TRIM21

This gene encodes a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The encoded protein is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus. RoSSA interacts with autoantigens in patients with Sjogren syndrome and systemic lupus erythematosus. Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

TRIM21 Gene(Protein Coding) Tripartite Motif Containing 21

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 (PubMed:26347139, PubMed:16297862, PubMed:16316627, PubMed:16472766, PubMed:16880511, PubMed:18022694, PubMed:18361920, PubMed:18641315, PubMed:18845142, PubMed:19675099).
Represses the innate antiviral response by facilitating the formation of the NMI-IFI35 complex through 'Lys-63'-linked ubiquitination of NMI (PubMed:26342464).

Biological Process cell cycle Source:UniProtKB-KW
Biological Process cellular response to chemical stress Source:Reactome
Biological Process innate immune response Source:UniProtKB1 Publication
Biological Process negative regulation of innate immune response Source:UniProtKB1 Publication
Biological Process negative regulation of NF-kappaB transcription factor activity Source:UniProtKB1 Publication
Biological Process negative regulation of protein deubiquitination Source:UniProtKB1 Publication
Biological Process negative regulation of viral transcription Source:UniProtKB1 Publication
Biological Process positive regulation of autophagy Source:UniProtKB1 Publication
Biological Process positive regulation of cell cycle Source:UniProtKB1 Publication
Biological Process positive regulation of DNA-binding transcription factor activity Source:UniProtKB1 Publication
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signaling Source:GO_Central1 Publication
Biological Process positive regulation of NF-kappaB transcription factor activity Source:GO_Central1 Publication
Biological Process positive regulation of protein binding Source:UniProtKB1 Publication
Biological Process positive regulation of viral entry into host cell Source:Ensembl
Biological Process protein autoubiquitination Source:UniProtKB1 Publication
Biological Process protein destabilization Source:UniProtKB1 Publication
Biological Process protein K63-linked ubiquitination Source:UniProtKB1 Publication
Biological Process protein monoubiquitination Source:UniProtKB2 Publications
Biological Process protein polyubiquitination Source:UniProtKB1 Publication
Biological Process protein ubiquitination Source:UniProtKB3 Publications
Biological Process regulation of gene expression Source:GO_Central1 Publication
Biological Process regulation of protein localization Source:GO_Central1 Publication
Biological Process regulation of type I interferon production Source:Reactome
Biological Process regulation of viral entry into host cell Source:GO_Central1 Publication
Biological Process response to interferon-gamma Source:UniProtKB1 Publication
Biological Process suppression of viral release by host Source:UniProtKB1 Publication

Cytoplasm
Cytoplasmic vesicle, autophagosome
Nucleus
Cytoplasm, P-body
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.

Autoubiquitinated; does not lead to its proteasomal degradation. Deubiquitinated by USP4; leading to its stabilization.