TRIM65
E3 ubiquitin-protein ligase TRIM65
Also known as: TRI65_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q6PJ69
- Gene
- TRIM65
- Ensembl
- ENSG00000141569
- Chromosome
- 17
- Canonical length
- 517 aa
- Protein class
- Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Vesicles,Cytosol
OverviewNCBI Gene
Enables ubiquitin protein ligase activity. Involved in negative regulation of inflammatory response; positive regulation of metabolic process; and protein polyubiquitination. Located in cytosol and nucleoplasm. Is active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2025]
Canonical amino-acid sequenceUniProt
517 residues, UniProt reviewed canonical sequence.
>Q6PJ69|TRIM65
1 MAAQLLEEKL TCAICLGLYQ DPVTLPCGHN FCGACIRDWW DRCGKACPEC REPFPDGAEL
61 RRNVALSGVL EVVRAGPARD PGPDPGPGPD PAARCPRHGR PLELFCRTEG RCVCSVCTVR
121 ECRLHERALL DAERLKREAQ LRASLEVTQQ QATQAEGQLL ELRKQSSQIQ NSACILASWV
181 SGKFSSLLQA LEIQHTTALR SIEVAKTQAL AQARDEEQRL RVHLEAVARH GCRIRELLEQ
241 VDEQTFLQES QLLQPPGPLG PLTPLQWDED QQLGDLKQLL SRLCGLLLEE GSHPGAPAKP
301 VDLAPVEAPG PLAPVPSTVC PLRRKLWQNY RNLTFDPVSA NRHFYLSRQD QQVKHCRQSR
361 GPGGPGSFEL WQVQCAQSFQ AGHHYWEVRA SDHSVTLGVS YPQLPRCRLG PHTDNIGRGP
421 CSWGLCVQED SLQAWHNGEA QRLPGVSGRL LGMDLDLASG CLTFYSLEPQ TQPLYTFHAL
481 FNQPLTPVFW LLEGRTLTLC HQPGAVFPLG PQEEVLSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against TRIM65 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.38
- Highest tissue expression
- 20 nTPM
Expression across tissuesHPA
Tissue
- cerebellum: 20 nTPM
- spleen: 16 nTPM
- pancreas: 15 nTPM
- endometrium: 14 nTPM
- cervix: 14 nTPM
- skin: 14 nTPM
Single-cell type
- alveolar cells type 1: 24 nCPM
- myonuclei: 23 nCPM
- paneth cells: 23 nCPM
- retinal pigment epithelial cells: 21 nCPM
- gonadotrophs: 21 nCPM
- retinal bipolar cells: 21 nCPM
Immune cell
- MAIT T-cell: 2.2 nTPM
- naive B-cell: 2 nTPM
- NK-cell: 2 nTPM
- gdT-cell: 1.9 nTPM
- memory CD8 T-cell: 1.9 nTPM
- eosinophil: 1.8 nTPM
Brain region
- white matter: 27 nTPM
- cerebellum: 24 nTPM
- medulla oblongata: 24 nTPM
- basal ganglia: 24 nTPM
- midbrain: 24 nTPM
- cerebral cortex: 23 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.84
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.41
- DepMap mean gene effect
- -0.17
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- antiviral innate immune response
- negative regulation of inflammatory response
- negative regulation of NLRP3 inflammasome complex assembly
- positive regulation of autophagy
- positive regulation of interferon-alpha production
- positive regulation of interferon-beta production
- positive regulation of protein oligomerization
- protein K48-linked ubiquitination
- protein K63-linked ubiquitination
- type I interferon-mediated signaling pathway
Molecular functions
- protein domain specific binding
- ubiquitin protein ligase activity
- ubiquitin-protein transferase activity
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- B-box-type zinc finger
- Zinc finger, RING-type
- B30.2/SPRY domain
- SPRY domain
- Butyrophylin-like, SPRY domain
- Zinc finger, RING/FYVE/PHD-type
- Concanavalin A-like lectin/glucanase domain superfamily
- Zinc finger, RING-type, conserved site
- Zinc finger, C3HC4 RING-type
- B30.2/SPRY domain superfamily
- E3 ubiquitin-protein ligase TRIM/RNF
- TRIM8/14/16/25/29/45/65, coiled-coil region
- Zinc finger, C3HC4 type (RING finger)
- SPRY domain
- B-box zinc finger
- TRIM protein coiled-coil region
- E3 ubiquitin-protein ligase TRIM65, PRY/SPRY domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of TRIM65 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads TRIM65 as an antibody target. Whether an autoantibody or antibody against TRIM65 could matter depends on whether native TRIM65 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
TRIM65 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label TRIM65 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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