TRIM5

Description

The TRIM5 (tripartite motif containing 5) is a protein-coding gene located on chromosome 11.

Tripartite motif-containing protein 5, also known as RING finger protein 88, is a protein that in humans is encoded by the TRIM5 gene. The alpha isoform of this protein, TRIM5α, is a retrovirus restriction factor, which mediates a species-specific early block to retrovirus infection. TRIM5α is composed of 493 amino acids which is found in the cells of most primates. TRIM5α is an intrinsic immune factor important in the innate immune defense against retroviruses, along with the APOBEC family of proteins, tetherin and TRIM22. TRIM5α belongs to the TRIM protein family (TRIM stands for TRIpartite Motif); this family was first identified by Reddy in 1992 as a set of proteins which contain a RING type zinc finger domain, a B-box zinc binding domain, followed by a coiled-coil region. TRIM5α bears the C-terminal PRY-SPRY or B30.2 domain in addition to the other domains. When a retrovirus enters the host cell cytosol, the retroviral capsid was previously believed to undergo uncoating, though this (the complete uncoating theory) is now doubted; rather the true picture is thought to be that capsid uncoating does indeed take place in the cytosol but that it is a process which takes place progressively as the capsid gets closer and closer to the nucleus, though the uncoating process usually, but not always, completes in the nucleus. Further, the viral genome in the capsid is reverse transcribed inside the viral capsid to enable the production of daughter virions. TRIM5α is present in the cytosol. It recognizes motifs within viral capsid proteins, which causes the TRIM5α to smother the (not yet uncoated) viral capsid in a tessilatory manner so as to form a repeating regular hexagonal net, two sides of each hexagon being made up of two spokes of a three-way hub and spoke trimer and consequently by means of that smothering to interfere with any viral capsid uncoating process, thereby (1) preventing transport of the viral genome into the host cell nucleus and (2) also preventing successful reverse transcription of viral RNA into a length of DNA to be spliced into the host genome to enable expression of viral proteins via a transcrption process.

TRIM5 is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses. It blocks viral replication early in the life cycle, after viral entry but before reverse transcription. TRIM5 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. These chains 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. TRIM5 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). It plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2 (PubMed:25127057). TRIM5 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).

TRIM5 is also known as RNF88, TRIM5alpha.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing