NUMB_HUMAN
ID NUMB_HUMAN Reviewed; 651 AA.
AC P49757; B1P2N5; B1P2N6; B1P2N7; B1P2N8; B1P2N9; B4E2B1; Q6NUQ7; Q86SY1;
AC Q8WW73; Q9UBG1; Q9UEQ4; Q9UKE8; Q9UKE9; Q9UKF0; Q9UQJ4;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Protein numb homolog;
DE Short=h-Numb;
DE AltName: Full=Protein S171;
GN Name=NUMB {ECO:0000312|HGNC:HGNC:8060};
GN Synonyms=C14orf41 {ECO:0000312|HGNC:HGNC:8060};
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 2).
RX PubMed=9303539; DOI=10.1101/gad.11.17.2239;
RA Salcini A.E., Confalonieri S., Doria M., Santolini E., Tassi E.,
RA Minenkova O., Cesareni G., Pelicci P.G., Di Fiore P.P.;
RT "Binding specificity and in vivo targets of the EH domain, a novel protein-
RT protein interaction module.";
RL Genes Dev. 11:2239-2249(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
RC TISSUE=Neuron;
RX PubMed=10468633; DOI=10.1073/pnas.96.18.10472;
RA Verdi J.M., Bashirullah A., Goldhawk D.E., Kubu C.J., Jamali M.,
RA Meakin S.O., Lipshitz H.D.;
RT "Distinct human NUMB isoforms regulate differentiation vs. proliferation in
RT the neuronal lineage.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:10472-10476(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5; 6; 7; 8 AND 9), AND ALTERNATIVE
RP SPLICING.
RC TISSUE=Placenta;
RX PubMed=21486681; DOI=10.1016/j.placenta.2011.03.008;
RA Haider M., Qiu Q., Bani-Yaghoub M., Tsang B.K., Gruslin A.;
RT "Characterization and role of NUMB in the human extravillous
RT trophopblast.";
RL Placenta 32:441-449(2011).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Ye Q., Jiang K., Han W., Moore M.A.S.;
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 9).
RC TISSUE=Brain, and Trachea;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [7]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-256 (ISOFORMS 3/4).
RC TISSUE=Liver, and Testis;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-529 (ISOFORM 1).
RC TISSUE=Cervix carcinoma;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 79-651 (ISOFORMS 2/4).
RC TISSUE=Fetal brain;
RA Rowen L., Madan A., Qin S., Abbasi N., Dors M., Ratcliffe A., Madan A.,
RA Dickhoff R., Shaffer T., James R., Lasky S., Hood L.;
RT "Complete sequence of the gene for presenilin 1.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 517-651.
RC TISSUE=Brain;
RX PubMed=7596406; DOI=10.1038/375754a0;
RA Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M.,
RA Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L., Foncin J.-F.,
RA Bruni A.C., Montesi M.P., Sorbi S., Rainero I., Pinessi L., Nee L.,
RA Chumakov I., Pollen D., Brookes A., Sanseau P., Polinsky R.J., Wasco W.,
RA da Silva H.A.R., Haines J.L., Pericak-Vance M.A., Tanzi R.E., Roses A.D.,
RA Fraser P.E., Rommens J.M., St George-Hyslop P.H.;
RT "Cloning of a gene bearing missense mutations in early-onset familial
RT Alzheimer's disease.";
RL Nature 375:754-760(1995).
RN [12]
RP INTERACTION WITH SIAH1, AND DEGRADATION.
RX PubMed=11752454; DOI=10.1073/pnas.261571998;
RA Susini L., Passer B.J., Amzallag-Elbaz N., Juven-Gershon T., Prieur S.,
RA Privat N., Tuynder M., Gendron M.-C., Israeel A., Amson R., Oren M.,
RA Telerman A.;
RT "Siah-1 binds and regulates the function of Numb.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:15067-15072(2001).
RN [13]
RP INTERACTION WITH RALBP1.
RX PubMed=12775724; DOI=10.1074/jbc.m302191200;
RA Rosse C., L'Hoste S., Offner N., Picard A., Camonis J.;
RT "RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to
RT phosphorylate epsin during the switch off of endocytosis in mitosis.";
RL J. Biol. Chem. 278:30597-30604(2003).
RN [14]
RP INTERACTION WITH DUOXA1.
RX PubMed=14670962; DOI=10.1074/jbc.m311733200;
RA Qin H., Percival-Smith A., Li C., Jia C.Y.H., Gloor G., Li S.S.-C.;
RT "A novel transmembrane protein recruits numb to the plasma membrane during
RT asymmetric cell division.";
RL J. Biol. Chem. 279:11304-11312(2004).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-634, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-244, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP FUNCTION, INTERACTION WITH AAK1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP THR-102, AND MUTAGENESIS OF THR-102.
RX PubMed=18657069; DOI=10.1111/j.1600-0854.2008.00790.x;
RA Sorensen E.B., Conner S.D.;
RT "AAK1 regulates Numb function at an early step in clathrin-mediated
RT endocytosis.";
RL Traffic 9:1791-1800(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194; SER-425; THR-436;
RP SER-438 AND SER-634, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Regulates clathrin-mediated receptor endocytosis
CC (PubMed:18657069). Plays a role in the process of neurogenesis (By
CC similarity). Required throughout embryonic neurogenesis to maintain
CC neural progenitor cells, also called radial glial cells (RGCs), by
CC allowing their daughter cells to choose progenitor over neuronal cell
CC fate (By similarity). Not required for the proliferation of neural
CC progenitor cells before the onset of neurogenesis. Also involved
CC postnatally in the subventricular zone (SVZ) neurogenesis by regulating
CC SVZ neuroblasts survival and ependymal wall integrity (By similarity).
CC May also mediate local repair of brain ventricular wall damage (By
CC similarity). {ECO:0000250|UniProtKB:Q9QZS3,
CC ECO:0000269|PubMed:18657069}.
CC -!- SUBUNIT: Interacts with SIAH1 (PubMed:11752454). Interacts with LNX (By
CC similarity). Interacts with CDH1 (By similarity). Interacts with TFAP2A
CC and TFAP2B (By similarity). Interacts with RALBP1 in a complex also
CC containing EPN1 and TFAP2A during interphase and mitosis
CC (PubMed:12775724). Interacts with AAK1 (PubMed:18657069). May interact
CC with DUOXA1 (PubMed:14670962). {ECO:0000250|UniProtKB:Q2LC84,
CC ECO:0000250|UniProtKB:Q9QZS3, ECO:0000269|PubMed:11752454,
CC ECO:0000269|PubMed:12775724, ECO:0000269|PubMed:14670962,
CC ECO:0000269|PubMed:18657069}.
CC -!- INTERACTION:
CC P49757; P35222: CTNNB1; NbExp=2; IntAct=EBI-915016, EBI-491549;
CC P49757; P42566: EPS15; NbExp=4; IntAct=EBI-915016, EBI-396684;
CC P49757; Q00987: MDM2; NbExp=9; IntAct=EBI-915016, EBI-389668;
CC P49757; Q96D71: REPS1; NbExp=3; IntAct=EBI-915016, EBI-1171195;
CC P49757; P04637: TP53; NbExp=5; IntAct=EBI-915016, EBI-366083;
CC P49757-1; Q05513: PRKCZ; NbExp=4; IntAct=EBI-7199607, EBI-295351;
CC P49757-3; P35222: CTNNB1; NbExp=3; IntAct=EBI-10692196, EBI-491549;
CC P49757-8; P05067: APP; NbExp=3; IntAct=EBI-25937715, EBI-77613;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18657069};
CC Peripheral membrane protein {ECO:0000305|PubMed:18657069}; Cytoplasmic
CC side {ECO:0000305|PubMed:18657069}. Endosome membrane
CC {ECO:0000269|PubMed:18657069}; Peripheral membrane protein
CC {ECO:0000305|PubMed:18657069}; Cytoplasmic side
CC {ECO:0000305|PubMed:18657069}. Note=Localizes to perinuclear endosomes
CC in an AAK1-dependent manner. {ECO:0000269|PubMed:18657069}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Name=1; Synonyms=p72;
CC IsoId=P49757-1; Sequence=Displayed;
CC Name=2; Synonyms=p66;
CC IsoId=P49757-2; Sequence=VSP_004349;
CC Name=3; Synonyms=p71;
CC IsoId=P49757-3; Sequence=VSP_004348;
CC Name=4; Synonyms=p65;
CC IsoId=P49757-4; Sequence=VSP_004348, VSP_004349;
CC Name=5;
CC IsoId=P49757-5; Sequence=VSP_047756, VSP_004349;
CC Name=6;
CC IsoId=P49757-6; Sequence=VSP_004348, VSP_047756, VSP_004349;
CC Name=7;
CC IsoId=P49757-7; Sequence=VSP_047756, VSP_053763, VSP_004349;
CC Name=8;
CC IsoId=P49757-8; Sequence=VSP_004348, VSP_047756, VSP_053763,
CC VSP_004349;
CC Name=9;
CC IsoId=P49757-9; Sequence=VSP_053745, VSP_004349;
CC -!- PTM: Phosphorylated on Ser-276 and Ser-295 by CaMK1. {ECO:0000250}.
CC -!- PTM: Isoform 1 and isoform 2 are ubiquitinated by LNX leading to their
CC subsequent proteasomal degradation (By similarity). Ubiquitinated;
CC mediated by SIAH1 and leading to its subsequent proteasomal
CC degradation. {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH20788.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NUMBID43702ch14q24.html";
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DR EMBL; AF015040; AAD01548.1; -; mRNA.
DR EMBL; AF171938; AAD54279.1; -; mRNA.
DR EMBL; AF171939; AAD54280.1; -; mRNA.
DR EMBL; AF171940; AAD54281.1; -; mRNA.
DR EMBL; AF171941; AAD54282.1; -; mRNA.
DR EMBL; EU265734; ABY89090.1; -; mRNA.
DR EMBL; EU265735; ABY89091.1; -; mRNA.
DR EMBL; EU265736; ABY89092.1; -; mRNA.
DR EMBL; EU265737; ABY89093.1; -; mRNA.
DR EMBL; EU265738; ABY89094.1; -; mRNA.
DR EMBL; AF108092; AAD27959.1; -; mRNA.
DR EMBL; AK294591; BAG57779.1; -; mRNA.
DR EMBL; AK304193; BAG65073.1; -; mRNA.
DR EMBL; AC004846; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005280; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391733; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW81106.1; -; Genomic_DNA.
DR EMBL; BC020788; AAH20788.1; ALT_SEQ; mRNA.
DR EMBL; BC068476; AAH68476.1; -; mRNA.
DR EMBL; BX248073; CAD62362.1; -; mRNA.
DR EMBL; AF109907; AAC97962.1; -; Genomic_DNA.
DR EMBL; L40393; AAC42000.1; -; mRNA.
DR CCDS; CCDS32115.1; -. [P49757-2]
DR CCDS; CCDS32116.1; -. [P49757-1]
DR CCDS; CCDS55927.1; -. [P49757-4]
DR CCDS; CCDS9814.1; -. [P49757-3]
DR RefSeq; NP_001005743.1; NM_001005743.1. [P49757-1]
DR RefSeq; NP_001005744.1; NM_001005744.1. [P49757-2]
DR RefSeq; NP_001005745.1; NM_001005745.1. [P49757-4]
DR RefSeq; NP_001307043.1; NM_001320114.1. [P49757-2]
DR RefSeq; NP_003735.3; NM_003744.5. [P49757-3]
DR PDB; 5NJJ; X-ray; 2.70 A; A/B/C/D=20-175.
DR PDB; 5NJK; X-ray; 3.13 A; A/B/C/D/E/F=20-175.
DR PDBsum; 5NJJ; -.
DR PDBsum; 5NJK; -.
DR AlphaFoldDB; P49757; -.
DR SMR; P49757; -.
DR BioGRID; 114202; 176.
DR CORUM; P49757; -.
DR DIP; DIP-37981N; -.
DR ELM; P49757; -.
DR IntAct; P49757; 66.
DR MINT; P49757; -.
DR STRING; 9606.ENSP00000451300; -.
DR GlyGen; P49757; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P49757; -.
DR MetOSite; P49757; -.
DR PhosphoSitePlus; P49757; -.
DR SwissPalm; P49757; -.
DR BioMuta; NUMB; -.
DR DMDM; 14195675; -.
DR EPD; P49757; -.
DR jPOST; P49757; -.
DR MassIVE; P49757; -.
DR MaxQB; P49757; -.
DR PaxDb; P49757; -.
DR PeptideAtlas; P49757; -.
DR PRIDE; P49757; -.
DR ProteomicsDB; 3393; -.
DR ProteomicsDB; 3394; -.
DR ProteomicsDB; 3395; -.
DR ProteomicsDB; 3396; -.
DR ProteomicsDB; 56075; -. [P49757-1]
DR ProteomicsDB; 56076; -. [P49757-2]
DR ProteomicsDB; 56077; -. [P49757-3]
DR ProteomicsDB; 56078; -. [P49757-4]
DR Antibodypedia; 131; 900 antibodies from 43 providers.
DR DNASU; 8650; -.
DR Ensembl; ENST00000355058.7; ENSP00000347169.3; ENSG00000133961.21. [P49757-1]
DR Ensembl; ENST00000356296.8; ENSP00000348644.4; ENSG00000133961.21. [P49757-2]
DR Ensembl; ENST00000359560.7; ENSP00000352563.3; ENSG00000133961.21. [P49757-3]
DR Ensembl; ENST00000535282.5; ENSP00000441258.2; ENSG00000133961.21. [P49757-2]
DR Ensembl; ENST00000544991.7; ENSP00000446001.3; ENSG00000133961.21. [P49757-7]
DR Ensembl; ENST00000554521.6; ENSP00000450817.2; ENSG00000133961.21. [P49757-8]
DR Ensembl; ENST00000554546.5; ENSP00000452416.1; ENSG00000133961.21. [P49757-4]
DR Ensembl; ENST00000555238.6; ENSP00000451300.1; ENSG00000133961.21. [P49757-1]
DR Ensembl; ENST00000555394.5; ENSP00000451625.1; ENSG00000133961.21. [P49757-2]
DR Ensembl; ENST00000555738.6; ENSP00000452069.2; ENSG00000133961.21. [P49757-6]
DR Ensembl; ENST00000557597.5; ENSP00000451117.1; ENSG00000133961.21. [P49757-3]
DR Ensembl; ENST00000559312.5; ENSP00000452888.1; ENSG00000133961.21. [P49757-7]
DR Ensembl; ENST00000560335.5; ENSP00000453209.1; ENSG00000133961.21. [P49757-5]
DR GeneID; 8650; -.
DR KEGG; hsa:8650; -.
DR MANE-Select; ENST00000555238.6; ENSP00000451300.1; NM_001005743.2; NP_001005743.1.
DR UCSC; uc001xny.2; human. [P49757-1]
DR CTD; 8650; -.
DR DisGeNET; 8650; -.
DR GeneCards; NUMB; -.
DR HGNC; HGNC:8060; NUMB.
DR HPA; ENSG00000133961; Low tissue specificity.
DR MIM; 603728; gene.
DR neXtProt; NX_P49757; -.
DR OpenTargets; ENSG00000133961; -.
DR PharmGKB; PA31845; -.
DR VEuPathDB; HostDB:ENSG00000133961; -.
DR eggNOG; KOG3537; Eukaryota.
DR GeneTree; ENSGT00940000156005; -.
DR HOGENOM; CLU_031797_1_1_1; -.
DR InParanoid; P49757; -.
DR OMA; CSFPVKX; -.
DR PhylomeDB; P49757; -.
DR TreeFam; TF314159; -.
DR PathwayCommons; P49757; -.
DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR Reactome; R-HSA-437239; Recycling pathway of L1.
DR Reactome; R-HSA-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR SignaLink; P49757; -.
DR SIGNOR; P49757; -.
DR BioGRID-ORCS; 8650; 15 hits in 1078 CRISPR screens.
DR ChiTaRS; NUMB; human.
DR GeneWiki; NUMB_(gene); -.
DR GenomeRNAi; 8650; -.
DR Pharos; P49757; Tbio.
DR PRO; PR:P49757; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P49757; protein.
DR Bgee; ENSG00000133961; Expressed in monocyte and 197 other tissues.
DR ExpressionAtlas; P49757; baseline and differential.
DR Genevisible; P49757; HS.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:Ensembl.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; IEA:Ensembl.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IEA:Ensembl.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045294; F:alpha-catenin binding; IEA:Ensembl.
DR GO; GO:0008013; F:beta-catenin binding; IEA:Ensembl.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0034332; P:adherens junction organization; IEA:Ensembl.
DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR GO; GO:0021670; P:lateral ventricle development; ISS:UniProtKB.
DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0021849; P:neuroblast division in subventricular zone; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0050769; P:positive regulation of neurogenesis; ISS:UniProtKB.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IEA:Ensembl.
DR DisProt; DP01130; -.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR016698; Numb/numb-like.
DR InterPro; IPR010449; Numb_domain.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR PANTHER; PTHR47368; PTHR47368; 1.
DR Pfam; PF06311; NumbF; 1.
DR Pfam; PF00640; PID; 1.
DR PIRSF; PIRSF017607; Numb/numb-like; 1.
DR SMART; SM00462; PTB; 1.
DR PROSITE; PS01179; PID; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Developmental protein;
KW Endosome; Membrane; Neurogenesis; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..651
FT /note="Protein numb homolog"
FT /id="PRO_0000058001"
FT DOMAIN 33..193
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 228..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 419..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 623..651
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 231..257
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 463..477
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 624..644
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 102
FT /note="Phosphothreonine; by AAK1"
FT /evidence="ECO:0000305|PubMed:18657069"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 243
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZS3"
FT MOD_RES 244
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 276
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000250|UniProtKB:Q2LC84"
FT MOD_RES 295
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000250|UniProtKB:Q2LC84"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 436
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 438
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 634
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..254
FT /note="Missing (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:21486681"
FT /id="VSP_053745"
FT VAR_SEQ 68..78
FT /note="Missing (in isoform 3, isoform 4, isoform 6 and
FT isoform 8)"
FT /evidence="ECO:0000303|PubMed:10468633,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:21486681"
FT /id="VSP_004348"
FT VAR_SEQ 219..316
FT /note="Missing (in isoform 5, isoform 6, isoform 7 and
FT isoform 8)"
FT /evidence="ECO:0000303|PubMed:21486681"
FT /id="VSP_047756"
FT VAR_SEQ 317..365
FT /note="Missing (in isoform 7 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:21486681"
FT /id="VSP_053763"
FT VAR_SEQ 366..413
FT /note="Missing (in isoform 2, isoform 4, isoform 5, isoform
FT 6, isoform 7, isoform 8 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:10468633,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:21486681, ECO:0000303|PubMed:9303539,
FT ECO:0000303|Ref.4"
FT /id="VSP_004349"
FT VARIANT 387
FT /note="V -> I (in dbSNP:rs17182272)"
FT /id="VAR_051249"
FT VARIANT 595
FT /note="G -> D (in dbSNP:rs17781919)"
FT /id="VAR_051250"
FT MUTAGEN 102
FT /note="T->A: Loss of AAK1-mediated phosphorylation."
FT /evidence="ECO:0000269|PubMed:18657069"
FT CONFLICT 31
FT /note="G -> S (in Ref. 4; AAD27959)"
FT /evidence="ECO:0000305"
FT CONFLICT 68
FT /note="E -> Q (in Ref. 4; AAD27959)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="G -> R (in Ref. 4; AAD27959)"
FT /evidence="ECO:0000305"
FT CONFLICT 450
FT /note="S -> N (in Ref. 4; AAD27959)"
FT /evidence="ECO:0000305"
FT CONFLICT 533
FT /note="Q -> K (in Ref. 8; AAH68476)"
FT /evidence="ECO:0000305"
FT HELIX 28..33
FT /evidence="ECO:0007829|PDB:5NJJ"
FT STRAND 38..48
FT /evidence="ECO:0007829|PDB:5NJJ"
FT STRAND 50..53
FT /evidence="ECO:0007829|PDB:5NJJ"
FT HELIX 55..71
FT /evidence="ECO:0007829|PDB:5NJJ"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:5NJJ"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:5NJK"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:5NJJ"
FT STRAND 92..99
FT /evidence="ECO:0007829|PDB:5NJJ"
FT TURN 100..102
FT /evidence="ECO:0007829|PDB:5NJJ"
FT STRAND 105..110
FT /evidence="ECO:0007829|PDB:5NJJ"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:5NJJ"
FT STRAND 114..119
FT /evidence="ECO:0007829|PDB:5NJJ"
FT STRAND 126..133
FT /evidence="ECO:0007829|PDB:5NJJ"
FT TURN 134..137
FT /evidence="ECO:0007829|PDB:5NJJ"
FT STRAND 138..149
FT /evidence="ECO:0007829|PDB:5NJJ"
FT HELIX 151..168
FT /evidence="ECO:0007829|PDB:5NJJ"
SQ SEQUENCE 651 AA; 70804 MW; 5B590BE49A74FCF2 CRC64;
MNKLRQSFRR KKDVYVPEAS RPHQWQTDEE GVRTGKCSFP VKYLGHVEVD ESRGMHICED
AVKRLKAERK FFKGFFGKTG KKAVKAVLWV SADGLRVVDE KTKDLIVDQT IEKVSFCAPD
RNFDRAFSYI CRDGTTRRWI CHCFMAVKDT GERLSHAVGC AFAACLERKQ KREKECGVTA
TFDASRTTFT REGSFRVTTA TEQAEREEIM KQMQDAKKAE TDKIVVGSSV APGNTAPSPS
SPTSPTSDAT TSLEMNNPHA IPRRHAPIEQ LARQGSFRGF PALSQKMSPF KRQLSLRINE
LPSTMQRKTD FPIKNAVPEV EGEAESISSL CSQITNAFST PEDPFSSAPM TKPVTVVAPQ
SPTFQANGTD SAFHVLAKPA HTALAPVAMP VRETNPWAHA PDAANKEIAA TCSGTEWGQS
SGAASPGLFQ AGHRRTPSEA DRWLEEVSKS VRAQQPQASA APLQPVLQPP PPTAISQPAS
PFQGNAFLTS QPVPVGVVPA LQPAFVPAQS YPVANGMPYP APNVPVVGIT PSQMVANVFG
TAGHPQAAHP HQSPSLVRQQ TFPHYEASSA TTSPFFKPPA QHLNGSAAFN GVDDGRLASA
DRHTEVPTGT CPVDPFEAQW AALENKSKQR TNPSPTNPFS SDLQKTFEIE L
