Protein: E3 ubiquitin-protein ligase TRIM65 (Q8BFW4)
Organism: Mus musculus (Mouse)
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 (By similarity). 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 (By similarity). Also plays 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: MAAQLLEEDVVTCSICLGRYRDPVTLPCGHSFCGNCIQDSWRSCEKSCPECRQPFPEGAKLSRNVKMSTLLQALPVLPAPPAVTPRRDSATSHSARCLRHGRPLEFFCRTEGLCVCSACTVHDCSHHERALLDVERRVREDQLRARVLVTQQQVAQAETQLQELQEQRSRIESSACTLASVVSRRFSSLLQALEKQQASTLSDIEVAKKQALGQVLNEKQRLTDHLRALSQYDQSVQDLLAQADDCIFFQELQQLPEPTESLGPLTSPQWNEEQQLSNVNQLLSPLCELLLEEKSLPKVAAKAADAGPLETLGPLAPVPSAVCPLRKKLWQNYRNLTFDPETANQYLHLSHKDQRVTHHFQAQGPAKSGSFELWQVQCTQSFQTGQHYWEVRVSDHSVTLGVTYPKLSRQKLGTHTDNIGRGPCSWGLCIQEDSMQAWHNGKSQRLRGLPGQLLGVDLNLTSGCLTFYSLEPRTQPLHTFYAVFSQPLFPVFWLLEGRTLTLCHQPEATLPARPQEEATAPS
InterPro domains: - IPR003879: Butyrophylin-like, SPRY domain (domain) [332-494]
- IPR001841: Zinc finger, RING-type (domain) [13-52]
- IPR013320: Concanavalin A-like lectin/glucanase domain superfamily (homologous_superfamily) [326-503]
- IPR018957: Zinc finger, C3HC4 RING-type (domain) [13-51]
- IPR006574: SPRY-associated (domain) [333-383]
- IPR001870: B30.2/SPRY domain (domain) [316-509]
- IPR017907: Zinc finger, RING-type, conserved site (conserved_site) [28-37]
- IPR003877: SPRY domain (domain) [384-506]
- IPR043136: B30.2/SPRY domain superfamily (homologous_superfamily) [320-505]
- IPR048222: E3 ubiquitin-protein ligase TRIM65, PRY/SPRY domain (domain) [325-504]
- IPR051051: E3 ubiquitin-protein ligase TRIM/RNF (family) [93-495]
- IPR013083: Zinc finger, RING/FYVE/PHD-type (homologous_superfamily) [2-76]
- IPR058030: TRIM8/14/16/25/29/45/65, coiled-coil region (domain) [156-292]
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:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0042592 (homeostatic process), GO:0032502 (developmental process), GO:0002376 (immune system process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0032501 (multicellular organismal process), GO:0009605 (response to external stimulus), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0043903 (regulation of biological process involved in symbiotic interaction), GO:0009607 (response to biotic stimulus), GO:0006955 (immune response), GO:0050792 (regulation of viral process), GO:0006950 (response to stress), GO:0048525 (negative regulation of viral process), GO:0048871 (multicellular organismal-level homeostasis), GO:0002262 (myeloid cell homeostasis), GO:0051707 (response to other organism), GO:0043207 (response to external biotic stimulus), GO:1903900 (regulation of viral life cycle), GO:0034101 (erythrocyte homeostasis), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0006952 (defense response), GO:0052372 (modulation by symbiont of entry into host), GO:1903901 (negative regulation of viral life cycle), GO:0045087 (innate immune response), GO:0098542 (defense response to other organism), GO:0048872 (homeostasis of number of cells), GO:0046596 (regulation of viral entry into host cell), GO:0030097 (hemopoiesis), GO:0030218 (erythrocyte differentiation), GO:0046597 (negative regulation of viral entry into host cell), GO:0030099 (myeloid cell differentiation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005622 (intracellular anatomical structure)