C SPGP0R01550 YGL062W XP_018222170.1 YGL062W YGL062W SPGP0I00870 YBR218C XP_018223247.1 XP_018223247.1 XP_018223247.1 SPGP0E03270 YGL062W XP_018222170.1 XP_018222170.1 XP_018222170.1...”
• Widespread Cumulative Influence of Small Effect Size Mutations on Yeast Quantitative Traits
  Hua, Cell systems 2018
  • “...YDL018C, YDR307W, YDR297W, YNL190W, YDR503C, YBR177C, YGR266W, YER019C-A, YLR034C, YOR322C, YGR260W, YDR349C, YJR015W, YPL246C, YMR058W, YBR290W, YLL023C, YDR205W, YHR123W, YJL024C, YJL212C, YLR292C, YPL207W, YKR027W, YIL076W, YBR288C, YJL183W, YKL008C, YJL207C, YML067C, YGR089W, YOR291W, YNL111C, YEL043W, YPL234C, YLR056W, YKL096W-A, YGR157W, YHR060W, YLR039C, YHR079C DATA AND SOFTWARE AVAILABILITY The...”
• Identification of Genes in Saccharomyces cerevisiae that Are Haploinsufficient for Overcoming Amino Acid Starvation
  Bae, G3 (Bethesda, Md.) 2017
  • “...i YDR483W KRE2 1,2-mannosyltransferase of the Golgi; involved in protein mannosylation M , C, v YBR290W BSD2 Heavy metal ion homeostasis protein; facilitates trafficking of Smf1p and Smf2p metal transporters to vacuole where they are degraded; controls metal ion transport, prevents metal hyper-accumulation, functions in copper...”
• Pathways and Mechanisms that Prevent Genome Instability in Saccharomyces cerevisiae
  Putnam, Genetics 2017
  • “...MMS21 YIL066C RNR3 YJL115W ASF1 YBR098W MMS4 YHR200W RPN10 YPL115C BEM3 YIR002C MPH1 YHR031C RRM3 YBR290W BSD2 YCL061C MRC1 YLR357W RSC2 YML102W CAC2 YMR224C MRE11 YHR056C RSC30 YMR038C CCS1 YOL090W MSH2 YOR014W RTS1 YJL194W CDC6 YDR097C MSH6 YJL047C RTT101 YDL017W CDC7 YBR195C MSI1 YER104W RTT105 YFR036W...”
• Conservation of nucleosome positions in duplicated and orthologous gene pairs
  Nishida, TheScientificWorldJournal 2012
  • “...0.966601899 0.955155711 730157 chr02 YBR260C 0.969346019 0.970918059 734634 chr02 YBR279W 0.956081387 0.964626558 761253 + chr02 YBR290W 0.981586823 0.967935658 782587 + chr03 YCL064C 0.957150698 0.95270514 16880 chr03 YCL058W-A 0.969895345 0.992394829 23584 + chr03 YCL057C-A 0.990886192 0.987170576 24325 chr03 YCL057W 0.963062357 0.961804623 24768 + chr03 YCL038C 0.978210537 0.957633548...”
  • “...YDR529C AFUA_4G06790 0.185927497 YDR062W AFUA_6G00300 0.189190157 YOL086C AFUA_7G01010 0.190813468 YOL026C AFUA_5G03630 0.19138562 YIL033C AFUA_3G10000 0.195925157 YBR290W AFUA_4G13740 0.19955841 YAR019C AFUA_4G06750 0.204744755 YHL007C AFUA_2G04680 0.20737573 YMR078C AFUA_7G05480 0.222707833 YDR311W AFUA_4G11690 0.22686955 YOL100W AFUA_3G12670 0.230714484 YGR162W AFUA_2G09490 0.232235851 YGL255W AFUA_1G01550 0.248116851 YPL038W AFUA_6G01910 0.252388553 YCL035C AFUA_1G06100 0.255759517 YNL082W...”
• High-resolution genome-wide scan of genes, gene-networks and cellular systems impacting the yeast ionome
  Yu, BMC genomics 2012
  • “...- - - - - - - - - 3.61 - - - - Mn YBR290W BSD2 B - 9.30 - - - - - 9.15 - - - - - - Mn YGR257C MTM1 C - - - - - - - - 6.97 -...”
• Noise reduction in genome-wide perturbation screens using linear mixed-effect models
  Yu, Bioinformatics (Oxford, England) 2011
  • “...and YPR065W for the KOd screen, and YMR243C, YDL227C, YBR290W and YGL008C for the OE screen), which were grown in four replicates within each plate. The...”
  • “...YPR065W for KO, YLR396C and YPR065W for KOd, and YBR290W and YGL008C for OE) were used to evaluate the quality of the results. Normalization and variance...”
• Exploring the mode of action of antimicrobial peptide MUC7 12-mer by fitness profiling of Saccharomyces cerevisiae genomewide mutant collection
  Lis, Antimicrobial agents and chemotherapy 2009
  • “...YCR087C-A YCR050C YNL025C YDR414C YCR036W YMR154C YHL009C YBR290W YCL001W-A YDR069C YML097C YMR063W YOL004W YDR323C YLR423C YDR443C YBR283C YBR298C YCR024C-A...”
• More
• A novel role for Bsd2 in the resistance of yeast to adriamycin.
  Takahashi, Journal of cellular physiology 2005 (PubMed)
  • GeneRIF: the resistance to adriamycin acquired by overexpression of BSD2 might be partially explained by down-regulation of Smf2
• Bsd2 binds the ubiquitin ligase Rsp5 and mediates the ubiquitination of transmembrane proteins.
  Hettema, The EMBO journal 2004
  • GeneRIF: Bsd2 provides an alternative ubiquitination mechanism for Cps1, Phm5 and other proteins
• Ubiquitin-Activated Interaction Traps (UBAITs) identify E3 ligase binding partners
  O'Connor, EMBO reports 2015
  • “...80 69 0 yes Q12734 ART8 124.8 181 135 155 0 45 55 98 0 yes P38356 BSD2 35.7 5 13 0 0 2 5 0 0 yes P48524 BUL1 109.1 67 89 142 0 47 64 98 0 yes P54005 DIA1 38.7 8...”
• Global gene expression analysis during germination in the chytridiomycete Blastocladiella emersonii
  Salem-Izacc, Eukaryotic cell 2009 (secret)
• Transcriptome analysis in response to heat shock and cadmium in the aquatic fungus Blastocladiella emersonii
  Georg, Eukaryotic cell 2007 (secret)

CNAG_06167 metal homeostatis protein bsd2 from Cryptococcus neoformans var. grubii H99
Aligns to 239:431 / 569 (33.9%), covers 98.5% of PF10176, 128.9 bits

• Golgi Reassembly and Stacking Protein (GRASP) Participates in Vesicle-Mediated RNA Export in Cryptococcus Neoformans
  Peres, Genes 2018
  • “...5 75.4 6.5 231.5 14.71 0.5 141.5 37.66 1 208.5 hypothetical protein Ic12-776 in5UTR 7.38 CNAG_06167 Ic13-990 in5UTR 26.36 5 131.1 11 770 103.14 6.5 152.5 146.05 10.5 295 metal homeostatis protein bsd2 CNAG_01820 Ic3-1947 in3UTR 28.14 12 342.4 47 180.5 236.94 17 15.5 344.85 27.5...”

CNBG_4873 metal homeostatis protein bsd2 from Cryptococcus deuterogattii R265
Aligns to 239:431 / 569 (33.9%), covers 98.5% of PF10176, 128.5 bits

• Highly recombinant VGII Cryptococcus gattii population develops clonal outbreak clusters through both sexual macroevolution and asexual microevolution
  Billmyre, mBio 2014
  • “...100 replicates. The affected region from 393 to 408kb comprises three genes: CNBG_4871, CNBG_4872, and CNBG_4873 ( Fig.9A ). All of these genes showed considerable amino acid polymorphism among C.gattii isolates (see Fig.S2 in the supplemental material). Isolates 2001/935-1 and IP96/1120-1 share amino acid polymorphism with...”
  • “...introgressed region was affected by recombination or the donor is an unknown VG type. In CNBG_4873, the two isolates also have an amino acid at position 44 that was not found in any other C.gattii isolate. The three genes in the affected region from 393 to...”

CH_124344 metal homeostatis protein BSD2 from Magnaporthe grisea 70-15 (see paper)
Aligns to 199:324 / 344 (36.6%), covers 97.7% of PF10176, 101.8 bits

NFIP1_HUMAN / Q9BT67 NEDD4 family-interacting protein 1; Breast cancer-associated protein SGA-1M; NEDD4 WW domain-binding protein 5; Putative MAPK-activating protein PM13; Putative NF-kappa-B-activating protein 164; Putative NFKB and MAPK-activating protein from Homo sapiens (Human) (see 12 papers)
NP_085048 NEDD4 family-interacting protein 1 from Homo sapiens
2 alignments in 110:212 / 221 (46.6%), covering up to 42.3% of PF10176, 97.3 bits

• function: Activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, and consequently modulates the stability of their targets. As a result, controls many cellular processes. Prevents chronic T-helper cell-mediated inflammation by activating ITCH and thus controlling JUNB degradation (By similarity). Promotes pancreatic beta cell death through degradation of JUNB and inhibition of the unfolded protein response, leading to reduction of insulin secretion (PubMed:26319551). Restricts the production of pro- inflammatory cytokines in effector Th17 T-cells by promoting ITCH- mediated ubiquitination and degradation of RORC (By similarity). Together with NDFIP2, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination (By similarity). Regulates peripheral T-cell tolerance to self and foreign antigens, forcing the exit of naive CD4+ T-cells from the cell cycle before they become effector T-cells (By similarity). Negatively regulates RLR-mediated antiviral response by promoting SMURF1-mediated ubiquitination and subsequent degradation of MAVS (PubMed:23087404). Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus where it mediates KCNH2 degradation (PubMed:26363003). In cortical neurons, mediates the ubiquitination of the divalent metal transporter SLC11A2/DMT1 by NEDD4L, leading to its down-regulation and protection of the cells from cobalt and iron toxicity (PubMed:19706893). Important for normal development of dendrites and dendritic spines in cortex (By similarity). Enhances the ubiquitination of BRAT1 mediated by: NEDD4, NEDD4L and ITCH and is required for the nuclear localization of ubiquitinated BRAT1 (PubMed:25631046). Enhances the ITCH-mediated ubiquitination of MAP3K7 by recruiting E2 ubiquitin-conjugating enzyme UBE2L3 to ITCH (By similarity). Modulates EGFR signaling through multiple pathways. In particular, may regulate the ratio of AKT1-to-MAPK8 signaling in response to EGF, acting on AKT1 probably through PTEN destabilization and on MAPK8 through ITCH-dependent MAP2K4 inactivation. As a result, may control cell growth rate (PubMed:20534535). Inhibits cell proliferation by promoting PTEN nuclear localization and changing its signaling specificity (PubMed:25801959).
  subunit: Forms heterodimers with NDFIP2 (PubMed:20534535). Interacts with several E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L and WWP2 (PubMed:18776082, PubMed:19706893, PubMed:26363003). The interaction with NEDD4, NEDD4L and ITCH leads to relocalization of these proteins to exosomes and eventually to exosomal secretion (By similarity). Interacts with U2SURP (By similarity). Interacts with SLC11A2/DMT1 (PubMed:18776082, PubMed:19706893). Interacts with PTEN (PubMed:20534535, PubMed:25801959). May interact with phosphorylated EGFR (PubMed:20534535). Interacts with BRAT1 (PubMed:25631046). Interacts with KCNH2 (PubMed:26363003). Interacts with MAVS (PubMed:23087404). Part of a complex containing ITCH, NDFIP1 and MAP3K7 (By similarity). Interacts (via N-terminus) with UBE2L3; the interaction mediates recruitment of UBE2L3 to ITCH (PubMed:25632008).
• Distinct Molecular Features of NleG Type 3 Secreted Effectors Allow for Different Roles during Citrobacter rodentium Infection in Mice.
  Popov, Infection and immunity 2023
• Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2.
  Barker, PloS one 2020
  • “...2194 Q9UMD9 Collagen alpha-1(XVII) chain extracellular matrix structural protein (PC00103) testis NDFIP1 0.8911 2.91E-125 17592 Q9BT67 NEDD4 family-interacting protein 1 testis SPARC 0.8908 4.67E-125 11219 P09486 SPARC extracellular matrix glycoprotein (PC00100) colon-transverse TINAG 0.8905 2.94E-140 14599 Q9UJW2 Tubulointerstitial nephritis antigen cysteine protease (PC00081) testis SCP2 0.8886...”
• Quantitative Analysis of Ubiquitinated Proteins in Human Pituitary and Pituitary Adenoma Tissues
  Qian, Frontiers in endocrinology 2019
  • “...142 1 8.59E+06 Q96N64 PWWP2A PWWP domain-containing protein 2A TGLEK*MRSGK* 10 496;501 1; 1 1.06E+07 Q9BT67 NDFIP1 NEDD4 family-interacting protein 1 TK*AEATIPLVPGR 13 83 1 Q9BUL8 PDCD10 Programmed cell death protein 10 QILSK*IPDEINDR 13 116 1 2.54E+07 Q9BWQ8 FAIM2 Protein lifeguard 2 APGTEGQQQVHGEK*K 15 25 0.822...”
• Ndfip1 protected dopaminergic neurons via regulating mitochondrial function and ferroptosis in Parkinson's disease.
  Fu, Experimental neurology 2024 (PubMed)
  • GeneRIF: Ndfip1 protected dopaminergic neurons via regulating mitochondrial function and ferroptosis in Parkinson's disease.
• Research progress on the role of Ndfip1 (Nedd4 family interacting protein 1) in immune cells.
  Tang, Allergologia et immunopathologia 2023 (PubMed)
  • GeneRIF: Research progress on the role of Ndfip1 (Nedd4 family interacting protein 1) in immune cells.
• NDFIP1 limits cellular TAZ accumulation via exosomal sorting to inhibit NSCLC proliferation.
  Cheng, Protein & cell 2023
  • GeneRIF: NDFIP1 limits cellular TAZ accumulation via exosomal sorting to inhibit NSCLC proliferation.
• UBA6 and NDFIP1 regulate the degradation of ferroportin.
  Traeger, Haematologica 2022
  • GeneRIF: UBA6 and NDFIP1 regulate the degradation of ferroportin.
• Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients.
  López-Cotarelo, Scientific reports 2021
  • GeneRIF: Genetic variation in NDFIP1 modifies the metabolic patterns in immune cells of multiple sclerosis patients.
• Comparative analysis of the catalytic regulation of NEDD4-1 and WWP2 ubiquitin ligases.
  Jiang, The Journal of biological chemistry 2019
  • GeneRIF: We found that in addition to influencing catalytic activities, the WW domain linker regions in NEDD4-1 and WWP2 can impact product distribution, including the degree of polyubiquitination and Lys-48 versus Lys-63 linkages. We show that allosteric activation by NDFIP1 or engineered ubiquitin variants is largely mediated by relief of WW domain linker autoinhibition.
• MiR-155 Promotes Uveal Melanoma Cell Proliferation and Invasion by Regulating NDFIP1 Expression.
  Peng, Technology in cancer research & treatment 2017
  • GeneRIF: we identified Nedd4-family interacting protein 1 as a direct target of miR-155, and the expression of Nedd4-family interacting protein 1 was inhibited by miR-155. Furthermore, ectopic expression of Nedd4-family interacting protein 1 restored the effects of miR-155 on cell proliferation and invasion of uveal melanoma cells
• Protective effects and mechanisms of Ndfipl on SH-SY5Y cell apoptosis in an in vitro Parkinson's disease model.
  Xing, Genetics and molecular research : GMR 2016 (PubMed)
  • GeneRIF: the expression of Ndfipl reduced expression of a-synuclein. In conclusion, Ndfipl plays a significant role in protecting SH-SY5Y cells in in vitro Parkinson's disease models.
• More

NFIP1_RAT / Q5U2S1 NEDD4 family-interacting protein 1 from Rattus norvegicus (Rat) (see paper)
2 alignments in 110:212 / 221 (46.6%), covering up to 42.3% of PF10176, 97.2 bits

• function: Activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, and consequently modulates the stability of their targets. As a result, controls many cellular processes. Prevents chronic T-helper cell-mediated inflammation by activating ITCH and thus controlling JUNB degradation. Promotes pancreatic beta cell death through degradation of JUNB and inhibition of the unfolded protein response, leading to reduction of insulin secretion. Restricts the production of pro-inflammatory cytokines in effector Th17 T-cells by promoting ITCH-mediated ubiquitination degradation of RORC. Together with NDFIP2, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination. Regulates peripheral T-cell tolerance to self and foreign antigens, forcing the exit of naive CD4+ T-cells from the cell cycle before they become effector T-cells. Negatively regulates RLR- mediated antiviral response by promoting SMURF1-mediated ubiquitination and subsequent degradation of MAVS. Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus where it mediates KCNH2 degradation. In cortical neurons, mediates the ubiquitination of the divalent metal transporter SLC11A2/DMT1 by NEDD4L, leading to its down-regulation and protection of the cells from cobalt and iron toxicity. Important for normal development of dendrites and dendritic spines in cortex. Enhances the ubiquitination of BRAT1 mediated by: NEDD4, NEDD4L and ITCH and is required for the nuclear localization of ubiquitinated BRAT1. Enhances the ITCH-mediated ubiquitination of MAP3K7 by recruiting E2 ubiquitin- conjugating enzyme UBE2L3 to ITCH. Modulates EGFR signaling through multiple pathways. In particular, may regulate the ratio of AKT1-to- MAPK8 signaling in response to EGF, acting on AKT1 probably through PTEN destabilization and on MAPK8 through ITCH-dependent MAP2K4 inactivation. As a result, may control cell growth rate. Inhibits cell proliferation by promoting PTEN nuclear localization and changing its signaling specificity.
  subunit: Forms heterodimers with NDFIP2. Interacts with several E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L and WWP2. The interaction with NEDD4, NEDD4L and ITCH leads to relocalization of these proteins to exosomes and eventually to exosomal secretion. Interacts with SR1402. Interacts with SLC11A2/DMT1. Interacts with PTEN. May interact with phosphorylated EGFR. Interacts with BRAT1. Interacts with KCNH2. Interacts with MAVS. Part of a complex containing ITCH, NDFIP1 and MAP3K7. Interacts (via N-terminus) with UBE2L3; the interaction mediates recruitment of UBE2L3 to ITCH.

NFIP1_MOUSE / Q8R0W6 NEDD4 family-interacting protein 1; NEDD4 WW domain-binding protein 5 from Mus musculus (Mouse) (see 16 papers)
2 alignments in 110:212 / 221 (46.6%), covering up to 42.3% of PF10176, 97.2 bits

• function: Activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, and consequently modulates the stability of their targets. As a result, controls many cellular processes. Prevents chronic T-helper cell-mediated inflammation by activating ITCH and thus controlling JUNB degradation (PubMed:11748237, PubMed:17137798, PubMed:20962770). Promotes pancreatic beta cell death through degradation of JUNB and inhibition of the unfolded protein response, leading to reduction of insulin secretion (PubMed:26319551). Restricts the production of pro-inflammatory cytokines in effector Th17 T-cells by promoting ITCH-mediated ubiquitination and degradation of RORC (PubMed:28051111). Together with NDFIP2, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination (PubMed:27088444). Regulates peripheral T-cell tolerance to self and foreign antigens, forcing the exit of naive CD4+ T-cells from the cell cycle before they become effector T-cells (PubMed:24520172, PubMed:28051111). Negatively regulates RLR-mediated antiviral response by promoting SMURF1-mediated ubiquitination and subsequent degradation of MAVS (By similarity). Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus where it mediates KCNH2 degradation (By similarity). In cortical neurons, mediates the ubiquitination of the divalent metal transporter SLC11A2/DMT1 by NEDD4L, leading to its down-regulation and protection of the cells from cobalt and iron toxicity (By similarity). Important for normal development of dendrites and dendritic spines in cortex (PubMed:23897647). Enhances the ubiquitination of BRAT1 mediated by: NEDD4, NEDD4L and ITCH and is required for the nuclear localization of ubiquitinated BRAT1 (PubMed:25631046). Enhances the ITCH-mediated ubiquitination of MAP3K7 by recruiting E2 ubiquitin-conjugating enzyme UBE2L3 to ITCH (PubMed:25632008). Modulates EGFR signaling through multiple pathways. In particular, may regulate the ratio of AKT1-to-MAPK8 signaling in response to EGF, acting on AKT1 probably through PTEN destabilization and on MAPK8 through ITCH-dependent MAP2K4 inactivation. As a result, may control cell growth rate (By similarity). Inhibits cell proliferation by promoting PTEN nuclear localization and changing its signaling specificity (PubMed:25801959).
  subunit: Forms heterodimers with NDFIP2 (By similarity). Interacts with several E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L and WWP2 (PubMed:11042109, PubMed:11748237, PubMed:17137798, PubMed:25632008). The interaction with NEDD4, NEDD4L and ITCH leads to relocalization of these proteins to exosomes and eventually to exosomal secretion (PubMed:11748237). Interacts with U2SURP (PubMed:11748237). Interacts with SLC11A2/DMT1 (By similarity). Interacts with PTEN (By similarity). May interact with phosphorylated EGFR (By similarity). Interacts with BRAT1 (By similarity). Interacts with KCNH2 (By similarity). Interacts with MAVS (By similarity). Part of a complex containing ITCH, NDFIP1 and MAP3K7 (PubMed:25632008). Interacts (via N- terminus) with UBE2L3; the interaction mediates recruitment of UBE2L3 to ITCH (PubMed:25632008).
  disruption phenotype: Mutant mice appear normal at birth, but develop severe skin and gastrointestinal tract inflammation around 6 to 8 weeks of age (PubMed:17137798, PubMed:20962770). They do not survive beyond 14 weeks (PubMed:17137798). This phenotype is due to the lack of activity of ITCH E3 ubiquitin-protein ligase, and consequently, prolongation of JUNB half-life after T-cell activation (PubMed:17137798, PubMed:20962770). This results in an increased production of T-helper 2 (Th2) cytokines and in the promotion of Th2- mediated inflammation (PubMed:17137798, PubMed:20962770). This subsequently leads to increased number of circulating, esophagus and small bowel eosinophils (PubMed:20962770). Mutant mice have thicker small bowel and do not gain as much weight as the wild type (PubMed:20962770). Mutant mice also show an increased iron transport in hepatocytes and iron accumulation in the liver around portal veins, in the villi of duodenum and throughout the brain cortex (PubMed:18776082, PubMed:19706893).

Q3V1V0 Nedd4 family interacting protein 2 from Mus musculus
2 alignments in 130:232 / 241 (42.7%), covering up to 43.8% of PF10176, 95.7 bits

• Substrate clustering potently regulates the activity of WW-HECT domain-containing ubiquitin ligases.
  Mund, The Journal of biological chemistry 2018
  • “...and the cytoplasmic domain of mouse NDFIP2 containing the three PY motifs (aa 1117, UniProtKB Q3V1V0). For live-cell imaging studies, Nedd4 and the trypsin-resistant tandem ubiquitin binding entity TR-TUBE ( 43 ) were N-terminally tagged with mCherry. The following PY motifcontaining C-terminal arrestin fragments were cloned...”

NFIP2_MOUSE / Q91ZP6 NEDD4 family-interacting protein 2; NEDD4 WW domain-binding protein 5A from Mus musculus (Mouse) (see 3 papers)
2 alignments in 200:302 / 311 (33.1%), covering up to 43.8% of PF10176, 94.5 bits

• function: Activates HECT domain-containing E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L, SMURF2, WWP1 and WWP2, and consequently modulates the stability of their targets. As a result, may control many cellular processes. Recruits ITCH, NEDD4 and SMURF2 to endosomal membranes. Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus and multivesicular body where it mediates KCNH2 degradation (By similarity). May modulate EGFR signaling (By similarity). Together with NDFIP1, limits the cytokine signaling and expansion of effector Th2 T- cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L- mediated ubiquitination (PubMed:27088444).
  subunit: Forms heterodimers with NDFIP1 (By similarity). Interacts with HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 (PubMed:12050153, PubMed:15252135). Interacts with NEDD4L (PubMed:12050153). When phosphorylated at Tyr-142, interacts with SRC and LYN SH2 domain (By similarity). May thus act as a scaffold that recruits SRC to NDFIP1, enhancing NDFIP1 phosphorylation (By similarity). Interacts with SLC11A2/DMT1 (By similarity). May interact with phosphorylated EGFR (By similarity). Interacts with KCNH2 (By similarity).
  disruption phenotype: Mutant mice show no signs of inflammation and have normal T-cell populations in thymus, lymph nodes and spleen.

NP_083837 NEDD4 family-interacting protein 2 from Mus musculus
2 alignments in 227:329 / 338 (30.5%), covering up to 43.8% of PF10176, 94.1 bits

• Ndfip2 is a potential regulator of the iron transporter DMT1 in the liver.
  Foot, Scientific reports 2016
  • GeneRIF: Ndfip2 controls DMT1 in the liver with female mice showing a greater response to altered dietary iron than the male mice
• Ndfip-mediated degradation of Jak1 tunes cytokine signalling to limit expansion of CD4+ effector T cells.
  O'Leary, Nature communications 2016
  • GeneRIF: Data indicate thar Janus kinase 1 (Jak1) degradation is dependent on Nedd4 family interacting proteins Ndfip1/Ndfip2.
• Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2.
  Foot, Blood 2008 (PubMed)
  • GeneRIF: DMT1 interacts with 2 WW domain-interacting proteins, Ndfip1 and Ndfip2. This promotes DMT1 ubiquitination and degradation by WWP2.

NFIP2_HUMAN / Q9NV92 NEDD4 family-interacting protein 2; NEDD4 WW domain-binding protein 5A; Putative MAPK-activating protein PM04/PM05/PM06/PM07; Putative NF-kappa-B-activating protein 413 from Homo sapiens (Human) (see 6 papers)
2 alignments in 225:327 / 336 (30.7%), covering up to 43.8% of PF10176, 94.1 bits

• function: Activates HECT domain-containing E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L, SMURF2, WWP1 and WWP2, and consequently modulates the stability of their targets. As a result, may control many cellular processes. Recruits ITCH, NEDD4 and SMURF2 to endosomal membranes. Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus and multivesicular body where it mediates KCNH2 degradation (PubMed:26363003). May modulate EGFR signaling. Together with NDFIP1, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination (By similarity).
  subunit: Forms heterodimers with NDFIP1. Interacts with HECT domain- containing E3 ubiquitin-protein ligases, including NEDD4 (PubMed:12796489). Interacts with NEDD4L (PubMed:26363003). Interacts with PTEN. When phosphorylated at Tyr-167, interacts with SRC and LYN SH2 domain. May thus act as a scaffold that recruits SRC to NDFIP1, enhancing NDFIP1 phosphorylation. Interacts with SLC11A2/DMT1 (PubMed:18776082). May interact with phosphorylated EGFR. Interacts with KCNH2 (PubMed:26363003).
• Uncharacterized Proteins CxORFx: Subinteractome Analysis and Prognostic Significance in Cancers
  Ershov, International journal of molecular sciences 2023
  • “...FBXW8 (Q8N3Y1), GAPDHS (O14556), GPR161 (Q8N6U8), JUN (P05412), KPNA1 (P52294), MDM2 (Q00987), MEIS2 (O14770), NDFIP2 (Q9NV92), NUP214 (P35658), OPTN (Q96CV9), PBX1 (P40424), PPP2R1A (P30153), PRKACA (P17612), PRKAR1A (P10644), PTPRJ (Q12913), RNF123 (Q5XPI4), SMARCAD1 (Q9H4L7), SPAG5 (Q96R06) and WWP2 (O00308). ijms-24-10190-t004_Table 4 Table 4 Relevant literature data...”

F1ML71 Nedd4 family interacting protein 2 from Bos taurus
2 alignments in 258:360 / 369 (27.9%), covering up to 43.8% of PF10176, 94.0 bits

• Proteomics analysis reveals heat shock proteins involved in caprine parainfluenza virus type 3 infection
  Zhong, BMC veterinary research 2019
  • “...1.26 0.793650794 down F1N5R4 Conserved oligomeric Golgi complex subunit 8 (COG8) 1 1.271 0.786782061 down F1ML71 Nedd4 family interacting protein 2 (NDFIP2) 1 1.254 0.797448166 down G3N266 G protein signaling modulator 1 (GPSM1) 1 1.235 0.809716599 down F1N0K0 Collagen alpha-1(XI) chain (COL11A1) 1 1.212 0.825082508 down...”

Or search for genetic data about PF10176 in the Fitness Browser