Q5D7J0 · TRIM5_COLGU

Function

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. Plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2.

Catalytic activity

  • S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.
    EC:2.3.2.27 (UniProtKB | ENZYME | Rhea)

Pathway

Protein modification; protein ubiquitination.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site97Zn2+ (UniProtKB | ChEBI)
Binding site100Zn2+ (UniProtKB | ChEBI)
Binding site119Zn2+ (UniProtKB | ChEBI)
Binding site125Zn2+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytosol
Cellular Componentnucleoplasm
Cellular ComponentP-body
Molecular Functionpattern recognition receptor activity
Molecular Functionprotein homodimerization activity
Molecular Functionprotein kinase binding
Molecular Functionubiquitin protein ligase activity
Molecular Functionubiquitin-protein transferase activity
Molecular Functionzinc ion binding
Biological Processactivation of innate immune response
Biological Processautophagy
Biological Processdefense response to virus
Biological Processinnate immune response
Biological Processpositive regulation of autophagy
Biological Processpositive regulation of canonical NF-kappaB signal transduction
Biological Processpositive regulation of MAPK cascade
Biological Processpositive regulation of NF-kappaB transcription factor activity
Biological Processprotein K63-linked ubiquitination
Biological Processregulation of lipopolysaccharide-mediated signaling pathway
Biological Processregulation of protein localization
Biological Processregulation of viral entry into host cell

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Tripartite motif-containing protein 5
  • EC number
  • Alternative names
    • RING-type E3 ubiquitin transferase TRIM5
    • TRIM5alpha

Gene names

    • Name
      TRIM5

Organism names

Accessions

  • Primary accession
    Q5D7J0
  • Secondary accessions
    • Q50EX2

Subcellular Location

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

Keywords

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain.

TypeIDPosition(s)Description
Initiator methionine1Removed
Modified residue2N-acetylalanine
ChainPRO_00002734562-495Tripartite motif-containing protein 5
Modified residue87Phosphoserine

Post-translational modification

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 (By similarity).

Keywords

Interaction

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. Interacts with BTBD1 and BTBD2. Interacts with PSMC4, PSMC5, PSMD7 and HSPA8/HSC70. Interacts (via B30.2/SPRY domain) with HSPA1A/B. Interacts with PSMC2, MAP3K7/TAK1, TAB2 and TAB3. Interacts with SQSTM1. Interacts with TRIM6 and TRIM34. Interacts with ULK1 (phosphorylated form), GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3C and BECN1.

Structure

Family & Domains

Features

Showing features for zinc finger, coiled coil, region, domain.

TypeIDPosition(s)Description
Zinc finger15-60RING-type
Zinc finger92-133B box-type
Coiled coil137-225
Region187-200Required for interaction with GABARAP and for autophagy
Domain283-495B30.2/SPRY

Domain

The B box-type zinc finger domain and the coiled-coil domain contribute to the higher and low order multimerization respectively which is essential for restriction activity. The coiled coil domain is important for higher order multimerization by promoting the initial dimerization.
The B30.2/SPRY domain acts as a capsid recognition domain. Polymorphisms in this domain explain the observed species-specific differences among orthologs (By similarity).
The RING-type zinc finger domain confers E3 ubiquitin ligase activity and is essential for retrovirus restriction activity, autoubiquitination and higher-order multimerization.

Sequence similarities

Belongs to the TRIM/RBCC family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    495
  • Mass (Da)
    57,212
  • Last updated
    2005-03-29 v1
  • Checksum
    929315C287827257
MASGILVNIKEEVTCPICLELLTEPLSLHCGHSFCQACITANHKKSMLYKEGERSCPVCRISYQPENIRPNRHVANIVEKLREVKLSPEEGQKVDHCARHGEKLLLFCQEDRKVICWLCERSQEHRGHHTFLMEEVAQEYHVKLQTALEMLRQKQQEAEKLEADIREEKASWKIQIDYDKTNVLADFEQLREILDWEESNELQNLEKEEEDILKSLTKSETEMVQQTQYMRELVSDLEHRLQGSVMELLQGVDGIIKRIEDMTLKKPKTFPKNQRRVFRAPDLKGMLDMFRELTDVRRYWVDVTLAPNNISHAVIAEDKRRVSSPNPQIMYRAQGTLFQSLKNFIYCTGVLGSQSITSGKHYWEVDVSKKSAWILGVCAGFQPDAMYNIEQNENYQPKYGYWVIGLQEGVKYSVFQDGSSHTPFAPFIVPLSVIICPDRVGVFVDYEACTVSFFNITNHGFLIYKFSQCSFSKPVFPYLNPRKCTVPMTLCSPSS

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict391-392in Ref. 2; AAW55817
Sequence conflict408in Ref. 2; AAW55817

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY843507
EMBL· GenBank· DDBJ
AAV91978.1
EMBL· GenBank· DDBJ
Genomic DNA
AY710298
EMBL· GenBank· DDBJ
AAW55817.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp