Q9C035 · TRIM5_HUMAN
- ProteinTripartite motif-containing protein 5
- GeneTRIM5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids493 (go to sequence)
- Protein existenceEvidence at protein level
- 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. 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).
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).
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
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameTripartite motif-containing protein 5
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9C035
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Predominantly localizes in cytoplasmic bodies (PubMed:12878161, PubMed:20357094).
Localization may be influenced by the coexpression of other TRIM proteins, hence partial nuclear localization is observed in the presence of TRIM22 or TRIM27 (By similarity).
In cytoplasmic bodies, colocalizes with proteasomal subunits and SQSTM1 (By similarity).
Localization may be influenced by the coexpression of other TRIM proteins, hence partial nuclear localization is observed in the presence of TRIM22 or TRIM27 (By similarity).
In cytoplasmic bodies, colocalizes with proteasomal subunits and SQSTM1 (By similarity).
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 15 | Abolishes E3 ligase activity. | ||||
Sequence: C → A | ||||||
Natural variant | VAR_060707 | 31 | in dbSNP:rs59896509 | |||
Sequence: G → S | ||||||
Natural variant | VAR_017397 | 43 | in dbSNP:rs3740996 | |||
Sequence: H → Y | ||||||
Natural variant | VAR_060708 | 58 | in dbSNP:rs61432120 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_060709 | 110 | in dbSNP:rs56348930 | |||
Sequence: G → E | ||||||
Natural variant | VAR_030154 | 112 | in dbSNP:rs11601507 | |||
Sequence: V → F | ||||||
Natural variant | VAR_017398 | 136 | in dbSNP:rs10838525 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_030155 | 249 | in dbSNP:rs11038628 | |||
Sequence: G → D | ||||||
Mutagenesis | 332 | Increases strongly cell restriction against HIV-1 and SIVmac infection. | ||||
Sequence: R → A, G, H, P, Q, or S | ||||||
Mutagenesis | 332 | Increases strongly cell restriction against HIV-1 infection. | ||||
Sequence: R → D, E, or L | ||||||
Mutagenesis | 332 | No effect on HIV-1 and SIVmac infection. | ||||
Sequence: R → K | ||||||
Natural variant | VAR_030156 | 419 | in dbSNP:rs28381981 | |||
Sequence: H → Y | ||||||
Natural variant | VAR_060710 | 467 | in dbSNP:rs59218593 | |||
Sequence: C → S | ||||||
Natural variant | VAR_030157 | 479 | in dbSNP:rs7104422 | |||
Sequence: P → L |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 613 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
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_0000056201 | 2-493 | Tripartite motif-containing protein 5 | |||
Sequence: ASGILVNVKEEVTCPICLELLTQPLSLDCGHSFCQACLTANHKKSMLDKGESSCPVCRISYQPENIRPNRHVANIVEKLREVKLSPEGQKVDHCARHGEKLLLFCQEDGKVICWLCERSQEHRGHHTFLTEEVAREYQVKLQAALEMLRQKQQEAEELEADIREEKASWKTQIQYDKTNVLADFEQLRDILDWEESNELQNLEKEEEDILKSLTNSETEMVQQTQSLRELISDLEHRLQGSVMELLQGVDGVIKRTENVTLKKPETFPKNQRRVFRAPDLKGMLEVFRELTDVRRYWVDVTVAPNNISCAVISEDKRQVSSPKPQIIYGARGTRYQTFVNFNYCTGILGSQSITSGKHYWEVDVSKKTAWILGVCAGFQPDAMCNIEKNENYQPKYGYWVIGLEEGVKCSAFQDSSFHTPSVPFIVPLSVIICPDRVGVFLDYEACTVSFFNITNHGFLIYKFSHCSFSQPVFPYLNPRKCGVPMTLCSPSS | ||||||
Modified residue | 86 | 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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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. 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).
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).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for zinc finger, coiled coil, region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Zinc finger | 15-59 | RING-type | ||||
Sequence: CPICLELLTQPLSLDCGHSFCQACLTANHKKSMLDKGESSCPVCR | ||||||
Zinc finger | 90-132 | B box-type | ||||
Sequence: QKVDHCARHGEKLLLFCQEDGKVICWLCERSQEHRGHHTFLTE | ||||||
Coiled coil | 130-241 | |||||
Sequence: LTEEVAREYQVKLQAALEMLRQKQQEAEELEADIREEKASWKTQIQYDKTNVLADFEQLRDILDWEESNELQNLEKEEEDILKSLTNSETEMVQQTQSLRELISDLEHRLQG | ||||||
Region | 185-198 | Required for interaction with GABARAP and for autophagy | ||||
Sequence: FEQLRDILDWEESN | ||||||
Domain | 281-493 | B30.2/SPRY | ||||
Sequence: LKGMLEVFRELTDVRRYWVDVTVAPNNISCAVISEDKRQVSSPKPQIIYGARGTRYQTFVNFNYCTGILGSQSITSGKHYWEVDVSKKTAWILGVCAGFQPDAMCNIEKNENYQPKYGYWVIGLEEGVKCSAFQDSSFHTPSVPFIVPLSVIICPDRVGVFLDYEACTVSFFNITNHGFLIYKFSHCSFSQPVFPYLNPRKCGVPMTLCSPSS |
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 (PubMed:22482711).
The coiled coil domain is important for higher order multimerization by promoting the initial dimerization (By similarity).
The coiled coil domain is important for higher order multimerization by promoting the initial dimerization (By similarity).
The B30.2/SPRY domain acts as a capsid recognition domain. Polymorphisms in this domain explain the observed species-specific differences among orthologs (PubMed:22482711).
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
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 6 isoforms produced by Alternative splicing.
Q9C035-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameAlpha
- Length493
- Mass (Da)56,338
- Last updated2001-06-01 v1
- Checksum8E61AAFD508AF6C0
Q9C035-2
- NameBeta
- NoteProbable artifact.
Q9C035-3
- NameGamma
Q9C035-4
- NameDelta
Q9C035-5
- NameEpsilon
- SynonymsKappa
Q9C035-6
- NameIota
- NoteHas dominant-negative activity against TRIM5alpha. Does not inhibit HIV-1 replication.
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
E7EQQ5 | E7EQQ5_HUMAN | TRIM5 | 209 | ||
C9JWN8 | C9JWN8_HUMAN | TRIM5 | 72 | ||
A0A804HHS7 | A0A804HHS7_HUMAN | TRIM5 | 265 | ||
H7C134 | H7C134_HUMAN | TRIM5 | 187 |
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 76 | in Ref. 2; BAB55218 | ||||
Sequence: I → L | ||||||
Sequence conflict | 130 | in Ref. 2; BAB55218 | ||||
Sequence: L → P | ||||||
Alternative sequence | VSP_044095 | 249-257 | in isoform Iota | |||
Sequence: GVDGVIKRT → VKSGKKPEH | ||||||
Alternative sequence | VSP_009016 | 249-271 | in isoform Epsilon | |||
Sequence: GVDGVIKRTENVTLKKPETFPKN → DGERDLEEARNFSKKSKESVSSS | ||||||
Alternative sequence | VSP_044096 | 258-493 | in isoform Iota | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_009017 | 272-493 | in isoform Epsilon | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_009014 | 299-326 | in isoform Delta | |||
Sequence: VDVTVAPNNISCAVISEDKRQVSSPKPQ → GWSAMARSRFTATSTSQIQAILLPQPPK | ||||||
Alternative sequence | VSP_009012 | 299-347 | in isoform Gamma | |||
Sequence: VDVTVAPNNISCAVISEDKRQVSSPKPQIIYGARGTRYQTFVNFNYCTG → GKEKSHYHKPPCGLSLLLSLSFRILCSLLGSCFKIYDSPSKTHITYPSL | ||||||
Alternative sequence | VSP_009015 | 327-493 | in isoform Delta | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_009013 | 348-493 | in isoform Gamma | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_009010 | 390-400 | in isoform Beta | |||
Sequence: NENYQPKYGYW → KRFMILLPRHT | ||||||
Alternative sequence | VSP_009011 | 401-493 | in isoform Beta | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF220025 EMBL· GenBank· DDBJ | AAG53479.1 EMBL· GenBank· DDBJ | mRNA | ||
AF220026 EMBL· GenBank· DDBJ | AAG53480.1 EMBL· GenBank· DDBJ | mRNA | ||
AF220027 EMBL· GenBank· DDBJ | AAG53481.1 EMBL· GenBank· DDBJ | mRNA | ||
AF220028 EMBL· GenBank· DDBJ | AAG53482.1 EMBL· GenBank· DDBJ | mRNA | ||
AF220029 EMBL· GenBank· DDBJ | AAG53483.1 EMBL· GenBank· DDBJ | mRNA | ||
AY625000 EMBL· GenBank· DDBJ | AAT48101.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ301444 EMBL· GenBank· DDBJ | ABC00997.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301445 EMBL· GenBank· DDBJ | ABC00998.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301446 EMBL· GenBank· DDBJ | ABC00999.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301447 EMBL· GenBank· DDBJ | ABC01000.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301448 EMBL· GenBank· DDBJ | ABC01001.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301449 EMBL· GenBank· DDBJ | ABC01002.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301450 EMBL· GenBank· DDBJ | ABC01003.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301451 EMBL· GenBank· DDBJ | ABC01004.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301452 EMBL· GenBank· DDBJ | ABC01005.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301453 EMBL· GenBank· DDBJ | ABC01006.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301454 EMBL· GenBank· DDBJ | ABC01007.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301455 EMBL· GenBank· DDBJ | ABC01008.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301456 EMBL· GenBank· DDBJ | ABC01009.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301457 EMBL· GenBank· DDBJ | ABC01010.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301458 EMBL· GenBank· DDBJ | ABC01011.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301459 EMBL· GenBank· DDBJ | ABC01012.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301460 EMBL· GenBank· DDBJ | ABC01013.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301461 EMBL· GenBank· DDBJ | ABC01014.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301462 EMBL· GenBank· DDBJ | ABC01015.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301463 EMBL· GenBank· DDBJ | ABC01016.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301464 EMBL· GenBank· DDBJ | ABC01017.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301465 EMBL· GenBank· DDBJ | ABC01018.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301466 EMBL· GenBank· DDBJ | ABC01019.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301467 EMBL· GenBank· DDBJ | ABC01020.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301468 EMBL· GenBank· DDBJ | ABC01021.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301469 EMBL· GenBank· DDBJ | ABC01022.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301470 EMBL· GenBank· DDBJ | ABC01023.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301471 EMBL· GenBank· DDBJ | ABC01024.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301472 EMBL· GenBank· DDBJ | ABC01025.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301473 EMBL· GenBank· DDBJ | ABC01026.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301474 EMBL· GenBank· DDBJ | ABC01027.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301475 EMBL· GenBank· DDBJ | ABC01028.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301476 EMBL· GenBank· DDBJ | ABC01029.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301477 EMBL· GenBank· DDBJ | ABC01030.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301478 EMBL· GenBank· DDBJ | ABC01031.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301479 EMBL· GenBank· DDBJ | ABC01032.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ301480 EMBL· GenBank· DDBJ | ABC01033.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
DQ288685 EMBL· GenBank· DDBJ | ABB90543.1 EMBL· GenBank· DDBJ | mRNA | ||
JF928461 EMBL· GenBank· DDBJ | AEN14475.1 EMBL· GenBank· DDBJ | mRNA | ||
JF928462 EMBL· GenBank· DDBJ | AEN14476.1 EMBL· GenBank· DDBJ | mRNA | ||
AK027593 EMBL· GenBank· DDBJ | BAB55218.1 EMBL· GenBank· DDBJ | mRNA | ||
AC015691 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471064 EMBL· GenBank· DDBJ | EAW68771.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471064 EMBL· GenBank· DDBJ | EAW68772.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471064 EMBL· GenBank· DDBJ | EAW68774.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471064 EMBL· GenBank· DDBJ | EAW68775.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
EU260465 EMBL· GenBank· DDBJ | ABW96352.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471064 EMBL· GenBank· DDBJ | EAW68776.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471064 EMBL· GenBank· DDBJ | EAW68777.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC021258 EMBL· GenBank· DDBJ | AAH21258.1 EMBL· GenBank· DDBJ | mRNA |