NFIP1_MOUSE
ID NFIP1_MOUSE Reviewed; 221 AA.
AC Q8R0W6; Q9EQH8;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=NEDD4 family-interacting protein 1;
DE AltName: Full=NEDD4 WW domain-binding protein 5;
GN Name=Ndfip1; Synonyms=N4wbp5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF TYR-42 AND TYR-67, INTERACTION
RP WITH NEDD4, AND DOMAINS.
RC TISSUE=Embryo;
RX PubMed=11042109; DOI=10.1042/bj3510557;
RA Jolliffe C.N., Harvey K.F., Haines B.P., Parasivam G., Kumar S.;
RT "Identification of multiple proteins expressed in murine embryos as binding
RT partners for the WW domains of the ubiquitin-protein ligase Nedd4.";
RL Biochem. J. 351:557-565(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH NEDD4; NEDD4L; U2SURP; WWP2
RP AND ITCH, DOMAIN, UBIQUITINATION BY NEDD4, AND SUBCELLULAR LOCATION.
RX PubMed=11748237; DOI=10.1074/jbc.m110443200;
RA Harvey K.F., Shearwin-Whyatt L.M., Fotia A., Parton R.G., Kumar S.;
RT "N4WBP5, a potential target for ubiquitination by the Nedd4 family of
RT proteins, is a novel Golgi-associated protein.";
RL J. Biol. Chem. 277:9307-9317(2002).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH ITCH, AND TISSUE
RP SPECIFICITY.
RX PubMed=17137798; DOI=10.1016/j.immuni.2006.10.012;
RA Oliver P.M., Cao X., Worthen G.S., Shi P., Briones N., MacLeod M.,
RA White J., Kirby P., Kappler J., Marrack P., Yang B.;
RT "Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T
RT cell activation and T helper 2 cell-mediated inflammation.";
RL Immunity 25:929-940(2006).
RN [6]
RP SUBCELLULAR LOCATION, AND INDUCTION BY TRAUMATIC BRAIN INJURY.
RX PubMed=16822981; DOI=10.1523/jneurosci.1398-06.2006;
RA Sang Q., Kim M.H., Kumar S., Bye N., Morganti-Kossman M.C., Gunnersen J.,
RA Fuller S., Howitt J., Hyde L., Beissbarth T., Scott H.S., Silke J.,
RA Tan S.S.;
RT "Nedd4-WW domain-binding protein 5 (Ndfip1) is associated with neuronal
RT survival after acute cortical brain injury.";
RL J. Neurosci. 26:7234-7244(2006).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=18776082; DOI=10.1182/blood-2008-04-150953;
RA Foot N.J., Dalton H.E., Shearwin-Whyatt L.M., Dorstyn L., Tan S.S.,
RA Yang B., Kumar S.;
RT "Regulation of the divalent metal ion transporter DMT1 and iron homeostasis
RT by a ubiquitin-dependent mechanism involving Ndfips and WWP2.";
RL Blood 112:4268-4275(2008).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=18819914; DOI=10.1074/jbc.m804120200;
RA Putz U., Howitt J., Lackovic J., Foot N., Kumar S., Silke J., Tan S.S.;
RT "Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal
RT secretion of Nedd4 family proteins.";
RL J. Biol. Chem. 283:32621-32627(2008).
RN [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=19706893; DOI=10.1073/pnas.0904880106;
RA Howitt J., Putz U., Lackovic J., Doan A., Dorstyn L., Cheng H., Yang B.,
RA Chan-Ling T., Silke J., Kumar S., Tan S.S.;
RT "Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal
RT toxicity in human neurons.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:15489-15494(2009).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20962770; DOI=10.1038/mi.2010.69;
RA Ramon H.E., Riling C.R., Bradfield J., Yang B., Hakonarson H., Oliver P.M.;
RT "The ubiquitin ligase adaptor Ndfip1 regulates T cell-mediated
RT gastrointestinal inflammation and inflammatory bowel disease
RT susceptibility.";
RL Mucosal Immunol. 4:314-324(2011).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23897647; DOI=10.1093/cercor/bht191;
RA Hammond V.E., Gunnersen J.M., Goh C.P., Low L.H., Hyakumura T., Tang M.M.,
RA Britto J.M., Putz U., Howitt J.A., Tan S.S.;
RT "Ndfip1 is required for the development of pyramidal neuron dendrites and
RT spines in the neocortex.";
RL Cereb. Cortex 24:3289-3300(2014).
RN [12]
RP FUNCTION.
RX PubMed=24520172; DOI=10.1073/pnas.1322739111;
RA Altin J.A., Daley S.R., Howitt J., Rickards H.J., Batkin A.K., Horikawa K.,
RA Prasad S.J., Nelms K.A., Kumar S., Wu L.C., Tan S.S., Cook M.C.,
RA Goodnow C.C.;
RT "Ndfip1 mediates peripheral tolerance to self and exogenous antigen by
RT inducing cell cycle exit in responding CD4+ T cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:2067-2074(2014).
RN [13]
RP FUNCTION.
RX PubMed=26319551; DOI=10.1016/j.bbrc.2015.08.099;
RA Beck A., Shatz-Azoulay H., Vinik Y., Isaac R., Boura-Halfon S., Zick Y.;
RT "Nedd4 family interacting protein 1 (Ndfip1) promotes death of pancreatic
RT beta cells.";
RL Biochem. Biophys. Res. Commun. 465:851-856(2015).
RN [14]
RP FUNCTION.
RX PubMed=25631046; DOI=10.1074/jbc.m114.613687;
RA Low L.H., Chow Y.L., Li Y., Goh C.P., Putz U., Silke J., Ouchi T.,
RA Howitt J., Tan S.S.;
RT "Nedd4 family interacting protein 1 (Ndfip1) is required for ubiquitination
RT and nuclear trafficking of BRCA1-associated ATM activator 1 (BRAT1) during
RT the DNA damage response.";
RL J. Biol. Chem. 290:7141-7150(2015).
RN [15]
RP FUNCTION, INTERACTION WITH UBE2L3 AND ITCH, AND IDENTIFICATION IN COMPLEX
RP WITH ITCH AND MAP3K7.
RX PubMed=25632008; DOI=10.4049/jimmunol.1402742;
RA Kathania M., Zeng M., Yadav V.N., Moghaddam S.J., Yang B., Venuprasad K.;
RT "Ndfip1 regulates itch ligase activity and airway inflammation via UbcH7.";
RL J. Immunol. 194:2160-2167(2015).
RN [16]
RP FUNCTION.
RX PubMed=25801959; DOI=10.1093/jmcb/mjv020;
RA Howitt J., Low L.H., Putz U., Doan A., Lackovic J., Goh C.P., Gunnersen J.,
RA Silke J., Tan S.S.;
RT "Ndfip1 represses cell proliferation by controlling Pten localization and
RT signaling specificity.";
RL J. Mol. Cell Biol. 7:119-131(2015).
RN [17]
RP FUNCTION.
RX PubMed=27088444; DOI=10.1038/ncomms11226;
RA O'Leary C.E., Riling C.R., Spruce L.A., Ding H., Kumar S., Deng G., Liu Y.,
RA Seeholzer S.H., Oliver P.M.;
RT "Ndfip-mediated degradation of Jak1 tunes cytokine signalling to limit
RT expansion of CD4+ effector T cells.";
RL Nat. Commun. 7:11226-11226(2016).
RN [18]
RP FUNCTION.
RX PubMed=28051111; DOI=10.1038/srep39649;
RA Kesewa Layman A.A., Sprout S.L., Phillips D., Oliver P.M.;
RT "Ndfip1 restricts Th17 cell potency by limiting lineage stability and
RT proinflammatory cytokine production.";
RL Sci. Rep. 7:39649-39649(2017).
CC -!- FUNCTION: Activates HECT domain-containing E3 ubiquitin-protein
CC ligases, including NEDD4 and ITCH, and consequently modulates the
CC stability of their targets. As a result, controls many cellular
CC processes. Prevents chronic T-helper cell-mediated inflammation by
CC activating ITCH and thus controlling JUNB degradation (PubMed:11748237,
CC PubMed:17137798, PubMed:20962770). Promotes pancreatic beta cell death
CC through degradation of JUNB and inhibition of the unfolded protein
CC response, leading to reduction of insulin secretion (PubMed:26319551).
CC Restricts the production of pro-inflammatory cytokines in effector Th17
CC T-cells by promoting ITCH-mediated ubiquitination and degradation of
CC RORC (PubMed:28051111). Together with NDFIP2, limits the cytokine
CC signaling and expansion of effector Th2 T-cells by promoting
CC degradation of JAK1, probably by ITCH- and NEDD4L-mediated
CC ubiquitination (PubMed:27088444). Regulates peripheral T-cell tolerance
CC to self and foreign antigens, forcing the exit of naive CD4+ T-cells
CC from the cell cycle before they become effector T-cells
CC (PubMed:24520172, PubMed:28051111). Negatively regulates RLR-mediated
CC antiviral response by promoting SMURF1-mediated ubiquitination and
CC subsequent degradation of MAVS (By similarity). Negatively regulates
CC KCNH2 potassium channel activity by decreasing its cell-surface
CC expression and interfering with channel maturation through recruitment
CC of NEDD4L to the Golgi apparatus where it mediates KCNH2 degradation
CC (By similarity). In cortical neurons, mediates the ubiquitination of
CC the divalent metal transporter SLC11A2/DMT1 by NEDD4L, leading to its
CC down-regulation and protection of the cells from cobalt and iron
CC toxicity (By similarity). Important for normal development of dendrites
CC and dendritic spines in cortex (PubMed:23897647). Enhances the
CC ubiquitination of BRAT1 mediated by: NEDD4, NEDD4L and ITCH and is
CC required for the nuclear localization of ubiquitinated BRAT1
CC (PubMed:25631046). Enhances the ITCH-mediated ubiquitination of MAP3K7
CC by recruiting E2 ubiquitin-conjugating enzyme UBE2L3 to ITCH
CC (PubMed:25632008). Modulates EGFR signaling through multiple pathways.
CC In particular, may regulate the ratio of AKT1-to-MAPK8 signaling in
CC response to EGF, acting on AKT1 probably through PTEN destabilization
CC and on MAPK8 through ITCH-dependent MAP2K4 inactivation. As a result,
CC may control cell growth rate (By similarity). Inhibits cell
CC proliferation by promoting PTEN nuclear localization and changing its
CC signaling specificity (PubMed:25801959). {ECO:0000250|UniProtKB:Q9BT67,
CC ECO:0000269|PubMed:11748237, ECO:0000269|PubMed:17137798,
CC ECO:0000269|PubMed:20962770, ECO:0000269|PubMed:23897647,
CC ECO:0000269|PubMed:24520172, ECO:0000269|PubMed:25631046,
CC ECO:0000269|PubMed:25632008, ECO:0000269|PubMed:25801959,
CC ECO:0000269|PubMed:26319551, ECO:0000269|PubMed:27088444,
CC ECO:0000269|PubMed:28051111}.
CC -!- SUBUNIT: Forms heterodimers with NDFIP2 (By similarity). Interacts with
CC several E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L and
CC WWP2 (PubMed:11042109, PubMed:11748237, PubMed:17137798,
CC PubMed:25632008). The interaction with NEDD4, NEDD4L and ITCH leads to
CC relocalization of these proteins to exosomes and eventually to exosomal
CC secretion (PubMed:11748237). Interacts with U2SURP (PubMed:11748237).
CC Interacts with SLC11A2/DMT1 (By similarity). Interacts with PTEN (By
CC similarity). May interact with phosphorylated EGFR (By similarity).
CC Interacts with BRAT1 (By similarity). Interacts with KCNH2 (By
CC similarity). Interacts with MAVS (By similarity). Part of a complex
CC containing ITCH, NDFIP1 and MAP3K7 (PubMed:25632008). Interacts (via N-
CC terminus) with UBE2L3; the interaction mediates recruitment of UBE2L3
CC to ITCH (PubMed:25632008). {ECO:0000250|UniProtKB:Q9BT67,
CC ECO:0000269|PubMed:11042109, ECO:0000269|PubMed:11748237,
CC ECO:0000269|PubMed:17137798, ECO:0000269|PubMed:25632008}.
CC -!- INTERACTION:
CC Q8R0W6; P46935: Nedd4; NbExp=5; IntAct=EBI-6304119, EBI-773516;
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:Q9BT67};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9BT67}. Golgi
CC apparatus membrane {ECO:0000269|PubMed:11748237,
CC ECO:0000269|PubMed:16822981, ECO:0000269|PubMed:18819914}. Synapse,
CC synaptosome {ECO:0000269|PubMed:23897647}. Cell projection, dendrite
CC {ECO:0000269|PubMed:23897647}. Secreted {ECO:0000250|UniProtKB:Q9BT67}.
CC Note=Detected in exosomes and secreted via the exosomal pathway.
CC {ECO:0000250|UniProtKB:Q9BT67}.
CC -!- TISSUE SPECIFICITY: Highly expressed in embryonic and early postnatal
CC cortex (at protein level) (PubMed:23897647). Widely expressed
CC (PubMed:11748237). Hardly detectable in resting T-cells; up-regulated
CC in T-cells in response to activation (PubMed:17137798).
CC {ECO:0000269|PubMed:11748237, ECO:0000269|PubMed:17137798,
CC ECO:0000269|PubMed:23897647}.
CC -!- INDUCTION: Up-regulated after traumatic brain injury in surviving
CC neurons around the lesion site. {ECO:0000269|PubMed:16822981}.
CC -!- DOMAIN: The PPxY motifs are required for E3 ubiquitin-protein ligase
CC binding and activation and for ubiquitination.
CC {ECO:0000269|PubMed:11042109, ECO:0000269|PubMed:11748237}.
CC -!- PTM: Ubiquitinated by NEDD4; mono-, di- and polyubiquitinated forms are
CC detected. Ubiquitination regulates its degradation.
CC {ECO:0000269|PubMed:11748237}.
CC -!- PTM: Undergoes transient tyrosine phosphorylation following EGF
CC stimulation, most probably by catalyzed by SRC. Phosphorylation SRC is
CC enhanced in the presence of NDFIP2 which may act as a scaffold to
CC recruit SRC to NDFIP1 (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice appear normal at birth, but develop
CC severe skin and gastrointestinal tract inflammation around 6 to 8 weeks
CC of age (PubMed:17137798, PubMed:20962770). They do not survive beyond
CC 14 weeks (PubMed:17137798). This phenotype is due to the lack of
CC activity of ITCH E3 ubiquitin-protein ligase, and consequently,
CC prolongation of JUNB half-life after T-cell activation
CC (PubMed:17137798, PubMed:20962770). This results in an increased
CC production of T-helper 2 (Th2) cytokines and in the promotion of Th2-
CC mediated inflammation (PubMed:17137798, PubMed:20962770). This
CC subsequently leads to increased number of circulating, esophagus and
CC small bowel eosinophils (PubMed:20962770). Mutant mice have thicker
CC small bowel and do not gain as much weight as the wild type
CC (PubMed:20962770). Mutant mice also show an increased iron transport in
CC hepatocytes and iron accumulation in the liver around portal veins, in
CC the villi of duodenum and throughout the brain cortex (PubMed:18776082,
CC PubMed:19706893). {ECO:0000269|PubMed:17137798,
CC ECO:0000269|PubMed:18776082, ECO:0000269|PubMed:19706893,
CC ECO:0000269|PubMed:20962770}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG44248.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF220209; AAG44248.1; ALT_INIT; mRNA.
DR EMBL; AK050560; BAC34324.1; -; mRNA.
DR EMBL; BC026372; AAH26372.1; -; mRNA.
DR CCDS; CCDS37789.1; -.
DR RefSeq; NP_075372.1; NM_022996.1.
DR RefSeq; XP_006526212.1; XM_006526149.1.
DR AlphaFoldDB; Q8R0W6; -.
DR BioGRID; 211136; 12.
DR IntAct; Q8R0W6; 1.
DR STRING; 10090.ENSMUSP00000025293; -.
DR iPTMnet; Q8R0W6; -.
DR PhosphoSitePlus; Q8R0W6; -.
DR SwissPalm; Q8R0W6; -.
DR EPD; Q8R0W6; -.
DR MaxQB; Q8R0W6; -.
DR PaxDb; Q8R0W6; -.
DR PeptideAtlas; Q8R0W6; -.
DR PRIDE; Q8R0W6; -.
DR ProteomicsDB; 287407; -.
DR Antibodypedia; 2434; 211 antibodies from 32 providers.
DR Ensembl; ENSMUST00000025293; ENSMUSP00000025293; ENSMUSG00000024425.
DR Ensembl; ENSMUST00000236085; ENSMUSP00000158314; ENSMUSG00000024425.
DR GeneID; 65113; -.
DR KEGG; mmu:65113; -.
DR UCSC; uc008esj.1; mouse.
DR CTD; 80762; -.
DR MGI; MGI:1929601; Ndfip1.
DR VEuPathDB; HostDB:ENSMUSG00000024425; -.
DR eggNOG; KOG4812; Eukaryota.
DR GeneTree; ENSGT00390000012721; -.
DR HOGENOM; CLU_074980_2_0_1; -.
DR InParanoid; Q8R0W6; -.
DR OMA; TGRQPHH; -.
DR OrthoDB; 1495850at2759; -.
DR PhylomeDB; Q8R0W6; -.
DR TreeFam; TF324911; -.
DR BioGRID-ORCS; 65113; 0 hits in 110 CRISPR screens.
DR ChiTaRS; Ndfip1; mouse.
DR PRO; PR:Q8R0W6; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q8R0W6; protein.
DR Bgee; ENSMUSG00000024425; Expressed in subparaventricular zone and 271 other tissues.
DR ExpressionAtlas; Q8R0W6; baseline and differential.
DR Genevisible; Q8R0W6; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005938; C:cell cortex; IDA:MGI.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0030173; C:integral component of Golgi membrane; IC:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISM:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0050699; F:WW domain binding; IPI:MGI.
DR GO; GO:0035739; P:CD4-positive, alpha-beta T cell proliferation; IMP:MGI.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISO:MGI.
DR GO; GO:0030001; P:metal ion transport; IBA:GO_Central.
DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:MGI.
DR GO; GO:0032713; P:negative regulation of interleukin-4 production; IMP:MGI.
DR GO; GO:0048294; P:negative regulation of isotype switching to IgE isotypes; IMP:MGI.
DR GO; GO:0051224; P:negative regulation of protein transport; ISO:MGI.
DR GO; GO:0032410; P:negative regulation of transporter activity; ISO:MGI.
DR GO; GO:0002829; P:negative regulation of type 2 immune response; IMP:MGI.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; IDA:MGI.
DR GO; GO:0048302; P:regulation of isotype switching to IgG isotypes; IMP:MGI.
DR GO; GO:0045619; P:regulation of lymphocyte differentiation; IMP:MGI.
DR GO; GO:0002761; P:regulation of myeloid leukocyte differentiation; IMP:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0007034; P:vacuolar transport; IEA:InterPro.
DR InterPro; IPR019325; NEDD4/Bsd2.
DR PANTHER; PTHR13396; PTHR13396; 1.
DR Pfam; PF10176; DUF2370; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell projection; Endosome; Golgi apparatus; Membrane;
KW Reference proteome; Repeat; Secreted; Synapse; Synaptosome; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9BT67"
FT CHAIN 2..221
FT /note="NEDD4 family-interacting protein 1"
FT /id="PRO_0000076270"
FT TOPO_DOM 2..116
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..143
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..172
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..221
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 2..41
FT /note="Interaction with UBE2L3"
FT /evidence="ECO:0000269|PubMed:25632008"
FT REGION 18..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 42..76
FT /note="Interaction with ITCH"
FT /evidence="ECO:0000269|PubMed:25632008"
FT MOTIF 39..42
FT /note="PPxY motif 1"
FT MOTIF 64..67
FT /note="PPxY motif 2"
FT MOTIF 74..76
FT /note="PPxY motif 3"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9BT67"
FT MUTAGEN 42
FT /note="Y->A: Abolishes interaction with NEDD4."
FT /evidence="ECO:0000269|PubMed:11042109"
FT MUTAGEN 67
FT /note="Y->A: Alters interaction with NEDD4."
FT /evidence="ECO:0000269|PubMed:11042109"
SQ SEQUENCE 221 AA; 24914 MW; 7699A062161AC6A4 CRC64;
MALALAALAA VEPACGSGYQ QLQNEEEPGE PEQTAGDAPP PYSSITAESA AYFDYKDESG
FPKPPSYNVA TTLPSYDEAE RTKTEATIPL VPGRDEDFVG RDDFDDTDQL RIGNDGIFML
TFFMAFLFNW IGFFLSFCLT TSAAGRYGAI SGFGLSLIKW ILIVRFSTYF PGYFDGQYWL
WWVFLVLGFL LFLRGFINYA KVRKMPETFS NLPRTRVLFI Y
