RO52_MOUSE
ID RO52_MOUSE Reviewed; 470 AA.
AC Q62191;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM21;
DE EC=2.3.2.27;
DE AltName: Full=52 kDa Ro protein;
DE AltName: Full=52 kDa ribonucleoprotein autoantigen Ro/SS-A;
DE AltName: Full=RING-type E3 ubiquitin transferase TRIM21 {ECO:0000305};
DE AltName: Full=Ro(SS-A);
DE AltName: Full=Sjoegren syndrome type A antigen;
DE Short=SS-A;
DE AltName: Full=Tripartite motif-containing protein 21;
GN Name=Trim21; Synonyms=Ro52, Ssa1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Macrophage;
RX PubMed=8625517; DOI=10.1046/j.1365-2249.1996.16726.x;
RA Keech C.L., Gordon T.P., McCluskey J.;
RT "Structural differences between the human and mouse 52-kD Ro autoantigens
RT associated with poorly conserved autoantibody activity across species.";
RL Clin. Exp. Immunol. 104:255-263(1996).
RN [2]
RP PROTEIN SEQUENCE OF 226-237; 242-252; 298-308 AND 329-340, FUNCTION,
RP INTERACTION WITH IRF8, AUTOUBIQUITINATION, SUBCELLULAR LOCATION, INDUCTION,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17579016; DOI=10.4049/jimmunol.179.1.26;
RA Kong H.J., Anderson D.E., Lee C.H., Jang M.K., Tamura T., Tailor P.,
RA Cho H.K., Cheong J., Xiong H., Morse H.C. III, Ozato K.;
RT "Autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates
RT IRF-8 and enhances cytokine expression in macrophages.";
RL J. Immunol. 179:26-30(2007).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: E3 ubiquitin-protein ligase whose activity is dependent on E2
CC enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2. Forms a ubiquitin ligase
CC complex in cooperation with the E2 UBE2D2 that is used not only for the
CC ubiquitination of USP4 and IKBKB but also for its self-ubiquitination.
CC Component of cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3
CC ubiquitin-protein ligase complexes such as SCF(SKP2)-like complexes. A
CC TRIM21-containing SCF(SKP2)-like complex is shown to mediate
CC ubiquitination of CDKN1B ('Thr-187' phosphorylated-form), thereby
CC promoting its degradation by the proteasome. Monoubiquitinates IKBKB
CC that will negatively regulates Tax-induced NF-kappa-B signaling.
CC Negatively regulates IFN-beta production post-pathogen recognition by
CC polyubiquitin-mediated degradation of IRF3. Mediates the ubiquitin-
CC mediated proteasomal degradation of IgG1 heavy chain, which is linked
CC to the VCP-mediated ER-associated degradation (ERAD) pathway. Promotes
CC IRF8 ubiquitination, which enhanced the ability of IRF8 to stimulate
CC cytokine genes transcription in macrophages. Plays a role in the
CC regulation of the cell cycle progression. Enhances the decapping
CC activity of DCP2. Exists as a ribonucleoprotein particle present in all
CC mammalian cells studied and composed of a single polypeptide and one of
CC four small RNA molecules. At least two isoforms are present in
CC nucleated and red blood cells, and tissue specific differences in
CC RO/SSA proteins have been identified. The common feature of these
CC proteins is their ability to bind HY RNAs.2. Involved in the regulation
CC of innate immunity and the inflammatory response in response to
CC IFNG/IFN-gamma. Organizes autophagic machinery by serving as a platform
CC for the assembly of ULK1, Beclin 1/BECN1 and ATG8 family members and
CC recognizes specific autophagy targets, thus coordinating target
CC recognition with assembly of the autophagic apparatus and initiation of
CC autophagy. Acts as an autophagy receptor for the degradation of IRF3,
CC hence attenuating type I interferon (IFN)-dependent immune responses
CC (By similarity) (PubMed:17579016). Represses the innate antiviral
CC response by facilitating the formation of the NMI-IFI35 complex through
CC 'Lys-63'-linked ubiquitination of NMI (By similarity).
CC {ECO:0000250|UniProtKB:P19474, ECO:0000269|PubMed:17579016}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homotrimer (By similarity). Component of a SCF(SKP2)-like
CC complex containing CUL1, SKP1, TRIM21 and SKP2. Interacts with CALR,
CC CUL1, FBXW11, HSPA5, IKBKB, IRF3, SKP1 and VCP. Interacts with SKP2;
CC the interaction with SKP2 does not depend on an intact F-box domain.
CC Interacts (via N-terminus and C-terminus) with DCP2 (via N-terminus and
CC C-terminus) (By similarity). Interacts (via C-terminus) with IRF8 (via
CC C-terminus). Interacts with ULK1, BECN1 and with ATG8 family members,
CC including GABARAP, GABARAPL1, GABARAPL2 and MAP1LC3C/LC3C. Interacts
CC with TRIM21 and SQSTM1/sequestosome 1. Interacts with IRF3 (By
CC similarity) (PubMed:17579016). Interacts (via the SPRY domain) with NMI
CC (via coiled-coil domain); the interaction promotes 'Lys-63'-linked
CC ubiquitination of NMI (By similarity). Interacts with IFI35 and NMI;
CC the interaction facilitates NMI-IFI35 complex formation (By
CC similarity). {ECO:0000250|UniProtKB:P19474,
CC ECO:0000269|PubMed:17579016}.
CC -!- INTERACTION:
CC Q62191; Q91VN6: Ddx41; NbExp=6; IntAct=EBI-6840982, EBI-2551902;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17579016}.
CC Cytoplasmic vesicle, autophagosome {ECO:0000250|UniProtKB:O15553}.
CC Nucleus {ECO:0000269|PubMed:17579016}. Cytoplasm, P-body {ECO:0000250}.
CC Note=Enters the nucleus upon exposure to nitric oxide. Localizes to
CC small dot- or rod-like structures in the cytoplasm, called processing
CC bodies (P-bodies) that are located underneath the plasma membrane and
CC also diffusely in the cytoplasm. They are located along the
CC microtubules and are highly motile in cells. Colocalizes with DCP2 in
CC P-bodies. {ECO:0000250|UniProtKB:P19474}.
CC -!- INDUCTION: Up-regulated by IFN. {ECO:0000269|PubMed:17579016}.
CC -!- DOMAIN: The coiled-coil is necessary for the cytoplasmic localization.
CC {ECO:0000250|UniProtKB:P19474}.
CC -!- DOMAIN: The RING-type zinc finger is necessary for ubiquitination and
CC for the IRF3-driven interferon beta promoter activity. Interacts with
CC SKP2 and CUL1 in a RING finger-independent manner. The RING-type zinc
CC finger is necessary for ubiquitination of NMI.
CC {ECO:0000250|UniProtKB:P19474}.
CC -!- DOMAIN: The B30.2/SPRY domain is necessary for the cytoplasmic
CC localization, the interaction with IRF3 and for the IRF3-driven
CC interferon beta promoter activity. The B30.2/SPRY domain is necessary
CC for the interaction with NMI. {ECO:0000250|UniProtKB:P19474}.
CC -!- PTM: Autoubiquitinated; does not lead to its proteasomal degradation.
CC Deubiquitinated by USP4; leading to its stabilization (By similarity).
CC Autoubiquitinated. {ECO:0000250, ECO:0000269|PubMed:17579016}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
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DR EMBL; L27990; AAB51154.1; -; mRNA.
DR PDB; 2VOK; X-ray; 1.30 A; A/B=291-470.
DR PDB; 3ZO0; X-ray; 1.99 A; B=291-470.
DR PDBsum; 2VOK; -.
DR PDBsum; 3ZO0; -.
DR AlphaFoldDB; Q62191; -.
DR SMR; Q62191; -.
DR IntAct; Q62191; 24.
DR STRING; 10090.ENSMUSP00000033264; -.
DR PhosphoSitePlus; Q62191; -.
DR EPD; Q62191; -.
DR MaxQB; Q62191; -.
DR PaxDb; Q62191; -.
DR PeptideAtlas; Q62191; -.
DR PRIDE; Q62191; -.
DR ProteomicsDB; 301631; -.
DR MGI; MGI:106657; Trim21.
DR eggNOG; KOG2177; Eukaryota.
DR InParanoid; Q62191; -.
DR PhylomeDB; Q62191; -.
DR Reactome; R-MMU-3134975; Regulation of innate immune responses to cytosolic DNA.
DR Reactome; R-MMU-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR ChiTaRS; Trim21; mouse.
DR EvolutionaryTrace; Q62191; -.
DR PRO; PR:Q62191; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q62191; protein.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000932; C:P-body; IEA:UniProtKB-SubCell.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; ISO:MGI.
DR GO; GO:0045824; P:negative regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0090086; P:negative regulation of protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0032897; P:negative regulation of viral transcription; ISO:MGI.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IBA:GO_Central.
DR GO; GO:0032092; P:positive regulation of protein binding; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISS:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0032880; P:regulation of protein localization; IBA:GO_Central.
DR GO; GO:0046596; P:regulation of viral entry into host cell; IBA:GO_Central.
DR GO; GO:0034341; P:response to interferon-gamma; ISS:UniProtKB.
DR GO; GO:0044790; P:suppression of viral release by host; ISO:MGI.
DR CDD; cd12900; SPRY_PRY_TRIM21; 1.
DR Gene3D; 2.60.120.920; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR003879; Butyrophylin_SPRY.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR006574; PRY.
DR InterPro; IPR035831; PRY/SPRY_TRIM21.
DR InterPro; IPR003877; SPRY_dom.
DR InterPro; IPR000315; Znf_B-box.
DR InterPro; IPR020457; Znf_B-box_chordata.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF13765; PRY; 1.
DR Pfam; PF00622; SPRY; 1.
DR Pfam; PF00643; zf-B_box; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR PRINTS; PR01406; BBOXZNFINGER.
DR PRINTS; PR01407; BUTYPHLNCDUF.
DR SMART; SM00336; BBOX; 1.
DR SMART; SM00589; PRY; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00449; SPRY; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS50188; B302_SPRY; 1.
DR PROSITE; PS50119; ZF_BBOX; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Coiled coil; Cytoplasm; Cytoplasmic vesicle;
KW Direct protein sequencing; DNA-binding; Metal-binding; Nucleus;
KW Reference proteome; Ribonucleoprotein; RNA-binding; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..470
FT /note="E3 ubiquitin-protein ligase TRIM21"
FT /id="PRO_0000056116"
FT DOMAIN 272..470
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 20..59
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 96..127
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT COILED 188..250
FT /evidence="ECO:0000255"
FT BINDING 96
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 124
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 312..315
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 331..338
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 341..351
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 358..364
FT /evidence="ECO:0007829|PDB:2VOK"
FT TURN 377..380
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 381..387
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 390..393
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 399..401
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 408..415
FT /evidence="ECO:0007829|PDB:2VOK"
FT TURN 416..419
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 420..425
FT /evidence="ECO:0007829|PDB:2VOK"
FT TURN 426..430
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 431..436
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 445..450
FT /evidence="ECO:0007829|PDB:2VOK"
FT STRAND 455..457
FT /evidence="ECO:0007829|PDB:3ZO0"
FT STRAND 463..465
FT /evidence="ECO:0007829|PDB:2VOK"
SQ SEQUENCE 470 AA; 54175 MW; 393AE5AFD254855B CRC64;
MSPSTTSKMS LEKMWEEVTC SICLDPMVEP MSIECGHCFC KECIFEVGKN GGSSCPECRQ
QFLLRNLRPN RHIANMVENL KQIAQNTKKS TQETHCMKHG EKLHLFCEED GQALCWVCAQ
SGKHRDHTRV PIEEAAKVYQ EKIHVVLEKL RKGKELAEKM EMDLTMQRTD WKRNIDTQKS
RIHAEFALQN SLLAQEEQRQ LQRLEKDQRE YLRLLGKKEA ELAEKNQALQ ELISELERRI
RGSELELLQE VRIILERSGS WNLDTLDIDA PDLTSTCPVP GRKKMLRTCW VHITLDRNTA
NSWLIISKDR RQVRMGDTHQ NVSDNKERFS NYPMVLGAQR FSSGKMYWEV DVTQKEAWDL
GVCRDSVQRK GQFSLSPENG FWTIWLWQDS YEAGTSPQTT LHIQVPPCQI GIFVDYEAGV
VSFYNITDHG SLIYTFSECV FAGPLRPFFN VGFNYSGGNA APLKLCPLKM
