9le4

Structural highlights

Disease

STABP_HUMAN Microcephaly-capillary malformation syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

STABP_HUMAN Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not cleave 'Lys-48'-linked polyubiquitin chains (By similarity). Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF. Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7. Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes. Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization (By similarity). Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways.^{[1] [2] [3] [4] [5]}

References

1. ↑ Tanaka N, Kaneko K, Asao H, Kasai H, Endo Y, Fujita T, Takeshita T, Sugamura K. Possible involvement of a novel STAM-associated molecule "AMSH" in intracellular signal transduction mediated by cytokines. J Biol Chem. 1999 Jul 2;274(27):19129-35. PMID:10383417
2. ↑ Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S. Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads. EMBO J. 2001 Aug 1;20(15):4132-42. PMID:11483516 doi:http://dx.doi.org/10.1093/emboj/20.15.4132
3. ↑ McCullough J, Clague MJ, Urbe S. AMSH is an endosome-associated ubiquitin isopeptidase. J Cell Biol. 2004 Aug 16;166(4):487-92. PMID:15314065 doi:http://dx.doi.org/10.1083/jcb.200401141
4. ↑ Ma YM, Boucrot E, Villen J, Affar el B, Gygi SP, Gottlinger HG, Kirchhausen T. Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation. J Biol Chem. 2007 Mar 30;282(13):9805-12. Epub 2007 Jan 29. PMID:17261583 doi:http://dx.doi.org/10.1074/jbc.M611635200
5. ↑ McDonell LM, Mirzaa GM, Alcantara D, Schwartzentruber J, Carter MT, Lee LJ, Clericuzio CL, Graham JM Jr, Morris-Rosendahl DJ, Polster T, Acsadi G, Townshend S, Williams S, Halbert A, Isidor B, David A, Smyser CD, Paciorkowski AR, Willing M, Woulfe J, Das S, Beaulieu CL, Marcadier J, Geraghty MT, Frey BJ, Majewski J, Bulman DE, Dobyns WB, O'Driscoll M, Boycott KM. Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome. Nat Genet. 2013 May;45(5):556-62. doi: 10.1038/ng.2602. Epub 2013 Mar 31. PMID:23542699 doi:http://dx.doi.org/10.1038/ng.2602