Background: | 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). Plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. 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. |
Synonyms: | Tripartite motif-containing protein 5 (EC 2.3.2.27) (RING finger protein 88) (RING-type E3 ubiquitin transferase TRIM5), TRIM5, RNF88 |
UniProt Protein Function: | TRIM5: Isoform Alpha is a retrovirus restriction factor, which mediates species-specific, early block to retrovirus infection. Targets retroviral capsid soon after entry into the cell, and prevents reverse transcription of the virus RNA genome. Isoform Alpha trimers may make multiple contacts with the hexameric lattice of CA proteins which constitute the surface of retrovirion core, and somehow inactivate the virus. Restricts efficiently infection by N-MLV, but not HIV-1. May have E3 ubiquitin-protein ligase activity. Belongs to the TRIM/RBCC family. 6 isoforms of the human protein are produced by alternative splicing. |
UniProt Protein Details: | Protein type:EC 6.3.2.19; EC 6.3.2.-; Ubiquitin conjugating system; Ligase; Ubiquitin ligase Chromosomal Location of Human Ortholog: 11p15 Cellular Component: cytoplasm; cytosol Molecular Function:identical protein binding; protein binding; protein homodimerization activity; zinc ion binding; ubiquitin-protein ligase activity; pattern recognition receptor activity; ligase activity Biological Process: positive regulation of I-kappaB kinase/NF-kappaB cascade; viral reproduction; positive regulation of MAPKKK cascade; negative regulation of virion penetration into host cell; cytokine and chemokine mediated signaling pathway; innate immune response; positive regulation of transcription factor activity; pattern recognition receptor signaling pathway; activation of innate immune response; regulation of lipopolysaccharide-mediated signaling pathway; defense response to virus; activation of NF-kappaB transcription factor |
NCBI Summary: | 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] |
UniProt Code: | Q9C035 |
NCBI GenInfo Identifier: | 283046694 |
NCBI Gene ID: | 85363 |
NCBI Accession: | NP_149023.2 |
UniProt Secondary Accession: | Q9C035,Q2MLV4, Q2MLV8, Q2MLV9, Q2MLW1, Q2MLW3, Q2MLW4 A6NGQ1, A8WFA8, D3DQS8, D3DQS9, G3GJY1, |
UniProt Related Accession: | Q9C035 |
Molecular Weight: | 70.3 kDa |
NCBI Full Name: | tripartite motif-containing protein 5 isoform alpha |
NCBI Synonym Full Names: | tripartite motif containing 5 |
NCBI Official Symbol: | TRIM5 |
NCBI Official Synonym Symbols: | RNF88; TRIM5alpha |
NCBI Protein Information: | tripartite motif-containing protein 5; ring finger protein 88; tripartite motif protein TRIM5; tripartite motif containing 5 transcript variant iota; tripartite motif containing 5 transcript variant kappa |
UniProt Protein Name: | Tripartite motif-containing protein 5 |
UniProt Synonym Protein Names: | RING finger protein 88 |
Protein Family: | Tripartite motif-containing protein |
UniProt Gene Name: | TRIM5 |
UniProt Entry Name: | TRIM5_HUMAN |