Q6PJ69 · TRI65_HUMAN
- ProteinE3 ubiquitin-protein ligase TRIM65
- GeneTRIM65
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids517 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
E3 ubiquitin ligase that plays a role in several processes including innate immnity, autophagy or inflammation (PubMed:28594402, PubMed:34512673).
Negatively regulates miRNAs by modulating the ubiquitination and stability of TNRC6A, a protein involved in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (PubMed:24778252).
This ubiquitination results in the suppressed expression of miR-138-5p leading to increased autophagy (PubMed:31160576).
Upon enteroviral infection, promotes 'Lys-63'-mediated ubiquitination activation of IFIH1/MDA5 leading to innate signaling cascade (PubMed:28594402).
Mechanistically, selectively recognizes MDA5 filaments that occur on dsRNAs (PubMed:33373584).
Plays also a role in limitation of inflammation through different mechanisms. First, promotes 'Lys-48'-mediated ubiquitination of VCAM1 leading to its degradation and limitation of LPS-induced lung inflammation (PubMed:31310649).
In addition, negatively regulates inflammasome activation by promoting 'lys48'-linked ubiquitination of NLRP3 which is critical for the inhibition of NLRP3 inflammasome activation in resting macrophages (PubMed:34512673).
Negatively regulates miRNAs by modulating the ubiquitination and stability of TNRC6A, a protein involved in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (PubMed:24778252).
This ubiquitination results in the suppressed expression of miR-138-5p leading to increased autophagy (PubMed:31160576).
Upon enteroviral infection, promotes 'Lys-63'-mediated ubiquitination activation of IFIH1/MDA5 leading to innate signaling cascade (PubMed:28594402).
Mechanistically, selectively recognizes MDA5 filaments that occur on dsRNAs (PubMed:33373584).
Plays also a role in limitation of inflammation through different mechanisms. First, promotes 'Lys-48'-mediated ubiquitination of VCAM1 leading to its degradation and limitation of LPS-induced lung inflammation (PubMed:31310649).
In addition, negatively regulates inflammasome activation by promoting 'lys48'-linked ubiquitination of NLRP3 which is critical for the inhibition of NLRP3 inflammasome activation in resting macrophages (PubMed:34512673).
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleoplasm | |
Molecular Function | ubiquitin protein ligase activity | |
Molecular Function | zinc ion binding | |
Biological Process | antiviral innate immune response | |
Biological Process | negative regulation of inflammatory response | |
Biological Process | positive regulation of autophagy | |
Biological Process | positive regulation of interferon-alpha production | |
Biological Process | positive regulation of interferon-beta production | |
Biological Process | positive regulation of protein oligomerization | |
Biological Process | positive regulation of protein phosphorylation | |
Biological Process | protein K48-linked ubiquitination | |
Biological Process | protein K63-linked ubiquitination | |
Biological Process | type I interferon-mediated signaling pathway |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase TRIM65
- 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 accessionQ6PJ69
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_060245 | 222 | in dbSNP:rs7222757 | |||
Sequence: V → G | ||||||
Natural variant | VAR_057224 | 364 | in dbSNP:rs34593741 | |||
Sequence: G → R | ||||||
Natural variant | VAR_057225 | 366 | in dbSNP:rs9892938 | |||
Sequence: G → S | ||||||
Natural variant | VAR_060246 | 509 | in dbSNP:rs3760128 | |||
Sequence: L → P |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 673 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, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000249191 | 2-517 | E3 ubiquitin-protein ligase TRIM65 | |||
Sequence: AAQLLEEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKACPECREPFPDGAELRRNVALSGVLEVVRAGPARDPGPDPGPGPDPAARCPRHGRPLELFCRTEGRCVCSVCTVRECRLHERALLDAERLKREAQLRASLEVTQQQATQAEGQLLELRKQSSQIQNSACILASWVSGKFSSLLQALEIQHTTALRSIEVAKTQALAQARDEEQRLRVHLEAVARHGCRIRELLEQVDEQTFLQESQLLQPPGPLGPLTPLQWDEDQQLGDLKQLLSRLCGLLLEEGSHPGAPAKPVDLAPVEAPGPLAPVPSTVCPLRRKLWQNYRNLTFDPVSANRHFYLSRQDQQVKHCRQSRGPGGPGSFELWQVQCAQSFQAGHHYWEVRASDHSVTLGVSYPQLPRCRLGPHTDNIGRGPCSWGLCVQEDSLQAWHNGEAQRLPGVSGRLLGMDLDLASGCLTFYSLEPQTQPLYTFHALFNQPLTPVFWLLEGRTLTLCHQPGAVFPLGPQEEVLS | ||||||
Modified residue | 185 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 206 | (Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Structure
Family & Domains
Features
Showing features for zinc finger, region, compositional bias, coiled coil, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Zinc finger | 12-51 | RING-type | ||||
Sequence: CAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKACPECR | ||||||
Region | 75-94 | Disordered | ||||
Sequence: AGPARDPGPDPGPGPDPAAR | ||||||
Compositional bias | 80-94 | Pro residues | ||||
Sequence: DPGPDPGPGPDPAAR | ||||||
Zinc finger | 90-137 | B box-type | ||||
Sequence: DPAARCPRHGRPLELFCRTEGRCVCSVCTVRECRLHERALLDAERLKR | ||||||
Coiled coil | 139-227 | |||||
Sequence: AQLRASLEVTQQQATQAEGQLLELRKQSSQIQNSACILASWVSGKFSSLLQALEIQHTTALRSIEVAKTQALAQARDEEQRLRVHLEAV | ||||||
Domain | 313-506 | B30.2/SPRY | ||||
Sequence: APVPSTVCPLRRKLWQNYRNLTFDPVSANRHFYLSRQDQQVKHCRQSRGPGGPGSFELWQVQCAQSFQAGHHYWEVRASDHSVTLGVSYPQLPRCRLGPHTDNIGRGPCSWGLCVQEDSLQAWHNGEAQRLPGVSGRLLGMDLDLASGCLTFYSLEPQTQPLYTFHALFNQPLTPVFWLLEGRTLTLCHQPGAV |
Sequence similarities
Belongs to the TRIM/RBCC family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length517
- Mass (Da)57,353
- Last updated2010-05-18 v3
- Checksum1382A178CB99BBBA
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 80-94 | Pro residues | ||||
Sequence: DPGPDPGPGPDPAAR |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AC087289 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC006138 EMBL· GenBank· DDBJ | AAH06138.1 EMBL· GenBank· DDBJ | mRNA | ||
BC021259 EMBL· GenBank· DDBJ | AAH21259.2 EMBL· GenBank· DDBJ | mRNA | ||
BC073831 EMBL· GenBank· DDBJ | AAH73831.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC098412 EMBL· GenBank· DDBJ | AAH98412.1 EMBL· GenBank· DDBJ | mRNA |