TRIM5

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

TRIM5 Gene(Protein Coding) Tripartite Motif Containing 5

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), equine infectious anemia virus (EIAV), simian immunodeficiency virus of macaques (SIVmac), feline immunodeficiency virus (FIV), and bovine immunodeficiency virus (BIV) (PubMed:17156811).
Plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2 (PubMed:25127057).
Also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction (PubMed:25127057).

Biological Process activation of innate immune response Source:UniProtKB1 Publication
Biological Process autophagy Source:UniProtKB1 Publication
Biological Process defense response to virus Source:UniProtKB2 Publications
Biological Process innate immune response Source:UniProtKB1 Publication
Biological Process negative regulation of viral entry into host cell Source:UniProtKB1 Publication
Biological Process positive regulation of autophagy Source:GO_Central1 Publication
Biological Process positive regulation of DNA-binding transcription factor activity Source:UniProtKB1 Publication
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signaling Source:UniProtKB1 Publication
Biological Process positive regulation of MAPK cascade Source:UniProtKB1 Publication
Biological Process positive regulation of NF-kappaB transcription factor activity Source:UniProtKB2 Publications
Biological Process protein K63-linked ubiquitination Source:UniProtKB1 Publication
Biological Process protein polyubiquitination Source:GO_Central1 Publication
Biological Process protein ubiquitination Source:GO_Central1 Publication
Biological Process regulation of gene expression Source:GO_Central1 Publication
Biological Process regulation of lipopolysaccharide-mediated signaling pathway Source:UniProtKB1 Publication
Biological Process regulation of protein localization Source:UniProtKB1 Publication
Biological Process regulation of viral entry into host cell Source:GO_Central1 Publication
Biological Process suppression of viral release by host Source:UniProtKB1 Publication

Cytoplasm
Nucleus
Predominantly localizes in cytoplasmic bodies (PubMed:12878161, PubMed:20357094).
Localization may be influenced by the coexpression of other TRIM proteins, hence partial nuclear localization is observed in the presence of TRIM22 or TRIM27 (By similarity).
In cytoplasmic bodies, colocalizes with proteasomal subunits and SQSTM1 (By similarity).

Degraded in a proteasome-independent fashion in the absence of viral infection but in a proteasome-dependent fashion following exposure to restriction sensitive virus.
Autoubiquitinated in a RING finger- and UBE2D2-dependent manner. Monoubiquitinated by TRIM21. Deubiquitinated by Yersinia YopJ. Ubiquitination may not lead to proteasomal degradation.