NFIP1_HUMAN
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 03-AUG-2022, entry version 146.
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}.
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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; 106.
DR CORUM; Q9BT67; -.
DR DIP; DIP-48958N; -.
DR IntAct; Q9BT67; 36.
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; Q9BT67; -.
DR PeptideAtlas; Q9BT67; -.
DR PRIDE; Q9BT67; -.
DR ProteomicsDB; 78953; -. [Q9BT67-1]
DR ProteomicsDB; 78954; -. [Q9BT67-2]
DR Antibodypedia; 2434; 211 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 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; TGRQPHH; -.
DR OrthoDB; 1495850at2759; -.
DR PhylomeDB; Q9BT67; -.
DR TreeFam; TF324911; -.
DR PathwayCommons; Q9BT67; -.
DR SignaLink; Q9BT67; -.
DR SIGNOR; Q9BT67; -.
DR BioGRID-ORCS; 80762; 10 hits in 1077 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 209 other tissues.
DR Genevisible; Q9BT67; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:cellular 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 I-kappaB kinase/NF-kappaB signaling; 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 InterPro; IPR019325; NEDD4/Bsd2.
DR PANTHER; PTHR13396; PTHR13396; 1.
DR Pfam; PF10176; DUF2370; 1.
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 NEDD4-
FT binding; when associated with 66-S-Y-67 and 75-S-Y-76. No
FT effect on PTEN-binding; when associated with 66-S-Y-67 and
FT 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 NEDD4-
FT binding; when associated with 41-P-Y-42 and 75-S-Y-76. No
FT effect on PTEN-binding; when associated with 41-P-Y-42 and
FT 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 NEDD4-
FT binding; when associated with 41-P-Y-42 and 66-S-Y-67. No
FT effect on PTEN-binding; when associated with 41-P-Y-42 and
FT 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
