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 02-SEP-2026, entry version 207. 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; P00533: EGFR; NbExp=2; IntAct=EBI-915016, EBI-297353; CC P49757; P42566: EPS15; NbExp=4; IntAct=EBI-915016, EBI-396684; CC P49757; Q00987: MDM2; NbExp=7; 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="https://atlasgeneticsoncology.org/gene/43702/NUMB"; 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; 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_001005743.2. [P49757-1] DR RefSeq; NP_001005744.1; NM_001005744.2. [P49757-2] DR RefSeq; NP_001005745.1; NM_001005745.2. [P49757-4] DR RefSeq; NP_001307043.1; NM_001320114.2. [P49757-2] DR RefSeq; NP_003735.3; NM_003744.6. [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 AlphaFoldDB; P49757; -. DR SMR; P49757; -. DR BioGRID; 114202; 248. DR CORUM; P49757; -. DR DIP; DIP-37981N; -. DR ELM; P49757; -. DR FunCoup; P49757; 1796. DR IntAct; P49757; 109. DR MINT; P49757; -. DR NDEx; IQUERY-CP-NUMB; 8 NDEx IQuery Curated Pathways. 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 jPOST; P49757; -. DR MassIVE; P49757; -. DR PaxDb; 9606-ENSP00000451300; -. DR PeptideAtlas; 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 Pumba; P49757; -. DR Antibodypedia; 131; 923 antibodies from 45 providers. DR DNASU; 8650; -. DR Ensembl; ENST00000355058.7; ENSP00000347169.3; ENSG00000133961.23. [P49757-1] DR Ensembl; ENST00000356296.8; ENSP00000348644.4; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000359560.7; ENSP00000352563.3; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000535282.5; ENSP00000441258.2; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000544991.7; ENSP00000446001.3; ENSG00000133961.23. [P49757-7] DR Ensembl; ENST00000554521.6; ENSP00000450817.2; ENSG00000133961.23. [P49757-8] DR Ensembl; ENST00000554546.5; ENSP00000452416.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000555238.6; ENSP00000451300.1; ENSG00000133961.23. [P49757-1] DR Ensembl; ENST00000555394.5; ENSP00000451625.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000555738.6; ENSP00000452069.2; ENSG00000133961.23. [P49757-6] DR Ensembl; ENST00000557597.5; ENSP00000451117.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000559312.5; ENSP00000452888.1; ENSG00000133961.23. [P49757-7] DR Ensembl; ENST00000560335.5; ENSP00000453209.1; ENSG00000133961.23. [P49757-5] DR Ensembl; ENST00000863595.1; ENSP00000533654.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863597.1; ENSP00000533656.1; ENSG00000133961.23. [P49757-7] DR Ensembl; ENST00000863598.1; ENSP00000533657.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863599.1; ENSP00000533658.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863600.1; ENSP00000533659.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863601.1; ENSP00000533660.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000863602.1; ENSP00000533661.1; ENSG00000133961.23. [P49757-5] DR Ensembl; ENST00000863603.1; ENSP00000533662.1; ENSG00000133961.23. [P49757-6] DR Ensembl; ENST00000863606.1; ENSP00000533665.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863607.1; ENSP00000533666.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000863608.1; ENSP00000533667.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000863610.1; ENSP00000533669.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863613.1; ENSP00000533672.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000863614.1; ENSP00000533673.1; ENSG00000133961.23. [P49757-1] DR Ensembl; ENST00000863615.1; ENSP00000533674.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000863617.1; ENSP00000533676.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000863619.1; ENSP00000533678.1; ENSG00000133961.23. [P49757-8] DR Ensembl; ENST00000863624.1; ENSP00000533683.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000863625.1; ENSP00000533684.1; ENSG00000133961.23. [P49757-6] DR Ensembl; ENST00000863627.1; ENSP00000533686.1; ENSG00000133961.23. [P49757-1] DR Ensembl; ENST00000863638.1; ENSP00000533697.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000863644.1; ENSP00000533703.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000863645.1; ENSP00000533704.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000863646.1; ENSP00000533705.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863647.1; ENSP00000533706.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000863648.1; ENSP00000533707.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000863651.1; ENSP00000533710.1; ENSG00000133961.23. [P49757-1] DR Ensembl; ENST00000863652.1; ENSP00000533711.1; ENSG00000133961.23. [P49757-1] DR Ensembl; ENST00000863653.1; ENSP00000533712.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000863656.1; ENSP00000533715.1; ENSG00000133961.23. [P49757-1] DR Ensembl; ENST00000863661.1; ENSP00000533720.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000863663.1; ENSP00000533722.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863665.1; ENSP00000533724.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863666.1; ENSP00000533725.1; ENSG00000133961.23. [P49757-8] DR Ensembl; ENST00000863667.1; ENSP00000533726.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863668.1; ENSP00000533727.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863669.1; ENSP00000533728.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863670.1; ENSP00000533729.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000863671.1; ENSP00000533730.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000863672.1; ENSP00000533731.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000925288.1; ENSP00000595347.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000925290.1; ENSP00000595349.1; ENSG00000133961.23. [P49757-1] DR Ensembl; ENST00000925291.1; ENSP00000595350.1; ENSG00000133961.23. [P49757-7] DR Ensembl; ENST00000925293.1; ENSP00000595352.1; ENSG00000133961.23. [P49757-1] DR Ensembl; ENST00000925294.1; ENSP00000595353.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000957445.1; ENSP00000627504.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000957446.1; ENSP00000627505.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000957447.1; ENSP00000627506.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000957448.1; ENSP00000627507.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000957449.1; ENSP00000627508.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000957452.1; ENSP00000627511.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000957455.1; ENSP00000627514.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000957456.1; ENSP00000627515.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000957457.1; ENSP00000627516.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000957458.1; ENSP00000627517.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000957459.1; ENSP00000627518.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000957461.1; ENSP00000627520.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000957462.1; ENSP00000627521.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000957465.1; ENSP00000627524.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000957466.1; ENSP00000627525.1; ENSG00000133961.23. [P49757-6] DR Ensembl; ENST00000957467.1; ENSP00000627526.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000957468.1; ENSP00000627527.1; ENSG00000133961.23. [P49757-4] DR Ensembl; ENST00000957470.1; ENSP00000627529.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000957471.1; ENSP00000627530.1; ENSG00000133961.23. [P49757-3] DR Ensembl; ENST00000957472.1; ENSP00000627531.1; ENSG00000133961.23. [P49757-6] DR Ensembl; ENST00000957473.1; ENSP00000627532.1; ENSG00000133961.23. [P49757-2] DR Ensembl; ENST00000957474.1; ENSP00000627533.1; ENSG00000133961.23. [P49757-7] DR Ensembl; ENST00000957475.1; ENSP00000627534.1; ENSG00000133961.23. [P49757-2] 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 AGR; HGNC:8060; -. DR ClinPGx; PA31845; -. DR CTD; 8650; -. DR DisGeNET; 8650; -. DR GeneCards; NUMB; -. DR HGNC; HGNC:8060; NUMB. DR HPA; ENSG00000133961; Low tissue specificity. DR MalaCards; NUMB; -. DR MIM; 603728; gene. DR OpenTargets; ENSG00000133961; -. DR VEuPathDB; HostDB:ENSG00000133961; -. DR eggNOG; KOG3537; Eukaryota. DR GeneTree; ENSGT00940000156005; -. DR HOGENOM; CLU_031797_1_1_1; -. DR InParanoid; P49757; -. DR OMA; GMSYPAP; -. DR OrthoDB; 10070446at2759; -. DR PAN-GO; P49757; 4 GO annotations based on evolutionary models. DR PhylomeDB; P49757; -. 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 Reactome; R-HSA-9725554; Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin. DR SignaLink; P49757; -. DR SIGNOR; P49757; -. DR Agora; ENSG00000133961; -. DR BioGRID-ORCS; 8650; 17 hits in 1155 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 199 other cell types or tissues. DR ExpressionAtlas; P49757; baseline and differential. DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl. DR GO; GO:0016323; C:basolateral plasma membrane; IBA:GO_Central. 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:0031410; C:cytoplasmic vesicle; IBA:GO_Central. DR GO; GO:0005769; C:early endosome; IEA:Ensembl. DR GO; GO:0010008; C:endosome membrane; EXP:UniProtKB. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. 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: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:0030100; P:regulation of endocytosis; IMP:MGI. DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IEA:Ensembl. DR CDD; cd01268; PTB_Numb; 1. DR DisProt; DP01130; -. DR FunFam; 2.30.29.30:FF:000031; protein numb isoform X1; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 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; NUMB; 1. DR PANTHER; PTHR47368:SF5; PROTEIN NUMB HOMOLOG; 1. DR Pfam; PF06311; NumbF; 1. DR Pfam; PF00640; PID; 1. DR PIRSF; PIRSF017607; Numb/numb-like; 1. DR SMART; SM00462; PTB; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR PROSITE; PS01179; PID; 1. DR PDBsum; 5NJJ; -. DR PDBsum; 5NJK; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Developmental protein; KW Endosome; Membrane; Neurogenesis; Phosphoprotein; KW Proteomics identification; Reference proteome; 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..255 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 235..252 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 436..449 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 453..466 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 630..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 //