Recombinant Mouse E3 ubiquitin-protein ligase TRIM21 (Trim21)

Function

E3 ubiquitin-protein ligase whose activity is dependent on E2 enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2 (By similarity). 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 (By similarity). Component of cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes such as SCF(SKP2)-like complexes (By similarity). 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 (By similarity). Monoubiquitinates IKBKB that will negatively regulates Tax-induced NF-kappa-B signaling (By similarity). Negatively regulates IFN-beta production post-pathogen recognition by catalyzing polyubiquitin-mediated degradation of IRF3 (By similarity). Mediates the ubiquitin-mediated proteasomal degradation of IgG1 heavy chain, which is linked to the VCP-mediated ER-associated degradation (ERAD) pathway (By similarity). Promotes IRF8 ubiquitination, which enhanced the ability of IRF8 to stimulate cytokine genes transcription in macrophages (PubMed:17579016). Plays a role in the regulation of the cell cycle progression (By similarity). Enhances the decapping activity of DCP2 (By similarity). Exists as a ribonucleoprotein particle present in all mammalian cells studied and composed of a single polypeptide and one of four small RNA molecules (By similarity). At least two isoforms are present in nucleated and red blood cells, and tissue specific differences in RO/SSA proteins have been identified (By similarity). The common feature of these proteins is their ability to bind HY RNAs.2 (By similarity). Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma (By similarity). 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 (By similarity). Also regulates autophagy through FIP200/RB1CC1 ubiquitination and subsequent decreased protein stability (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). During viral infection, promotes cell pyroptosis by mediating 'Lys-6'-linked ubiquitination of ISG12a/IFI27, facilitating its translocation into the mitochondria and subsequent CASP3 activation (By similarity). When up-regulated through the IFN/JAK/STAT signaling pathway, promotes 'Lys-27'-linked ubiquitination of MAVS, leading to the recruitment of TBK1 and up-regulation of innate immunity (By similarity). Mediates 'Lys-63'-linked polyubiquitination of G3BP1 in response to heat shock, leading to stress granule disassembly (By similarity)

Subcellular Location

Cytoplasm; Cytoplasmic vesicle, autophagosome; Nucleus; Cytoplasm, P-body; Cytoplasm, Stress granule

Subunit

Homotrimer (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) (By similarity). Interacts (via C-terminus) with IRF8 (via C-terminus). Interacts with ULK1, BECN1 and with ATG8 family members, including GABARAP, GABARAPL1, GABARAPL2 and MAP1LC3C/LC3C. Interacts with TRIM21 and SQSTM1/sequestosome 1. Interacts with IRF3 (By similarity) (PubMed:17579016). Interacts (via the SPRY domain) with NMI (via coiled-coil domain); the interaction promotes 'Lys-63'-linked ubiquitination of NMI (By similarity). Interacts with IFI35 and NMI; the interaction facilitates NMI-IFI35 complex formation (By similarity)

Pathway

Protein modification; protein ubiquitination

• Keech C.L. et al. Structural differences between the human and mouse 52-kD Ro autoantigens associated with poorly conserved autoantibody activity across species. — Clin. Exp. Immunol. (1996)
• Kong H.J. et al. Autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages. — J. Immunol. (2007)
• Huttlin E.L. et al. A tissue-specific atlas of mouse protein phosphorylation and expression. — Cell (2010)