Protein: E3 ubiquitin-protein ligase TRIM65 (Q6PJ69)
Organism: Homo sapiens (Human)
Function: E3 ubiquitin ligase that plays a role in several processes including innate immnity, autophagy or inflammation. 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. This ubiquitination results in the suppressed expression of miR-138-5p leading to increased autophagy. Upon enteroviral infection, promotes 'Lys-63'- mediated ubiquitination activation of IFIH1/MDA5 leading to innate signaling cascade. Mechanistically, selectively recognizes MDA5 filaments that occur on dsRNAs. 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. 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
Subcellular location: Cytoplasm
Sequence: MAAQLLEEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKACPECREPFPDGAELRRNVALSGVLEVVRAGPARDPGPDPGPGPDPAARCPRHGRPLELFCRTEGRCVCSVCTVRECRLHERALLDAERLKREAQLRASLEVTQQQATQAEGQLLELRKQSSQIQNSACILASWVSGKFSSLLQALEIQHTTALRSIEVAKTQALAQARDEEQRLRVHLEAVARHGCRIRELLEQVDEQTFLQESQLLQPPGPLGPLTPLQWDEDQQLGDLKQLLSRLCGLLLEEGSHPGAPAKPVDLAPVEAPGPLAPVPSTVCPLRRKLWQNYRNLTFDPVSANRHFYLSRQDQQVKHCRQSRGPGGPGSFELWQVQCAQSFQAGHHYWEVRASDHSVTLGVSYPQLPRCRLGPHTDNIGRGPCSWGLCVQEDSLQAWHNGEAQRLPGVSGRLLGMDLDLASGCLTFYSLEPQTQPLYTFHALFNQPLTPVFWLLEGRTLTLCHQPGAVFPLGPQEEVLS
InterPro domains: - IPR003879: Butyrophylin-like, SPRY domain (domain) [329-491]
- IPR001841: Zinc finger, RING-type (domain) [12-51]
- IPR013320: Concanavalin A-like lectin/glucanase domain superfamily (homologous_superfamily) [311-504]
- IPR000315: B-box-type zinc finger (domain) [90-137]
- IPR018957: Zinc finger, C3HC4 RING-type (domain) [12-50]
- IPR017907: Zinc finger, RING-type, conserved site (conserved_site) [27-36]
- IPR001870: B30.2/SPRY domain (domain) [313-506]
- IPR003877: SPRY domain (domain) [381-503]
- IPR043136: B30.2/SPRY domain superfamily (homologous_superfamily) [316-502]
- IPR048222: E3 ubiquitin-protein ligase TRIM65, PRY/SPRY domain (domain) [322-501]
- IPR051051: E3 ubiquitin-protein ligase TRIM/RNF (family) [93-492]
- IPR013083: Zinc finger, RING/FYVE/PHD-type (homologous_superfamily) [2-76]
- IPR058030: TRIM8/14/16/25/29/45/65, coiled-coil region (domain) [154-289]
Interaction partners: - Interferon-induced helicase C domain-containing protein 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0044238 (primary metabolic process), GO:0071704 (organic substance metabolic process), GO:0043170 (macromolecule metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0019538 (protein metabolic process), GO:0036211 (protein modification process), GO:0043412 (macromolecule modification), GO:0070647 (protein modification by small protein conjugation or removal), GO:0032446 (protein modification by small protein conjugation), GO:0016567 (protein ubiquitination)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)