Protein: E3 ubiquitin-protein ligase TRIM21 (EC 2.3.2.27) (52 kDa Ro protein) (52 kDa ribonucleoprotein autoantigen Ro/SS-A) (Ro(SS-A)) (Sjoegren syndrome type A antigen) (SS-A) (Tripartite motif-containing protein 21) (Q62191)
Organism: Mus musculus (Mouse)
Function: E3 ubiquitin-protein ligase whose activity is dependent on E2 enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2. Forms a ubiquitin ligase complex in cooperation with the E2 UBE2D2 that is used not only for the ubiquitination of USP4 and IKBKB but also for its self-ubiquitination. Component of cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes such as SCF(SKP2)-like complexes. A TRIM21-containing SCF(SKP2)-like complex is shown to mediate ubiquitination of CDKN1B ('Thr-187' phosphorylated-form), thereby promoting its degradation by the proteasome. Monoubiquitinates IKBKB that will negatively regulates Tax-induced NF-kappa-B signaling. Negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3. Mediates the ubiquitin-mediated proteasomal degradation of IgG1 heavy chain, which is linked to the VCP-mediated ER-associated degradation (ERAD) pathway. Promotes IRF8 ubiquitination, which enhanced the ability of IRF8 to stimulate cytokine genes transcription in macrophages. Plays a role in the regulation of the cell cycle progression. Enhances the decapping activity of DCP2. Exists as a ribonucleoprotein particle present in all mammalian cells studied and composed of a single polypeptide and one of four small RNA molecules. At least two isoforms are present in nucleated and red blood cells, and tissue specific differences in RO/SSA proteins have been identified. The common feature of these proteins is their ability to bind HY RNAs.2. Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1 and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy. Acts as an autophagy receptor for the degradation of IRF3, hence attenuating type I interferon (IFN)-dependent immune responses (By similarity). Represses the innate antiviral response by facilitating the formation of the NMI-IFI35 complex through 'Lys-63'-linked ubiquitination of NMI (By similarity).
Subcellular location: Cytoplasm {ECO:0000269|PubMed:17579016}. Cytoplasmic vesicle, autophagosome {ECO:0000250|UniProtKB:P19474}. Nucleus {ECO:0000269|PubMed:17579016}. Cytoplasm, P-body {ECO:0000250|UniProtKB:P19474}. Cytoplasm, Stress granule {ECO:0000250|UniProtKB:P19474}. Note=Enters the nucleus upon exposure to nitric oxide. Localizes to small dot- or rod-like structures in the cytoplasm, called processing bodies (P-bodies) that are located underneath the plasma membrane and also diffusely in the cytoplasm. They are located along the microtubules and are highly motile in cells. Colocalizes with DCP2 in P-bodies. Localizes to stress granules in response to oxidative stress. {ECO:0000250|UniProtKB:P19474}.
Interaction partners:
- RNA-binding protein Ro60
- Probable ATP-dependent RNA helicase DDX41
- Interferon regulatory factor 3
- Receptor tyrosine-protein kinase erbB-2
- Ubiquitin carboxyl-terminal hydrolase 4
- Ubiquitin-like protein ISG15
- Ubl carboxyl-terminal hydrolase 18
- Cadherin-1
- Signal transducer and activator of transcription 1
- Interferon-induced helicase C domain-containing protein 1
Sequence:
MSPSTTSKMSLEKMWEEVTCSICLDPMVEPMSIECGHCFCKECIFEVGKNGGSSCPECRQQFLLRNLRPNRHIANMVENLKQIAQNTKKSTQETHCMKHGEKLHLFCEEDGQALCWVCAQSGKHRDHTRVPIEEAAKVYQEKIHVVLEKLRKGKELAEKMEMDLTMQRTDWKRNIDTQKSRIHAEFALQNSLLAQEEQRQLQRLEKDQREYLRLLGKKEAELAEKNQALQELISELERRIRGSELELLQEVRIILERSGSWNLDTLDIDAPDLTSTCPVPGRKKMLRTCWVHITLDRNTANSWLIISKDRRQVRMGDTHQNVSDNKERFSNYPMVLGAQRFSSGKMYWEVDVTQKEAWDLGVCRDSVQRKGQFSLSPENGFWTIWLWQDSYEAGTSPQTTLHIQVPPCQIGIFVDYEAGVVSFYNITDHGSLIYTFSECVFAGPLRPFFNVGFNYSGGNAAPLKLCPLKM