Recombinant Human Tripartite motif-containing protein 5 (TRIM5) Protein

Function

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)

Subcellular Location

Cytoplasm; Nucleus

Subunit

Can form homodimers and homotrimers. In addition to lower-order dimerization, also exhibits a higher-order multimerization and both low- and high-order multimerizations are essential for its restriction activity. Isoform Delta interacts with BTBD1 and BTBD2. Interacts with PSMC4, PSMC5, PSMD7 and HSPA8/HSC70 (By similarity). Interacts (via B30.2/SPRY domain) with HSPA1A/B. Interacts with PSMC2, MAP3K7/TAK1, TAB2 and TAB3 (PubMed:21512573, PubMed:22078707). Interacts with SQSTM1 (PubMed:20357094, PubMed:25127057). Interacts with TRIM6 and TRIM34 (PubMed:17156811, PubMed:21680743). Interacts with ULK1 (phosphorylated form), GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3C and BECN1 (PubMed:25127057)

Pathway

Protein modification; protein ubiquitination

• Reymond A. et al. The tripartite motif family identifies cell compartments. — EMBO J. (2001)
• Yap M.W. et al. Trim5alpha protein restricts both HIV-1 and murine leukemia virus. — Proc. Natl. Acad. Sci. U.S.A. (2004)
• Sawyer S.L. et al. High-frequency persistence of an impaired allele of the retroviral defense gene TRIM5alpha in humans. — Curr. Biol. (2006)
• Yamauchi K. et al. Ubiquitination of E3 ubiquitin ligase TRIM5 alpha and its potential role. — FEBS J. (2008)
• Battivelli E. et al. Modulation of TRIM5alpha activity in human cells by alternatively spliced TRIM5 isoforms. — J. Virol. (2011)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Taylor T.D. et al. Human chromosome 11 DNA sequence and analysis including novel gene identification. — Nature (2006)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)