ID:RO52_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase TRIM21; EC=6.3.2.-; AltName: Full=52 kDa Ro protein; AltName: Full=52 kDa ribonucleoprotein autoantigen Ro/SS-A; AltName: Full=RING finger protein 81; AltName: Full=Ro(SS-A); AltName: Full=Sjoegren syndrome type A antigen; Short=SS-A; AltName: Full=Tripartite motif-containing protein 21; 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. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Interacts (via C-terminus) with IRF8 (via C-terminus) (By similarity). Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Interacts with CALR, CUL1, FBXW11, HSPA5, IKBKB, IRF3, SKP1 and VCP. Interacts with SKP2; the interaction with SKP2 does not depend on an intact F-box domain. Interacts (via N-terminus and C-terminus) with DCP2 (via N- terminus and C-terminus). INTERACTION: Q13107-1:USP4; NbExp=3; IntAct=EBI-81290, EBI-723305; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cytoplasm, P-body. Note=Enters the nucleus upon exposure to nitric oxide. Localizes to small dot- or rod-like structures in the cytoplasm, called cytoplasmic bodies (P-body) that are located underneath the plasma membrane and also diffusely in the cytoplasm and are highly motil in cells. Cytoplasmic bodies are located along the microtubules and do not share the same cytoplasmic bodies with TRIM5. Colocalizes with DCP2 in P-body. TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in fetal and adult heart and fetal lung. INDUCTION: Up-regulated by isoform 2 of XBP1. DOMAIN: The coiled-coil is necessary for the cytoplasmic localization. The B30.2/SPRY domain is necessary for the cytoplasmic localization, the interaction with IRF3 and for the IRF3-driven interferon beta promoter activity. The RING-type zinc finger is necessary for ubiquitination and for the IRF3-driven interferon beta promoter activity. Interacts with SKP2 and CUL1 in a RING finger-independent manner. PTM: Autoubiquitinated; does not lead to its proteasomal degradation. Deubiquitinated by USP4; leading to its stabilization. SIMILARITY: Belongs to the TRIM/RBCC family. SIMILARITY: Contains 1 B box-type zinc finger. SIMILARITY: Contains 1 B30.2/SPRY domain. SIMILARITY: Contains 1 RING-type zinc finger.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P19474
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000209 protein polyubiquitination GO:0006513 protein monoubiquitination GO:0007049 cell cycle GO:0010508 positive regulation of autophagy GO:0016567 protein ubiquitination GO:0031648 protein destabilization GO:0032088 negative regulation of NF-kappaB transcription factor activity GO:0032479 regulation of type I interferon production GO:0032897 negative regulation of viral transcription GO:0034341 response to interferon-gamma GO:0045087 innate immune response GO:0045787 positive regulation of cell cycle GO:0046598 positive regulation of viral entry into host cell GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051865 protein autoubiquitination GO:0060333 interferon-gamma-mediated signaling pathway GO:0070206 protein trimerization GO:0090086 negative regulation of protein deubiquitination GO:1902187 negative regulation of viral release from host cell
BC010861 - Homo sapiens tripartite motif-containing 21, mRNA (cDNA clone MGC:9233 IMAGE:3900540), complete cds. AK225564 - Homo sapiens mRNA for 52kD Ro/SSA autoantigen variant, clone: LNF00719. M62800 - Human 52-kD SS-A/Ro autoantigen mRNA, complete cds. M34551 - Human 52-kD ribonucleoprotein Ro/SSA mRNA, complete cds. JD279809 - Sequence 260833 from Patent EP1572962. JD382826 - Sequence 363850 from Patent EP1572962. JD110858 - Sequence 91882 from Patent EP1572962. JD299989 - Sequence 281013 from Patent EP1572962. JD056302 - Sequence 37326 from Patent EP1572962. JD056301 - Sequence 37325 from Patent EP1572962. JD437875 - Sequence 418899 from Patent EP1572962. AY742713 - Homo sapiens Sjogren syndrome antigen A1 mRNA, complete cds. KJ901052 - Synthetic construct Homo sapiens clone ccsbBroadEn_10446 TRIM21 gene, encodes complete protein. EU446706 - Synthetic construct Homo sapiens clone IMAGE:100070204; IMAGE:100011915; FLH257294.01L tripartite motif-containing 21 (TRIM21) gene, encodes complete protein. AB527770 - Synthetic construct DNA, clone: pF1KB5826, Homo sapiens TRIM21 gene for tripartite motif-containing 21, without stop codon, in Flexi system. CU679827 - Synthetic construct Homo sapiens gateway clone IMAGE:100017343 5' read TRIM21 mRNA.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P19474 (Reactome details) participates in the following event(s):
R-HSA-3134946 DDX41 ubiquitination by TRIM21 R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex R-HSA-983147 Release of E3 from polyubiquitinated substrate R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2 R-HSA-3134975 Regulation of innate immune responses to cytosolic DNA R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation R-HSA-877300 Interferon gamma signaling R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA R-HSA-983169 Class I MHC mediated antigen processing & presentation R-HSA-913531 Interferon Signaling R-HSA-168249 Innate Immune System R-HSA-1280218 Adaptive Immune System R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-168256 Immune System
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
