TRIM5
TRIM5 (tripartite motif containing 5, also known as TRIM5alpha or RNF88) is a RING-type E3 ubiquitin ligase of the TRIM family. It acts as a capsid-specific restriction factor against non-host-adapted retroviruses and as a pattern recognition receptor for the retroviral capsid lattice. Browse Assay Genie's current range of TRIM5 research reagents below, or read on for the biology behind the target.
TRIM5 is a capsid-specific restriction factor that prevents infection by non-host-adapted retroviruses. It blocks viral replication early in the life cycle, after viral entry but before reverse transcription. Beyond direct restriction, TRIM5 works as a pattern recognition receptor: binding to the viral capsid triggers its E3 ubiquitin ligase activity. Together with the heterodimeric UBE2V1-UBE2N (UBC13-UEV1A) complex, it generates 'Lys-63'-linked polyubiquitin chains, which promote autophosphorylation of the MAP3K7/TAK1 complex (TAK1, TAB2 and TAB3). This leads to induction of NF-kappa-B and MAPK-responsive inflammatory genes and an innate immune response in the infected cell.
The TRIM5 gene encodes a member of the tripartite motif family, also described as the TRIM/RBCC family. The TRIM motif comprises three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, followed by a coiled-coil region. The protein forms homo-oligomers through the coiled-coil region and localises to cytoplasmic bodies. It appears to ubiquitinate itself to regulate its own subcellular localisation. UniProt records it in the cytoplasm and nucleus, and multiple alternatively spliced transcript variants encoding different isoforms have been described. HGNC places it among the RING finger E3 ubiquitin protein ligases.
The restricted viruses include N-tropic murine leukaemia virus (N-MLV), equine infectious anaemia virus (EIAV), simian immunodeficiency virus of macaques (SIVmac), feline immunodeficiency virus (FIV) and bovine immunodeficiency virus (BIV). TRIM5 also contributes to autophagy: it activates BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2, and acts as a selective autophagy receptor that recognises HIV-1 capsid protein p24 and targets it for autophagic destruction.
TRIM5 blocks infection by non-host-adapted retroviruses after entry but before reverse transcription, making it a central subject in studies of capsid recognition.
Capsid binding activates TRIM5 ligase activity, Lys-63 polyubiquitin chains and TAK1 activation, driving NF-kappa-B and MAPK-responsive gene expression.
TRIM5 activates BECN1 and acts as a selective autophagy receptor that targets HIV-1 capsid protein p24 for degradation.
As a RING-type E3 ligase working with UBE2V1-UBE2N, TRIM5 is a model for ubiquitination-dependent regulation and self-ubiquitination of localisation.
TRIM5 is a capsid-specific restriction factor that blocks non-host-adapted retroviruses after entry but before reverse transcription. It also senses the capsid lattice, using E3 ligase activity to build Lys-63 polyubiquitin chains that activate TAK1 and induce NF-kappa-B and MAPK-responsive genes.
TRIM5 is also called TRIM5alpha and RNF88, and its full name is tripartite motif containing 5 (previously tripartite motif-containing 5). The gene produces multiple alternatively spliced transcript variants that encode different isoforms, according to the NCBI Gene summary.
UniProt lists N-tropic murine leukaemia virus, equine infectious anaemia virus, simian immunodeficiency virus of macaques, feline immunodeficiency virus and bovine immunodeficiency virus. TRIM5 also targets HIV-1 capsid protein p24 for autophagic destruction. Mouse and rat orthologues are not specified in the data here; check the datasheet of any product for its validated reactivity.
Other TRIM family E3 ligases involved in innate immunity, antiviral defence and ubiquitin signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9C035; product specifications from Assay Genie datasheets.