Ubiquitin protein ligase

From Proteopedia

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Revision as of 08:32, 4 December 2016

Human UPL HOIP (magenta) complex with ubiquitin (green), imidazole and Zn+2 ion (grey) 4ljo

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1 Function
2 Disease
3 Relevance
4 Structural highlights

Function

Ubiquitin-protein ligase (UPL) (E3) in combination with ubiquitin-conjugating enzyme (E2) causes the attachment of ubiquitin to lysine in a target protein^[1]. 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^[2]. UPL XIAP is inhibited by Smac – a death signaling protein.

Disease

XIAP mutations cause X-linked lymphoproliferative syndrome type 2^[3]. Parkin UPL has a direct causal role in neurodegenerative disorders^[4].

Relevance

Overexpression of UPL XIAP functions as tumor marker.

Structural highlights

UPL can contain several distinct domains like:

WW domains which contain 2 tryptophans which bind proline-rich peptide;
UBA – Ubiquitin-Associated Domain;
TKB – Tyrosine Kinase Binding domain;
C2 – an 8 β strand domain which coordinates targeting proteins toward cell membrane;
HECT – Homologous to the E6-AP C-terminus;
RING – Really Intersting New Gene involved in binding to E2;
FHA – Forkhead Associated domain recognizing phosphothreonine;
IBR – involved in binding to E2;
PHD finger – Plant Homeo Domain is 50-80 amino acid long which contains a CHC motif;
SRA – SET and RING-Associated domain;
TUDOR – a ca. 50 amino acids long and recognizes dimethylated arginine;
CPH – protein-protein interaction domain;
UBR – a ca. 70 amino acid long zinc finger-like domain;
CUE – a ubiquitin-binding domain.

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 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^[5].

For some details see

3D Structures of ubiquitin protein ligase

Updated on 04-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

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Tihitina Y Aytenfisu, Joel L. Sussman

Retrieved from "http://52.214.119.220/wiki/index.php/Ubiquitin_protein_ligase"

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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>.
+<scene name='53/537519/Cv/2'>Ubiquitin/protein ligase interface shown in space-filled representation</scene>.
 For some details see<br />
 *[[TIR1 ubiquitin ligase]]<br />

Ubiquitin protein ligase

From Proteopedia

Revision as of 08:32, 4 December 2016

Contents

Function

Disease

Relevance

Structural highlights

3D Structures of ubiquitin protein ligase

References

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