2yrg

Structural highlights

Function

TRIM5_HUMAN Capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses. Blocks viral replication early in the life cycle, after viral entry but before reverse transcription. In addition to acting as a capsid-specific restriction factor, also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Binding to the viral capsid triggers its E3 ubiquitin ligase activity, and in concert with the heterodimeric ubiquitin conjugating enzyme complex UBE2V1-UBE2N (also known as UBC13-UEV1A complex) generates 'Lys-63'-linked polyubiquitin chains, which in turn are catalysts in the autophosphorylation of the MAP3K7/TAK1 complex (includes TAK1, TAB2, and TAB3). Activation of the MAP3K7/TAK1 complex by autophosphorylation results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes, thereby leading to an innate immune response in the infected cell. Restricts infection by N-tropic murine leukemia virus (N-MLV) and equine infectious anemia virus (EIAV).^{[1] [2] [3] [4] [5] [6] [7] [8]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Yamauchi K, Wada K, Tanji K, Tanaka M, Kamitani T. Ubiquitination of E3 ubiquitin ligase TRIM5 alpha and its potential role. FEBS J. 2008 Apr;275(7):1540-55. doi: 10.1111/j.1742-4658.2008.06313.x. Epub 2008, Feb 25. PMID:18312418 doi:http://dx.doi.org/10.1111/j.1742-4658.2008.06313.x
2. ↑ Battivelli E, Migraine J, Lecossier D, Matsuoka S, Perez-Bercoff D, Saragosti S, Clavel F, Hance AJ. Modulation of TRIM5alpha activity in human cells by alternatively spliced TRIM5 isoforms. J Virol. 2011 Aug;85(15):7828-35. doi: 10.1128/JVI.00648-11. Epub 2011 Jun 1. PMID:21632761 doi:http://dx.doi.org/10.1128/JVI.00648-11
3. ↑ Xu L, Yang L, Moitra PK, Hashimoto K, Rallabhandi P, Kaul S, Meroni G, Jensen JP, Weissman AM, D'Arpa P. BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5delta. Exp Cell Res. 2003 Aug 1;288(1):84-93. PMID:12878161
4. ↑ Passerini LD, Keckesova Z, Towers GJ. Retroviral restriction factors Fv1 and TRIM5alpha act independently and can compete for incoming virus before reverse transcription. J Virol. 2006 Mar;80(5):2100-5. PMID:16474118 doi:http://dx.doi.org/10.1128/JVI.80.5.2100-2105.2006
5. ↑ Stremlau M, Song B, Javanbakht H, Perron M, Sodroski J. Cyclophilin A: an auxiliary but not necessary cofactor for TRIM5alpha restriction of HIV-1. Virology. 2006 Jul 20;351(1):112-20. Epub 2006 Apr 27. PMID:16643975 doi:http://dx.doi.org/10.1016/j.virol.2006.03.015
6. ↑ Pertel T, Hausmann S, Morger D, Zuger S, Guerra J, Lascano J, Reinhard C, Santoni FA, Uchil PD, Chatel L, Bisiaux A, Albert ML, Strambio-De-Castillia C, Mothes W, Pizzato M, Grutter MG, Luban J. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature. 2011 Apr 21;472(7343):361-5. doi: 10.1038/nature09976. PMID:21512573 doi:10.1038/nature09976
7. ↑ Tareen SU, Emerman M. Human Trim5alpha has additional activities that are uncoupled from retroviral capsid recognition. Virology. 2011 Jan 5;409(1):113-20. doi: 10.1016/j.virol.2010.09.018. Epub 2010, Oct 28. PMID:21035162 doi:10.1016/j.virol.2010.09.018
8. ↑ Nakayama EE, Shioda T. TRIM5alpha and Species Tropism of HIV/SIV. Front Microbiol. 2012;3:13. doi: 10.3389/fmicb.2012.00013. Epub 2012 Jan 24. PMID:22291694 doi:10.3389/fmicb.2012.00013