ID NFIP1_HUMAN Reviewed; 221 AA. AC Q9BT67; B2RDB8; D3DQF0; Q658T8; Q8N2E3; Q8N2F9; DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 27-MAR-2024, entry version 155. DE RecName: Full=NEDD4 family-interacting protein 1; DE AltName: Full=Breast cancer-associated protein SGA-1M; DE AltName: Full=NEDD4 WW domain-binding protein 5; DE AltName: Full=Putative MAPK-activating protein PM13; DE AltName: Full=Putative NF-kappa-B-activating protein 164; DE AltName: Full=Putative NFKB and MAPK-activating protein; GN Name=NDFIP1; Synonyms=N4WBP5; ORFNames=PSEC0192, PSEC0223; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Petroziello J.M., Westendorf L.E., Gordon K.A., Yamane A.K., Cerveny C.G., RA Wahl A.F., Law C.L.; RT "Array analysis of subtractive cDNA libraries identifies SGA-1M: a novel RT breast cancer-associated gene."; RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung fibroblast; RX PubMed=12761501; DOI=10.1038/sj.onc.1206406; RA Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y., RA Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S.; RT "Large-scale identification and characterization of human genes that RT activate NF-kappaB and MAPK signaling pathways."; RL Oncogene 22:3307-3318(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Embryo; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Embryo; RX PubMed=16303743; DOI=10.1093/dnares/12.2.117; RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y., RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., RA Isogai T.; RT "Signal sequence and keyword trap in silico for selection of full-length RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA RT libraries."; RL DNA Res. 12:117-126(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 102-221 (ISOFORM 1). RC TISSUE=Stomach; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP TISSUE SPECIFICITY. 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 [9] RP SUBCELLULAR LOCATION, AND INTERACTION WITH SLC11A2 AND WWP2. 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 [10] 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 [11] RP FUNCTION, AND UBIQUITINATION. RX PubMed=19343052; DOI=10.1038/embor.2009.30; RA Mund T., Pelham H.R.; RT "Control of the activity of WW-HECT domain E3 ubiquitin ligases by NDFIP RT proteins."; RL EMBO Rep. 10:501-507(2009). RN [12] RP FUNCTION, INTERACTION WITH SLC11A2 AND NEDD4L, AND INDUCTION BY COBALT AND RP IRON. 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 [13] RP FUNCTION, INTERACTION WITH NDFIP2; NEDD4 AND PTEN, SUBCELLULAR LOCATION, RP PHOSPHORYLATION, AND MUTAGENESIS OF 41-PRO-TYR-42; 66-SER-TYR-67 AND RP 75-SER-TYR-76. RX PubMed=20534535; DOI=10.1073/pnas.0911714107; RA Mund T., Pelham H.R.; RT "Regulation of PTEN/Akt and MAP kinase signaling pathways by the ubiquitin RT ligase activators Ndfip1 and Ndfip2."; RL Proc. Natl. Acad. Sci. U.S.A. 107:11429-11434(2010). RN [14] RP FUNCTION, AND INTERACTION WITH MAVS. RX PubMed=23087404; DOI=10.4049/jimmunol.1201445; RA Wang Y., Tong X., Ye X.; RT "Ndfip1 negatively regulates RIG-I-dependent immune signaling by enhancing RT E3 ligase Smurf1-mediated MAVS degradation."; RL J. Immunol. 189:5304-5313(2012). RN [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [16] 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 [17] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH KCNH2 AND NEDD4L. RX PubMed=26363003; DOI=10.1042/bj20141282; RA Kang Y., Guo J., Yang T., Li W., Zhang S.; RT "Regulation of the human ether-a-go-go-related gene (hERG) potassium RT channel by Nedd4 family interacting proteins (Ndfips)."; RL Biochem. J. 472:71-82(2015). RN [18] RP FUNCTION, AND INTERACTION WITH BRAT1. 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 [19] RP INTERACTION WITH UBE2L3. 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 [20] RP FUNCTION, AND INTERACTION WITH PTEN. 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). 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 (By similarity). CC Promotes pancreatic beta cell death through degradation of JUNB and CC inhibition of the unfolded protein response, leading to reduction of CC insulin secretion (PubMed:26319551). Restricts the production of pro- CC inflammatory cytokines in effector Th17 T-cells by promoting ITCH- CC mediated ubiquitination and degradation of RORC (By similarity). CC Together with NDFIP2, limits the cytokine signaling and expansion of CC effector Th2 T-cells by promoting degradation of JAK1, probably by CC ITCH- and NEDD4L-mediated ubiquitination (By similarity). Regulates CC peripheral T-cell tolerance to self and foreign antigens, forcing the CC exit of naive CD4+ T-cells from the cell cycle before they become CC effector T-cells (By similarity). Negatively regulates RLR-mediated CC antiviral response by promoting SMURF1-mediated ubiquitination and CC subsequent degradation of MAVS (PubMed:23087404). 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 (PubMed:26363003). 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 (PubMed:19706893). Important for normal development of CC dendrites and dendritic spines in cortex (By similarity). 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 (By CC similarity). Modulates EGFR signaling through multiple pathways. In CC 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 (PubMed:20534535). Inhibits cell CC proliferation by promoting PTEN nuclear localization and changing its CC signaling specificity (PubMed:25801959). {ECO:0000250|UniProtKB:Q8R0W6, CC ECO:0000269|PubMed:19343052, ECO:0000269|PubMed:19706893, CC ECO:0000269|PubMed:20534535, ECO:0000269|PubMed:23087404, CC ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:25801959, CC ECO:0000269|PubMed:26319551, ECO:0000269|PubMed:26363003}. CC -!- SUBUNIT: Forms heterodimers with NDFIP2 (PubMed:20534535). Interacts CC with several E3 ubiquitin-protein ligases, including ITCH, NEDD4, CC NEDD4L and WWP2 (PubMed:18776082, PubMed:19706893, PubMed:26363003). CC The interaction with NEDD4, NEDD4L and ITCH leads to relocalization of CC these proteins to exosomes and eventually to exosomal secretion (By CC similarity). Interacts with U2SURP (By similarity). Interacts with CC SLC11A2/DMT1 (PubMed:18776082, PubMed:19706893). Interacts with PTEN CC (PubMed:20534535, PubMed:25801959). May interact with phosphorylated CC EGFR (PubMed:20534535). Interacts with BRAT1 (PubMed:25631046). CC Interacts with KCNH2 (PubMed:26363003). Interacts with MAVS CC (PubMed:23087404). Part of a complex containing ITCH, NDFIP1 and MAP3K7 CC (By similarity). Interacts (via N-terminus) with UBE2L3; the CC interaction mediates recruitment of UBE2L3 to ITCH (PubMed:25632008). CC {ECO:0000250|UniProtKB:Q8R0W6, ECO:0000269|PubMed:18776082, CC ECO:0000269|PubMed:19706893, ECO:0000269|PubMed:20534535, CC ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:25631046, CC ECO:0000269|PubMed:25632008, ECO:0000269|PubMed:25801959, CC ECO:0000269|PubMed:26363003}. CC -!- INTERACTION: CC Q9BT67; P49281: SLC11A2; NbExp=2; IntAct=EBI-11732799, EBI-4319335; CC Q9BT67; P07919: UQCRH; NbExp=3; IntAct=EBI-11732799, EBI-1224427; CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000269|PubMed:20534535}; CC Multi-pass membrane protein {ECO:0000269|PubMed:20534535}. Golgi CC apparatus membrane {ECO:0000269|PubMed:26363003}. Synapse, synaptosome CC {ECO:0000250|UniProtKB:Q8R0W6}. Cell projection, dendrite CC {ECO:0000250|UniProtKB:Q5U2S1}. Secreted {ECO:0000269|PubMed:18819914}. CC Note=Detected in exosomes and secreted via the exosomal pathway CC (PubMed:18819914). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9BT67-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BT67-2; Sequence=VSP_016474, VSP_016475; CC -!- TISSUE SPECIFICITY: Widely expressed. Higher levels are detected in CC cerebellum, pituitary, thalamus, kidney, liver, testis, salivary glands CC and placenta. Also expressed in fetal brain, kidney and lung. CC {ECO:0000269|PubMed:11748237}. CC -!- INDUCTION: Increased protein expression in neuronal cells in response CC to Co(2+) or Fe(2+) ions. {ECO:0000269|PubMed:19706893}. CC -!- DOMAIN: The PPxY motifs are required for E3 ubiquitin-protein ligase CC binding and activation and for ubiquitination. CC {ECO:0000269|PubMed:23087404}. CC -!- PTM: Ubiquitinated by NEDD4 and ITCH; mono-, di- and polyubiquitinated CC forms are detected. Ubiquitination regulates its degradation. CC {ECO:0000269|PubMed:19343052}. 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. {ECO:0000269|PubMed:20534535}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY192728; AAP13460.1; -; mRNA. DR EMBL; AB097010; BAC77363.1; -; mRNA. DR EMBL; AB097037; BAC77390.1; -; mRNA. DR EMBL; AK075495; BAC11652.1; -; mRNA. DR EMBL; AK075524; BAC11670.1; -; mRNA. DR EMBL; AK315481; BAG37865.1; -; mRNA. DR EMBL; CH471062; EAW61888.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61889.1; -; Genomic_DNA. DR EMBL; BC004317; AAH04317.1; -; mRNA. DR EMBL; AL832993; CAH56294.1; -; mRNA. DR CCDS; CCDS4273.1; -. [Q9BT67-1] DR RefSeq; NP_085048.1; NM_030571.3. [Q9BT67-1] DR AlphaFoldDB; Q9BT67; -. DR BioGRID; 123296; 111. DR CORUM; Q9BT67; -. DR DIP; DIP-48958N; -. DR IntAct; Q9BT67; 38. DR MINT; Q9BT67; -. DR STRING; 9606.ENSP00000253814; -. DR iPTMnet; Q9BT67; -. DR PhosphoSitePlus; Q9BT67; -. DR SwissPalm; Q9BT67; -. DR BioMuta; NDFIP1; -. DR DMDM; 74733098; -. DR EPD; Q9BT67; -. DR jPOST; Q9BT67; -. DR MassIVE; Q9BT67; -. DR MaxQB; Q9BT67; -. DR PaxDb; 9606-ENSP00000253814; -. DR PeptideAtlas; Q9BT67; -. DR ProteomicsDB; 78953; -. [Q9BT67-1] DR ProteomicsDB; 78954; -. [Q9BT67-2] DR Pumba; Q9BT67; -. DR Antibodypedia; 2434; 233 antibodies from 32 providers. DR DNASU; 80762; -. DR Ensembl; ENST00000253814.6; ENSP00000253814.3; ENSG00000131507.11. [Q9BT67-1] DR GeneID; 80762; -. DR KEGG; hsa:80762; -. DR MANE-Select; ENST00000253814.6; ENSP00000253814.3; NM_030571.4; NP_085048.1. DR UCSC; uc003lmi.5; human. [Q9BT67-1] DR AGR; HGNC:17592; -. DR CTD; 80762; -. DR DisGeNET; 80762; -. DR GeneCards; NDFIP1; -. DR HGNC; HGNC:17592; NDFIP1. DR HPA; ENSG00000131507; Low tissue specificity. DR MIM; 612050; gene. DR neXtProt; NX_Q9BT67; -. DR OpenTargets; ENSG00000131507; -. DR PharmGKB; PA134943402; -. DR VEuPathDB; HostDB:ENSG00000131507; -. DR eggNOG; KOG4812; Eukaryota. DR GeneTree; ENSGT00390000012721; -. DR HOGENOM; CLU_074980_2_0_1; -. DR InParanoid; Q9BT67; -. DR OMA; FASHENS; -. DR OrthoDB; 4642592at2759; -. DR PhylomeDB; Q9BT67; -. DR TreeFam; TF324911; -. DR PathwayCommons; Q9BT67; -. DR SignaLink; Q9BT67; -. DR SIGNOR; Q9BT67; -. DR BioGRID-ORCS; 80762; 11 hits in 1155 CRISPR screens. DR ChiTaRS; NDFIP1; human. DR GenomeRNAi; 80762; -. DR Pharos; Q9BT67; Tbio. DR PRO; PR:Q9BT67; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q9BT67; Protein. DR Bgee; ENSG00000131507; Expressed in Brodmann (1909) area 23 and 211 other cell types or tissues. DR GO; GO:0005938; C:cell cortex; IEA:Ensembl. 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; IBA:GO_Central. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell. DR GO; GO:0050699; F:WW domain binding; IBA:GO_Central. DR GO; GO:0035739; P:CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl. DR GO; GO:0006879; P:intracellular iron ion homeostasis; IMP:UniProtKB. 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; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB. DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl. DR GO; GO:0032713; P:negative regulation of interleukin-4 production; IEA:Ensembl. DR GO; GO:0048294; P:negative regulation of isotype switching to IgE isotypes; IEA:Ensembl. DR GO; GO:0051224; P:negative regulation of protein transport; IMP:UniProtKB. DR GO; GO:0032410; P:negative regulation of transporter activity; IMP:UniProtKB. DR GO; GO:0002829; P:negative regulation of type 2 immune response; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; HMP:UniProtKB. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB. DR GO; GO:0048302; P:regulation of isotype switching to IgG isotypes; IEA:Ensembl. DR GO; GO:0045619; P:regulation of lymphocyte differentiation; IEA:Ensembl. DR GO; GO:0002761; P:regulation of myeloid leukocyte differentiation; IEA:Ensembl. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR GO; GO:0007034; P:vacuolar transport; IEA:InterPro. DR CDD; cd22305; NDFIP1; 1. DR InterPro; IPR019325; NEDD4/Bsd2. DR PANTHER; PTHR13396; NEDD4 FAMILY INTERACTING PROTEIN 1/2; 1. DR PANTHER; PTHR13396:SF3; NEDD4 FAMILY-INTERACTING PROTEIN 1; 1. DR Pfam; PF10176; DUF2370; 1. DR Genevisible; Q9BT67; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Cell projection; Endosome; KW Golgi apparatus; Membrane; Reference proteome; Repeat; Secreted; Synapse; KW Synaptosome; Transmembrane; Transmembrane helix; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22223895" FT CHAIN 2..221 FT /note="NEDD4 family-interacting protein 1" FT /id="PRO_0000076269" 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:0000250|UniProtKB:Q8R0W6" FT REGION 18..45 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 42..76 FT /note="Interaction with ITCH" FT /evidence="ECO:0000250|UniProtKB:Q8R0W6" 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:0007744|PubMed:22223895" FT VAR_SEQ 76..153 FT /note="YDEAERTKAEATIPLVPGRDEDFVGRDDFDDADQLRIGNDGIFMLTFFMAFL FT FNWIGFFLSFCLTTSAAGRYGAISGF -> CFYDISHLIFFIFYLRNMKKKYTKMVKLL FT HKSAPAQSDSCKCPFICCVCISRISIGSRSGYQYIMHRSVGCLKAKQEN (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_016474" FT VAR_SEQ 154..221 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_016475" FT MUTAGEN 41..42 FT /note="PY->AG: Loss of phosphorylation; when associated FT with 66-S-Y-67 and 75-S-Y-76. Greatly decreases FT NEDD4-binding; when associated with 66-S-Y-67 and FT 75-S-Y-76. No effect on PTEN-binding; when associated with FT 66-S-Y-67 and 75-S-Y-76." FT /evidence="ECO:0000269|PubMed:20534535" FT MUTAGEN 66..67 FT /note="SY->AG: Loss of phosphorylation; when associated FT with 41-P-Y-42 and 75-S-Y-76. Greatly decreases FT NEDD4-binding; when associated with 41-P-Y-42 and FT 75-S-Y-76. No effect on PTEN-binding; when associated with FT 41-P-Y-42 and 75-S-Y-76." FT /evidence="ECO:0000269|PubMed:20534535" FT MUTAGEN 75..76 FT /note="SY->AG: Loss of phosphorylation; when associated FT with 41-P-Y-42 and 66-S-Y-67. Greatly decreases FT NEDD4-binding; when associated with 41-P-Y-42 and FT 66-S-Y-67. No effect on PTEN-binding; when associated with FT 41-P-Y-42 and 66-S-Y-67." FT /evidence="ECO:0000269|PubMed:20534535" FT CONFLICT 20 FT /note="Q -> W (in Ref. 4; BAC11670)" FT /evidence="ECO:0000305" FT CONFLICT 104 FT /note="F -> L (in Ref. 4; BAC11670)" FT /evidence="ECO:0000305" SQ SEQUENCE 221 AA; 24899 MW; 526A579D7B32FCA4 CRC64; MALALAALAA VEPACGSRYQ QLQNEEESGE PEQAAGDAPP PYSSISAESA AYFDYKDESG FPKPPSYNVA TTLPSYDEAE RTKAEATIPL VPGRDEDFVG RDDFDDADQL RIGNDGIFML TFFMAFLFNW IGFFLSFCLT TSAAGRYGAI SGFGLSLIKW ILIVRFSTYF PGYFDGQYWL WWVFLVLGFL LFLRGFINYA KVRKMPETFS NLPRTRVLFI Y //