NUMB (gene)

Numb homolog (Drosophila)
PDB rendering based on 1wj1.
Available structures PDB 1wj1
Identifiers
Symbols	NUMB; S171
External IDs	OMIM: 603728 MGI: 107423 HomoloGene: 2775 GeneCards: NUMB Gene
Gene Ontology Molecular function • protein binding • beta-catenin binding • alpha-catenin binding • cadherin binding Cellular component • nucleus • cytoplasm • early endosome • plasma membrane • integral to plasma membrane • basolateral plasma membrane • extrinsic to plasma membrane • apical part of cell Biological process • multicellular organismal development • nervous system development • neuroblast proliferation • axon guidance • lateral ventricle development • neuroblast division in subventricular zone • forebrain development • adherens junction organization • positive regulation of neurogenesis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8650	18222
Ensembl	ENSG00000133961	ENSMUSG00000021224
UniProt	P49757	Q05BE7
RefSeq (mRNA)	NM_001005743.1	NM_010949
RefSeq (protein)	NP_001005743.1	NP_035079
Location (UCSC)	Chr 14: 73.74 – 73.93 Mb	Chr 12: 85.13 – 85.26 Mb
PubMed search	[1]	[2]

Protein numb homolog is a protein that in humans is encoded by the NUMB gene.

The protein encoded by this gene plays a role in the determination of cell fates during development. The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1. Four transcript variants encoding different isoforms have been found for this gene.^[1]

Interactions

NUMB (gene) has been shown to interact with Adaptor-related protein complex 2, alpha 1,^[2] Mdm2,^[3][4] L1,^[2] DPYSL2,^[2] SIAH1,^[5] P53^[4] and LNX1.^[6]

References

1. ^ "Entrez Gene: NUMB numb homolog (Drosophila)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8650. 
2. ^ ^{a b c} Nishimura, Takashi; Fukata Yuko, Kato Katsuhiro, Yamaguchi Tomoya, Matsuura Yoshiharu, Kamiguchi Hiroyuki, Kaibuchi Kozo (September 2003). "CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth". Nat. Cell Biol. (England) 5 (9): 819–26. doi:10.1038/ncb1039. ISSN 1465-7392. PMID 12942088. 
3. ^ Yogosawa, Satomi; Miyauchi Yasuhiro, Honda Reiko, Tanaka Hirofumi, Yasuda Hideyo (March 2003). "Mammalian Numb is a target protein of Mdm2, ubiquitin ligase". Biochem. Biophys. Res. Commun. (United States) 302 (4): 869–72. doi:10.1016/S0006-291X(03)00282-1. ISSN 0006-291X. PMID 12646252. 
4. ^ ^{a b} Colaluca, Ivan N; Tosoni Daniela, Nuciforo Paolo, Senic-Matuglia Francesca, Galimberti Viviana, Viale Giuseppe, Pece Salvatore, Di Fiore Pier Paolo (January 2008). "NUMB controls p53 tumour suppressor activity". Nature (England) 451 (7174): 76–80. doi:10.1038/nature06412. PMID 18172499. 
5. ^ Susini, L; Passer B J, Amzallag-Elbaz N, Juven-Gershon T, Prieur S, Privat N, Tuynder M, Gendron M C, Israël A, Amson R, Oren M, Telerman A (December 2001). "Siah-1 binds and regulates the function of Numb". Proc. Natl. Acad. Sci. U.S.A. (United States) 98 (26): 15067–72. doi:10.1073/pnas.261571998. ISSN 0027-8424. PMC 64984. PMID 11752454. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=64984. 
6. ^ Nie, Jing; McGill Melanie A, Dermer Matt, Dho Sascha E, Wolting Cheryl D, McGlade C Jane (January 2002). "LNX functions as a RING type E3 ubiquitin ligase that targets the cell fate determinant Numb for ubiquitin-dependent degradation". EMBO J. (England) 21 (1–2): 93–102. doi:10.1093/emboj/21.1.93. ISSN 0261-4189. PMC 125803. PMID 11782429. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125803. 

Further reading

• Wong WT, Schumacher C, Salcini AE, et al. (1995). "A protein-binding domain, EH, identified in the receptor tyrosine kinase substrate Eps15 and conserved in evolution". Proc. Natl. Acad. Sci. U.S.A. 92 (21): 9530–4. doi:10.1073/pnas.92.21.9530. PMC 40835. PMID 7568168. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=40835. 
• Sherrington R, Rogaev EI, Liang Y, et al. (1995). "Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease". Nature 375 (6534): 754–60. doi:10.1038/375754a0. PMID 7596406. 
• Zhong W, Feder JN, Jiang MM, et al. (1996). "Asymmetric localization of a mammalian numb homolog during mouse cortical neurogenesis". Neuron 17 (1): 43–53. doi:10.1016/S0896-6273(00)80279-2. PMID 8755477. 
• Salcini AE, Confalonieri S, Doria M, et al. (1997). "Binding specificity and in vivo targets of the EH domain, a novel protein–protein interaction module". Genes Dev. 11 (17): 2239–49. doi:10.1101/gad.11.17.2239. PMC 275390. PMID 9303539. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=275390. 
• Dho SE, Jacob S, Wolting CD, et al. (1998). "The mammalian numb phosphotyrosine-binding domain. Characterization of binding specificity and identification of a novel PDZ domain-containing numb binding protein, LNX". J. Biol. Chem. 273 (15): 9179–87. doi:10.1074/jbc.273.15.9179. PMID 9535908. 
• Juven-Gershon T, Shifman O, Unger T, et al. (1998). "The Mdm2 Oncoprotein Interacts with the Cell Fate Regulator Numb". Mol. Cell. Biol. 18 (7): 3974–82. PMC 108982. PMID 9632782. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=108982. 
• Verdi JM, Bashirullah A, Goldhawk DE, et al. (1999). "Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage". Proc. Natl. Acad. Sci. U.S.A. 96 (18): 10472–6. doi:10.1073/pnas.96.18.10472. PMC 17913. PMID 10468633. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=17913. 
• Santolini E, Puri C, Salcini AE, et al. (2001). "Numb Is an Endocytic Protein". J. Cell Biol. 151 (6): 1345–52. doi:10.1083/jcb.151.6.1345. PMC 2190585. PMID 11121447. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2190585. 
• Susini L, Passer BJ, Amzallag-Elbaz N, et al. (2002). "Siah-1 binds and regulates the function of Numb". Proc. Natl. Acad. Sci. U.S.A. 98 (26): 15067–72. doi:10.1073/pnas.261571998. PMC 64984. PMID 11752454. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=64984. 
• Nie J, McGill MA, Dermer M, et al. (2002). "LNX functions as a RING type E3 ubiquitin ligase that targets the cell fate determinant Numb for ubiquitin-dependent degradation". EMBO J. 21 (1–2): 93–102. doi:10.1093/emboj/21.1.93. PMC 125803. PMID 11782429. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125803. 
• Rice DS, Northcutt GM, Kurschner C (2002). "The Lnx family proteins function as molecular scaffolds for Numb family proteins". Mol. Cell. Neurosci. 18 (5): 525–40. doi:10.1006/mcne.2001.1024. PMID 11922143. 
• Roncarati R, Sestan N, Scheinfeld MH, et al. (2002). "The γ-secretase-generated intracellular domain of β-amyloid precursor protein binds Numb and inhibits Notch signaling". Proc. Natl. Acad. Sci. U.S.A. 99 (10): 7102–7. doi:10.1073/pnas.102192599. PMC 124535. PMID 12011466. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=124535. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Calderwood DA, Fujioka Y, de Pereda JM, et al. (2003). "Integrin β cytoplasmic domain interactions with phosphotyrosine-binding domains: A structural prototype for diversity in integrin signaling". Proc. Natl. Acad. Sci. U.S.A. 100 (5): 2272–7. doi:10.1073/pnas.262791999. PMC 151330. PMID 12606711. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=151330. 
• Yogosawa S, Miyauchi Y, Honda R, et al. (2003). "Mammalian Numb is a target protein of Mdm2, ubiquitin ligase". Biochem. Biophys. Res. Commun. 302 (4): 869–72. doi:10.1016/S0006-291X(03)00282-1. PMID 12646252. 
• McGill MA, McGlade CJ (2003). "Mammalian numb proteins promote Notch1 receptor ubiquitination and degradation of the Notch1 intracellular domain". J. Biol. Chem. 278 (25): 23196–203. doi:10.1074/jbc.M302827200. PMID 12682059. 
• Rossé C, L'Hoste S, Offner N, et al. (2003). "RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to phosphorylate epsin during the switch off of endocytosis in mitosis". J. Biol. Chem. 278 (33): 30597–604. doi:10.1074/jbc.M302191200. PMID 12775724. 
• Nishimura T, Fukata Y, Kato K, et al. (2003). "CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth". Nat. Cell Biol. 5 (9): 819–26. doi:10.1038/ncb1039. PMID 12942088. 
• Qin H, Percival-Smith A, Li C, et al. (2004). "A novel transmembrane protein recruits numb to the plasma membrane during asymmetric cell division". J. Biol. Chem. 279 (12): 11304–12. doi:10.1074/jbc.M311733200. PMID 14670962. 
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.