RO52_BOVIN
ID RO52_BOVIN Reviewed; 469 AA.
AC Q7YRV4; A4FV39;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 126.
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;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=14534436; DOI=10.1097/00001756-200310060-00021;
RA Shusta E.V., Li J.Y., Boado R.J., Pardridge W.M.;
RT "The Ro52/SS-A autoantigen has elevated expression at the brain
RT microvasculature.";
RL NeuroReport 14:1861-1865(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hippocampus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
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). Represses the innate antiviral response by
CC facilitating the formation of the NMI-IFI35 complex through 'Lys-63'-
CC linked ubiquitination of NMI (By similarity).
CC {ECO:0000250|UniProtKB:P19474}.
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. Interacts (via C-terminus) with IRF8 (via C-
CC terminus). Component of a SCF(SKP2)-like complex containing CUL1, SKP1,
CC TRIM21 and SKP2. Interacts with CALR, CUL1, FBXW11, HSPA5, IKBKB, IRF3,
CC SKP1 and VCP. Interacts with SKP2; the interaction with SKP2 does not
CC depend on an intact F-box domain. Interacts (via N-terminus and C-
CC terminus) with DCP2 (via N-terminus and C-terminus). Interacts with
CC ULK1, BECN1 and with ATG8 family members, including GABARAP, GABARAPL1,
CC GABARAPL2 and MAP1LC3C/LC3C. Interacts with TRIM21 and
CC SQSTM1/sequestosome 1. Interacts with IRF3 (By similarity). Interacts
CC (via the SPRY domain) with NMI (via coiled-coil domain); the
CC interaction promotes 'Lys-63'-linked ubiquitination of NMI (By
CC similarity). Interacts with IFI35 and NMI; the interaction facilitates
CC NMI-IFI35 complex formation (By similarity).
CC {ECO:0000250|UniProtKB:P19474}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P19474}.
CC Cytoplasmic vesicle, autophagosome {ECO:0000250|UniProtKB:O15553}.
CC Nucleus {ECO:0000250|UniProtKB:P19474}. Cytoplasm, P-body
CC {ECO:0000250}. Note=Enters the nucleus upon exposure to nitric oxide.
CC Localizes to small dot- or rod-like structures in the cytoplasm, called
CC processing bodies (P-bodies) that are located underneath the plasma
CC membrane and also diffusely in the cytoplasm. They are located along
CC the microtubules and are highly motile in cells. Colocalizes with DCP2
CC in P-bodies. {ECO:0000250|UniProtKB:P19474}.
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 {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY312278; AAP79314.1; -; mRNA.
DR EMBL; BT021885; AAX46732.1; -; mRNA.
DR EMBL; BC123700; AAI23701.1; -; mRNA.
DR RefSeq; NP_872596.1; NM_182655.2.
DR RefSeq; XP_005216209.1; XM_005216152.3.
DR AlphaFoldDB; Q7YRV4; -.
DR SMR; Q7YRV4; -.
DR STRING; 9913.ENSBTAP00000054004; -.
DR PRIDE; Q7YRV4; -.
DR Ensembl; ENSBTAT00000018459; ENSBTAP00000018459; ENSBTAG00000013900.
DR GeneID; 359715; -.
DR KEGG; bta:359715; -.
DR CTD; 6737; -.
DR VEuPathDB; HostDB:ENSBTAG00000013900; -.
DR VGNC; VGNC:36319; TRIM21.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000161515; -.
DR HOGENOM; CLU_013137_0_3_1; -.
DR InParanoid; Q7YRV4; -.
DR OMA; CSQSRKH; -.
DR OrthoDB; 423686at2759; -.
DR Reactome; R-BTA-3134975; Regulation of innate immune responses to cytosolic DNA.
DR Reactome; R-BTA-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-BTA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000009136; Chromosome 15.
DR Bgee; ENSBTAG00000013900; Expressed in leukocyte and 107 other tissues.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
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; IEA:Ensembl.
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; IBA:GO_Central.
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; IEA:Ensembl.
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: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:0046598; P:positive regulation of viral entry into host cell; IEA:Ensembl.
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; IEA:Ensembl.
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 2: Evidence at transcript level;
KW Cell cycle; Coiled coil; Cytoplasm; Cytoplasmic vesicle; DNA-binding;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Ribonucleoprotein; RNA-binding; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..469
FT /note="E3 ubiquitin-protein ligase TRIM21"
FT /id="PRO_0000246175"
FT DOMAIN 268..467
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 16..55
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 87..128
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT COILED 128..245
FT /evidence="ECO:0000255"
FT BINDING 92
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 95
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 114
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 120
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19474"
SQ SEQUENCE 469 AA; 54031 MW; 5BB6BB96E7BDE772 CRC64;
MASAVPLTMM WEEVTCSICL DPMVEPMSIE CGHSFCQECI SEVGKEGGSV CPVCRRHFLL
QNLRPNRQVA NMVDNLRKIS QGAKESPHGE LCVVHREKIH LFCEEDGKAL CWVCSQSQKH
RDHPMVPIEE AAQEYQEKLQ VALNKLRHKQ ELAEKLELDI AMKKASWKGK VEAHKLRIHE
EFVRQKNFLA EEEQKQLQKL EEEERQQLRT LGDTEARLAQ QIQALQELIA ELERRRRGSA
LELLQEVKSV LERSESWNLK ELDVASTDLR NVFYVPGIKK MLRTCGVHIT LDPQTANPWL
ILSENRRQVR LANTRQEVPE NEERFDSYPM VLGAQRFDSG KVYWEVDVTG KEAWDLGVCR
DNVRRKGQFL LNSDTGFWII WLWNKQKYEA GTCPQTPLHL QVPPNRIGIF LDYEASTVSF
YNITDHASLI YTFSECAFAG PLRPFFNPGF NDRGTNSAPL ILCPLKTGW
