Q5D7J0 · TRIM5_COLGU
- ProteinTripartite motif-containing protein 5
- GeneTRIM5
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids495 (go to sequence)
- Protein existenceInferred from homology
- Annotation score5/5
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
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTripartite motif-containing protein 5
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Colobinae > Colobus
Accessions
- Primary accessionQ5D7J0
- Secondary accessions
Subcellular Location
UniProt Annotation
GO Annotation
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
- Cellular component
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000273456 | 2-495 | Tripartite motif-containing protein 5 | |||
Sequence: ASGILVNIKEEVTCPICLELLTEPLSLHCGHSFCQACITANHKKSMLYKEGERSCPVCRISYQPENIRPNRHVANIVEKLREVKLSPEEGQKVDHCARHGEKLLLFCQEDRKVICWLCERSQEHRGHHTFLMEEVAQEYHVKLQTALEMLRQKQQEAEKLEADIREEKASWKIQIDYDKTNVLADFEQLREILDWEESNELQNLEKEEEDILKSLTKSETEMVQQTQYMRELVSDLEHRLQGSVMELLQGVDGIIKRIEDMTLKKPKTFPKNQRRVFRAPDLKGMLDMFRELTDVRRYWVDVTLAPNNISHAVIAEDKRRVSSPNPQIMYRAQGTLFQSLKNFIYCTGVLGSQSITSGKHYWEVDVSKKSAWILGVCAGFQPDAMYNIEQNENYQPKYGYWVIGLQEGVKYSVFQDGSSHTPFAPFIVPLSVIICPDRVGVFVDYEACTVSFFNITNHGFLIYKFSQCSFSKPVFPYLNPRKCTVPMTLCSPSS | ||||||
Modified residue | 87 | Phosphoserine | ||||
Sequence: S |
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
- PTM
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Zinc finger | 15-60 | RING-type | ||||
Sequence: CPICLELLTEPLSLHCGHSFCQACITANHKKSMLYKEGERSCPVCR | ||||||
Zinc finger | 92-133 | B box-type | ||||
Sequence: QKVDHCARHGEKLLLFCQEDRKVICWLCERSQEHRGHHTFLM | ||||||
Coiled coil | 137-225 | |||||
Sequence: AQEYHVKLQTALEMLRQKQQEAEKLEADIREEKASWKIQIDYDKTNVLADFEQLREILDWEESNELQNLEKEEEDILKSLTKSETEMVQ | ||||||
Region | 187-200 | Required for interaction with GABARAP and for autophagy | ||||
Sequence: FEQLREILDWEESN | ||||||
Domain | 283-495 | B30.2/SPRY | ||||
Sequence: LKGMLDMFRELTDVRRYWVDVTLAPNNISHAVIAEDKRRVSSPNPQIMYRAQGTLFQSLKNFIYCTGVLGSQSITSGKHYWEVDVSKKSAWILGVCAGFQPDAMYNIEQNENYQPKYGYWVIGLQEGVKYSVFQDGSSHTPFAPFIVPLSVIICPDRVGVFVDYEACTVSFFNITNHGFLIYKFSQCSFSKPVFPYLNPRKCTVPMTLCSPSS |
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
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length495
- Mass (Da)57,212
- Last updated2005-03-29 v1
- Checksum929315C287827257
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 391-392 | in Ref. 2; AAW55817 | ||||
Sequence: QN → RD | ||||||
Sequence conflict | 408 | in Ref. 2; AAW55817 | ||||
Sequence: E → K |