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Gene Review

UNC5B  -  unc-5 homolog B (C. elegans)

Homo sapiens

Synonyms: Netrin receptor UNC5B, P53RDL1, Protein unc-5 homolog 2, Protein unc-5 homolog B, UNC5H2, ...
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Disease relevance of UNC5B


High impact information on UNC5B

  • The p53RDL1 gene product contains a cytoplasmic carboxy-terminal death domain that is highly homologous to rat Unc5H2, a dependence receptor involved in the regulation of apoptosis, as well as in axon guidance and migration of neural cells [2].
  • Conversely, when p53RDL1 interacted with its ligand, Netrin-1, p53-dependent apoptosis was blocked [2].
  • Here, we show that UNC5H2 physically interacts with the serine/threonine kinase death-associated protein kinase (DAP-kinase) both in cell culture and in embryonic mouse brains [3].
  • The lossreduction of expression may be a crucial mechanism for tumorigenicity because the expression of UNC5H1, UNC5H2, or UNC5H3 inhibits tumor cell anchorage-independent growth and invasion [1].
  • The antimelanoma effect of IFN-gamma was also associated with the up-regulation of the proapoptotic dependence receptor UNC5H2 and the Wnt inhibitor Dkk-1 [4].

Biological context of UNC5B


Associations of UNC5B with chemical compounds

  • In particular, Semaphorin3E and its receptor plexinD1 in addition to the Netrin receptor UNC5B have recently been shown to direct endothelial tip cell navigation [7].

Regulatory relationships of UNC5B

  • UNC5H2-induced apoptosis depends on the interaction of the death domain at the C-terminus with the DAP-kinase death domain and caspase cleavage near the transmembrane region [8].


  1. The netrin-1 receptors UNC5H are putative tumor suppressors controlling cell death commitment. Thiebault, K., Mazelin, L., Pays, L., Llambi, F., Joly, M.O., Scoazec, J.Y., Saurin, J.C., Romeo, G., Mehlen, P. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  2. p53RDL1 regulates p53-dependent apoptosis. Tanikawa, C., Matsuda, K., Fukuda, S., Nakamura, Y., Arakawa, H. Nat. Cell Biol. (2003) [Pubmed]
  3. The dependence receptor UNC5H2 mediates apoptosis through DAP-kinase. Llambi, F., Lourenço, F.C., Gozuacik, D., Guix, C., Pays, L., Del Rio, G., Kimchi, A., Mehlen, P. EMBO J. (2005) [Pubmed]
  4. Gene expression changes and signaling events associated with the direct antimelanoma effect of IFN-gamma. Gollob, J.A., Sciambi, C.J., Huang, Z., Dressman, H.K. Cancer Res. (2005) [Pubmed]
  5. p53, apoptosis and axon-guidance molecules. Arakawa, H. Cell Death Differ. (2005) [Pubmed]
  6. Modulation of G(ialpha(2)) signaling by the axonal guidance molecule UNC5H2. Komatsuzaki, K., Dalvin, S., Kinane, T.B. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  7. Guidance of vascular and neural network formation. Eichmann, A., Le Noble, F., Autiero, M., Carmeliet, P. Curr. Opin. Neurobiol. (2005) [Pubmed]
  8. Structure of the UNC5H2 death domain. Handa, N., Kukimoto-Niino, M., Akasaka, R., Murayama, K., Terada, T., Inoue, M., Yabuki, T., Aoki, M., Seki, E., Matsuda, T., Nunokawa, E., Tanaka, A., Hayashizaki, Y., Kigawa, T., Shirouzu, M., Yokoyama, S. Acta Crystallogr. D Biol. Crystallogr. (2006) [Pubmed]
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