| 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] [CHMP3_HUMAN] Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Selectively binds to phosphatidylinositol 3,5-bisphosphate PtdIns(3,5)P2 and PtdIns(3,4)P2 in preference to other phosphoinositides tested. Involved in late stages of cytokinesis. Plays a role in endosomal sorting/trafficking of EGF receptor. Isoform 2 prevents stress-mediated cell death and accumulation of reactive oxygen species when expressed in yeast cells.[6] [7] [8] [9] [10]
Publication Abstract from PubMed
Endosomal sorting complexes required for transport (ESCRT) recognize ubiquitinated cargo and catalyze diverse budding processes including multivesicular body biogenesis, enveloped virus egress, and cytokinesis. We present the crystal structure of an N-terminal fragment of the deubiquitinating enzyme AMSH (AMSHDeltaC) in complex with the C-terminal region of ESCRT-III CHMP3 (CHMP3DeltaN). AMSHDeltaC folds into an elongated 90 A long helical assembly that includes an unusual MIT domain. CHMP3DeltaN is unstructured in solution and helical in complex with AMSHDeltaC, revealing a novel MIT domain interacting motif (MIM) that does not overlap with the CHMP1-AMSH binding site. ITC and SPR measurements demonstrate an unusual high-affinity MIM-MIT interaction. Structural analysis suggests a regulatory role for the N-terminal helical segment of AMSHDeltaC and its destabilization leads to a loss of function during HIV-1 budding. Our results indicate a tight coupling of ESCRT-III CHMP3 and AMSH functions and provide insight into the regulation of ESCRT-III.
Structural Basis for ESCRT-III CHMP3 Recruitment of AMSH.,Solomons J, Sabin C, Poudevigne E, Usami Y, Hulsik DL, Macheboeuf P, Hartlieb B, Gottlinger H, Weissenhorn W Structure. 2011 Aug 10;19(8):1149-59. PMID:21827950[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Yan Q, Hunt PR, Frelin L, Vida TA, Pevsner J, Bean AJ. mVps24p functions in EGF receptor sorting/trafficking from the early endosome. Exp Cell Res. 2005 Mar 10;304(1):265-73. Epub 2004 Dec 1. PMID:15707591 doi:10.1016/j.yexcr.2004.11.003
- ↑ Khoury CM, Yang Z, Ismail S, Greenwood MT. Characterization of a novel alternatively spliced human transcript encoding an N-terminally truncated Vps24 protein that suppresses the effects of Bax in an ESCRT independent manner in yeast. Gene. 2007 Apr 15;391(1-2):233-41. Epub 2007 Jan 26. PMID:17331679 doi:10.1016/j.gene.2006.12.039
- ↑ von Schwedler UK, Stuchell M, Muller B, Ward DM, Chung HY, Morita E, Wang HE, Davis T, He GP, Cimbora DM, Scott A, Krausslich HG, Kaplan J, Morham SG, Sundquist WI. The protein network of HIV budding. Cell. 2003 Sep 19;114(6):701-13. PMID:14505570
- ↑ Dukes JD, Richardson JD, Simmons R, Whitley P. A dominant-negative ESCRT-III protein perturbs cytokinesis and trafficking to lysosomes. Biochem J. 2008 Apr 15;411(2):233-9. PMID:18076377 doi:10.1042/BJ20071296
- ↑ Muziol T, Pineda-Molina E, Ravelli RB, Zamborlini A, Usami Y, Gottlinger H, Weissenhorn W. Structural basis for budding by the ESCRT-III factor CHMP3. Dev Cell. 2006 Jun;10(6):821-30. PMID:16740483 doi:10.1016/j.devcel.2006.03.013
- ↑ Solomons J, Sabin C, Poudevigne E, Usami Y, Hulsik DL, Macheboeuf P, Hartlieb B, Gottlinger H, Weissenhorn W. Structural Basis for ESCRT-III CHMP3 Recruitment of AMSH. Structure. 2011 Aug 10;19(8):1149-59. PMID:21827950 doi:10.1016/j.str.2011.05.011
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