Ubiquitin protein ligase
From Proteopedia
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<StructureSection load='4ljo' size='340' side='right' caption='Human UPL HOIP (grey) complex with ubiquitin (green), imidazole and Zn+2 ion (grey) [[4ljo]]' scene='' > | <StructureSection load='4ljo' size='340' side='right' caption='Human UPL HOIP (grey) complex with ubiquitin (green), imidazole and Zn+2 ion (grey) [[4ljo]]' scene='' > | ||
== Function == | == Function == | ||
| - | '''Ubiquitin-protein ligase''' (UPL) ('''E3''') in combination with ubiquitin-conjugating enzyme (E2) causes the attachment of ubiquitin to lysine in a target protein<ref>PMID:16250895</ref>. '''UPL XIAP''' or '''X-linked Inhibitor of Apoptosis Protein''' stops apoptosis induced by viral infection or by overproduction of caspases. UPL XIAP binds caspase-3, -7 and -9<ref>PMID:17549347</ref>. | + | '''Ubiquitin-protein ligase''' (UPL) ('''E3''') in combination with ubiquitin-conjugating enzyme (E2) causes the attachment of ubiquitin to lysine in a target protein<ref>PMID:16250895</ref>. '''UPL XIAP''' or '''X-linked Inhibitor of Apoptosis Protein''' stops apoptosis induced by viral infection or by overproduction of caspases. UPL XIAP binds caspase-3, -7 and -9<ref>PMID:17549347</ref>. UPL XIAP is inhibited by Smac – a death signaling protein. |
== Disease == | == Disease == | ||
| - | XIAP mutations cause X-linked lymphoproliferative syndrome type 2<ref>PMID:24942515</ref>. Parkin UPL has a direct causal role in neurodegenerative disorders<ref>PMID:16908979</ref>. | + | XIAP mutations cause X-linked lymphoproliferative syndrome type 2<ref>PMID:24942515</ref>. Parkin UPL has a direct causal role in neurodegenerative disorders<ref>PMID:16908979</ref>. |
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| + | == Relevance == | ||
| + | Overexpression of UPL XIAP functions as tumor marker. | ||
== Structural highlights == | == Structural highlights == | ||
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* '''UBR''' – a ca. 70 amino acid long zinc finger-like domain;<br /> | * '''UBR''' – a ca. 70 amino acid long zinc finger-like domain;<br /> | ||
* '''CUE''' – a ubiquitin-binding domain.<br /> | * '''CUE''' – a ubiquitin-binding domain.<br /> | ||
| - | '''UPL XIAP''' consists of 3 BIR (baculoviral IAP repeat) domains, followed by UBA (ubiquitin-binding) domain and RING (C-terminal RING finger) domain. BIR2 inhibits caspase-3 and -7. BIR3 inhibits caspase-9. | + | '''UPL XIAP''' consists of 3 BIR (baculoviral IAP repeat) domains, followed by UBA (ubiquitin-binding) domain and RING (C-terminal RING finger) domain. BIR2 inhibits caspase-3 and -7. BIR3 inhibits caspase-9. |
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| + | UPL contains an thioester-forming cysteine which catalyzes the transfer of ubiquitin from E2 to a substrate lysine. The surface interacting residues of UPL and the acceptor ubiquitin are shown here<ref>PMID:24141947</ref>. | ||
For some details see<br /> | For some details see<br /> | ||
*[[TIR1 ubiquitin ligase]]<br /> | *[[TIR1 ubiquitin ligase]]<br /> | ||
Revision as of 10:52, 1 December 2016
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3D Structures of ubiquitin protein ligase
Updated on 01-December-2016
References
- ↑ Ardley HC, Robinson PA. E3 ubiquitin ligases. Essays Biochem. 2005;41:15-30. PMID:16250895 doi:http://dx.doi.org/10.1042/EB0410015
- ↑ Sakemi R, Yano H, Ogasawara S, Akiba J, Nakashima O, Fukahori S, Sata M, Kojiro M. X-linked inhibitor of apoptosis (XIAP) and XIAP-associated factor-1 expressions and their relationship to apoptosis in human hepatocellular carcinoma and non-cancerous liver tissues. Oncol Rep. 2007 Jul;18(1):65-70. PMID:17549347
- ↑ Aguilar C, Lenoir C, Lambert N, Begue B, Brousse N, Canioni D, Berrebi D, Roy M, Gerart S, Chapel H, Schwerd T, Siproudhis L, Schappi M, Al-Ahmari A, Mori M, Yamaide A, Galicier L, Neven B, Routes J, Uhlig HH, Koletzko S, Patel S, Kanegane H, Picard C, Fischer A, Bensussan NC, Ruemmele F, Hugot JP, Latour S. Characterization of Crohn disease in X-linked inhibitor of apoptosis-deficient male patients and female symptomatic carriers. J Allergy Clin Immunol. 2014 Nov;134(5):1131-41.e9. doi:, 10.1016/j.jaci.2014.04.031. Epub 2014 Jun 15. PMID:24942515 doi:http://dx.doi.org/10.1016/j.jaci.2014.04.031
- ↑ Ardley HC, Robinson PA. The role of ubiquitin-protein ligases in neurodegenerative disease. Neurodegener Dis. 2004;1(2-3):71-87. PMID:16908979 doi:http://dx.doi.org/10.1159/000080048
- ↑ Stieglitz B, Rana RR, Koliopoulos MG, Morris-Davies AC, Schaeffer V, Christodoulou E, Howell S, Brown NR, Dikic I, Rittinger K. Structural basis for ligase-specific conjugation of linear ubiquitin chains by HOIP. Nature. 2013 Oct 20. doi: 10.1038/nature12638. PMID:24141947 doi:http://dx.doi.org/10.1038/nature12638
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