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Gene Review

NUMB  -  numb homolog (Drosophila)

Homo sapiens

Synonyms: C14orf41, Protein S171, Protein numb homolog, S171, c14_5527, ...
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Disease relevance of NUMB


High impact information on NUMB

  • This resulted in severe damage to brain lateral ventricle integrity and identified roles for Numb/Numblike in regulating ependymal wall integrity and SVZ neuroblast survival [5].
  • We demonstrate that the Hedgehog transcription factor Gli1 is targeted by Numb for Itch-dependent ubiquitination, which suppresses Hedgehog signals, thus arresting growth and promoting cell differentiation [6].
  • CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth [7].
  • We found that Numb was associated with L1, a neuronal cell adhesion molecule that is endocytosed and recycled at the growth cone, where CRMP-2 and Numb were colocalized [7].
  • These results suggest that in addition to regulating microtubule assembly, CRMP-2 is involved in polarized Numb-mediated endocytosis of proteins such as L1 [7].

Biological context of NUMB


Anatomical context of NUMB

  • We found that Numb localizes to endocytic organelles and is cotrafficked with internalizing receptors [10].
  • These results highlight a role of Numb for dendritic spine development and synaptic functions with intersectin and EphB2 [11].
  • We showed that inhibition of Notch activity by either overexpressing Numb or by using a pharmacological gamma-secretase inhibitor (DAPT) enhanced differentiation of murine and human myoblasts [12].
  • In epithelial cells, mammalian Numb localizes to the basolateral membrane and is excluded from the apical domain, which accumulates aPKC [9].
  • In addition to the previously described association of the PTB domain with the plasma membrane, we show that the AP2-binding motifs facilitate the association of Numb with cortical membrane punctae and vesicles [13].

Associations of NUMB with chemical compounds


Physical interactions of NUMB

  • The Mdm2 oncoprotein interacts with the cell fate regulator Numb [15].
  • The function of Numb has been linked to its ability to bind and to biologically antagonize Notch, a membrane receptor that also specifies cell fate [10].

Regulatory relationships of NUMB

  • Knockdown of Numb suppressed the ephrin-B1-induced spine development and maturation [11].

Other interactions of NUMB

  • Human homologue of Numb (hNumb) was cloned as Mdm2-binding protein by yeast two-hybrid screening [1].
  • Here, we identify the RING-type E3 ubiquitin ligase LNX (ligand of Numb protein X) as an Np9-interacting partner [16].
  • Many intracellular proteins, such as Fe65, Jip-1, Shc, Numb and X11alpha, interact with AID and modulate its function by different mechanisms [17].
  • Junctional adhesion molecule 4, LNX1 and Numb form a tripartite complex in vitro and are partially colocalized in heterologous cells [8].


  1. Mammalian Numb is a target protein of Mdm2, ubiquitin ligase. Yogosawa, S., Miyauchi, Y., Honda, R., Tanaka, H., Yasuda, H. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  2. Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. Pece, S., Serresi, M., Santolini, E., Capra, M., Hulleman, E., Galimberti, V., Zurrida, S., Maisonneuve, P., Viale, G., Di Fiore, P.P. J. Cell Biol. (2004) [Pubmed]
  3. Aberrant activation of notch signaling in human breast cancer. Stylianou, S., Clarke, R.B., Brennan, K. Cancer Res. (2006) [Pubmed]
  4. Characterization of human LNX, a novel ligand of Numb protein X that is downregulated in human gliomas. Chen, J., Xu, J., Zhao, W., Hu, G., Cheng, H., Kang, Y., Xie, Y., Lu, Y. Int. J. Biochem. Cell Biol. (2005) [Pubmed]
  5. Postnatal deletion of numb/numblike reveals repair and remodeling capacity in the subventricular neurogenic niche. Kuo, C.T., Mirzadeh, Z., Soriano-Navarro, M., Rasin, M., Wang, D., Shen, J., Sestan, N., Garcia-Verdugo, J., Alvarez-Buylla, A., Jan, L.Y., Jan, Y.N. Cell (2006) [Pubmed]
  6. Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination. Marcotullio, L.D., Ferretti, E., Greco, A., De Smaele, E., Po, A., Sico, M.A., Alimandi, M., Giannini, G., Maroder, M., Screpanti, I., Gulino, A. Nat. Cell Biol. (2006) [Pubmed]
  7. CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth. Nishimura, T., Fukata, Y., Kato, K., Yamaguchi, T., Matsuura, Y., Kamiguchi, H., Kaibuchi, K. Nat. Cell Biol. (2003) [Pubmed]
  8. Ligand-of-Numb protein X is an endocytic scaffold for junctional adhesion molecule 4. Kansaku, A., Hirabayashi, S., Mori, H., Fujiwara, N., Kawata, A., Ikeda, M., Rokukawa, C., Kurihara, H., Hata, Y. Oncogene (2006) [Pubmed]
  9. aPKC-mediated phosphorylation regulates asymmetric membrane localization of the cell fate determinant Numb. Smith, C.A., Lau, K.M., Rahmani, Z., Dho, S.E., Brothers, G., She, Y.M., Berry, D.M., Bonneil, E., Thibault, P., Schweisguth, F., Le Borgne, R., McGlade, C.J. EMBO J. (2007) [Pubmed]
  10. Numb is an endocytic protein. Santolini, E., Puri, C., Salcini, A.E., Gagliani, M.C., Pelicci, P.G., Tacchetti, C., Di Fiore, P.P. J. Cell Biol. (2000) [Pubmed]
  11. Role of numb in dendritic spine development with a Cdc42 GEF intersectin and EphB2. Nishimura, T., Yamaguchi, T., Tokunaga, A., Hara, A., Hamaguchi, T., Kato, K., Iwamatsu, A., Okano, H., Kaibuchi, K. Mol. Biol. Cell (2006) [Pubmed]
  12. Inhibition of Notch signaling induces myotube hypertrophy by recruiting a subpopulation of reserve cells. Kitzmann, M., Bonnieu, A., Duret, C., Vernus, B., Barro, M., Laoudj-Chenivesse, D., Verdi, J.M., Carnac, G. J. Cell. Physiol. (2006) [Pubmed]
  13. Dynamic regulation of mammalian numb by G protein-coupled receptors and protein kinase C activation: Structural determinants of numb association with the cortical membrane. Dho, S.E., Trejo, J., Siderovski, D.P., McGlade, C.J. Mol. Biol. Cell (2006) [Pubmed]
  14. Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. Sinha-Hikim, I., Cornford, M., Gaytan, H., Lee, M.L., Bhasin, S. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  15. The Mdm2 oncoprotein interacts with the cell fate regulator Numb. Juven-Gershon, T., Shifman, O., Unger, T., Elkeles, A., Haupt, Y., Oren, M. Mol. Cell. Biol. (1998) [Pubmed]
  16. Np9 protein of human endogenous retrovirus K interacts with ligand of numb protein X. Armbruester, V., Sauter, M., Roemer, K., Best, B., Hahn, S., Nty, A., Schmid, A., Philipp, S., Mueller, A., Mueller-Lantzsch, N. J. Virol. (2004) [Pubmed]
  17. The intracellular localization of amyloid beta protein precursor (AbetaPP) intracellular domain associated protein-1 (AIDA-1) is regulated by AbetaPP and alternative splicing. Ghersi, E., Vito, P., Lopez, P., Abdallah, M., D'Adamio, L. J. Alzheimers Dis. (2004) [Pubmed]
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