Full text data of TRIM21
TRIM21
(RNF81, RO52, SSA1)
[Confidence: low (only semi-automatic identification from reviews)]
E3 ubiquitin-protein ligase TRIM21; 6.3.2.- (52 kDa Ro protein; 52 kDa ribonucleoprotein autoantigen Ro/SS-A; RING finger protein 81; Ro(SS-A); Sjoegren syndrome type A antigen; SS-A; Tripartite motif-containing protein 21)
E3 ubiquitin-protein ligase TRIM21; 6.3.2.- (52 kDa Ro protein; 52 kDa ribonucleoprotein autoantigen Ro/SS-A; RING finger protein 81; Ro(SS-A); Sjoegren syndrome type A antigen; SS-A; Tripartite motif-containing protein 21)
UniProt
P19474
ID RO52_HUMAN Reviewed; 475 AA.
AC P19474; Q5XPV5; Q96RF8;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1991, sequence version 1.
DT 22-JAN-2014, entry version 154.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM21;
DE EC=6.3.2.-;
DE AltName: Full=52 kDa Ro protein;
DE AltName: Full=52 kDa ribonucleoprotein autoantigen Ro/SS-A;
DE AltName: Full=RING finger protein 81;
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=RNF81, RO52, SSA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Thymocyte;
RX PubMed=1985094; DOI=10.1172/JCI114968;
RA Itoh K., Itoh Y., Frank M.B.;
RT "Protein heterogeneity in the human Ro/SSA ribonucleoproteins. The 52-
RT and 60-kD Ro/SSA autoantigens are encoded by separate genes.";
RL J. Clin. Invest. 87:177-186(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANT
RP ALA-52.
RX PubMed=1985112; DOI=10.1172/JCI115003;
RA Chan E.K., Hamel J.C., Buyon J.P., Tan E.M.;
RT "Molecular definition and sequence motifs of the 52-kD component of
RT human SS-A/Ro autoantigen.";
RL J. Clin. Invest. 87:68-76(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=7713506; DOI=10.1006/geno.1994.1664;
RA Tsugu H., Horowitz R., Gibson N., Frank M.B.;
RT "The location of a disease-associated polymorphism and genomic
RT structure of the human 52-kDa Ro/SSA locus (SSA1).";
RL Genomics 24:541-548(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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
RT autoantigens associated with poorly conserved autoantibody activity
RT across species.";
RL Clin. Exp. Immunol. 104:255-263(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-96.
RX PubMed=9933563; DOI=10.1006/geno.1998.5659;
RA Bepler G., O'Briant K.C., Kim Y.-C., Schreiber G., Pitterle D.M.;
RT "A 1.4-Mb high-resolution physical map and contig of chromosome
RT segment 11p15.5 and genes in the LOH11A metastasis suppressor
RT region.";
RL Genomics 55:164-175(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Chen Y.-J., Fan Y.-H., Chiou S.-H.;
RT "Isolation of human Sjogren syndrome type A antigen cDNA clone from
RT HEp-2 cells, isolate 1.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
RX PubMed=7561701; DOI=10.1084/jem.182.4.983;
RA Chan E.K., Di Donato F., Hamel J.C., Tseng C.E., Buyon J.P.;
RT "52-kD SS-A/Ro: genomic structure and identification of an
RT alternatively spliced transcript encoding a novel leucine zipper-minus
RT autoantigen expressed in fetal and adult heart.";
RL J. Exp. Med. 182:983-992(1995).
RN [10]
RP INTERACTION WITH CALR.
RX PubMed=8666824;
RA Cheng S.T., Nguyen T.Q., Yang Y.S., Capra J.D., Sontheimer R.D.;
RT "Calreticulin binds hYRNA and the 52-kDa polypeptide component of the
RT Ro/SS-A ribonucleoprotein autoantigen.";
RL J. Immunol. 156:4484-4491(1996).
RN [11]
RP INTERACTION WITH HSPA5.
RX PubMed=12699405; DOI=10.1046/j.1365-2249.2003.02153.x;
RA Purcell A.W., Todd A., Kinoshita G., Lynch T.A., Keech C.L.,
RA Gething M.J., Gordon T.P.;
RT "Association of stress proteins with autoantigens: a possible
RT mechanism for triggering autoimmunity?";
RL Clin. Exp. Immunol. 132:193-200(2003).
RN [12]
RP FUNCTION, AUTOUBIQUITINATION, AND MUTAGENESIS OF CYS-16.
RX PubMed=16297862; DOI=10.1016/j.bbrc.2005.11.029;
RA Wada K., Kamitani T.;
RT "Autoantigen Ro52 is an E3 ubiquitin ligase.";
RL Biochem. Biophys. Res. Commun. 339:415-421(2006).
RN [13]
RP FUNCTION, AND DEUBIQUITINATION BY USP4.
RX PubMed=16316627; DOI=10.1016/j.bbrc.2005.11.076;
RA Wada K., Tanji K., Kamitani T.;
RT "Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase
RT activity.";
RL Biochem. Biophys. Res. Commun. 339:731-736(2006).
RN [14]
RP FUNCTION, AUTOUBIQUITINATION, DEUBIQUITINATION BY USP4, AND
RP MUTAGENESIS OF CYS-16.
RX PubMed=16472766; DOI=10.1016/j.bbrc.2006.01.144;
RA Wada K., Kamitani T.;
RT "UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself.";
RL Biochem. Biophys. Res. Commun. 342:253-258(2006).
RN [15]
RP FUNCTION, AUTOUBIQUITINATION, INTERACTION WITH THE SCF(SKP2)-LIKE
RP COMPLEX, AND INTERACTION WITH SKP2; SKP1; CUL1 AND FBXW11.
RX PubMed=16880511; DOI=10.1128/MCB.01630-05;
RA Sabile A., Meyer A.M., Wirbelauer C., Hess D., Kogel U., Scheffner M.,
RA Krek W.;
RT "Regulation of p27 degradation and S-phase progression by Ro52 RING
RT finger protein.";
RL Mol. Cell. Biol. 26:5994-6004(2006).
RN [16]
RP FUNCTION, INTERACTION WITH DCP2, AND SUBCELLULAR LOCATION.
RX PubMed=18361920; DOI=10.1016/j.bbrc.2008.03.075;
RA Yamochi T., Ohnuma K., Hosono O., Tanaka H., Kanai Y., Morimoto C.;
RT "SSA/Ro52 autoantigen interacts with Dcp2 to enhance its decapping
RT activity.";
RL Biochem. Biophys. Res. Commun. 370:195-199(2008).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, COILED-COIL DOMAIN, AND DOMAIN
RP B30.2/SPRY.
RX PubMed=18845142; DOI=10.1016/j.yexcr.2008.09.011;
RA Espinosa A., Oke V., Elfving A., Nyberg F., Covacu R.,
RA Wahren-Herlenius M.;
RT "The autoantigen Ro52 is an E3 ligase resident in the cytoplasm but
RT enters the nucleus upon cellular exposure to nitric oxide.";
RL Exp. Cell Res. 314:3605-3613(2008).
RN [18]
RP FUNCTION, AND INTERACTION WITH IRF3.
RX PubMed=18641315;
RA Higgs R., Ni Gabhann J., Ben Larbi N., Breen E.P., Fitzgerald K.A.,
RA Jefferies C.A.;
RT "The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production
RT post-pathogen recognition by polyubiquitin-mediated degradation of
RT IRF3.";
RL J. Immunol. 181:1780-1786(2008).
RN [19]
RP FUNCTION, INTERACTION WITH VCP, AUTOUBIQUITINATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18022694; DOI=10.1016/j.molimm.2007.10.023;
RA Takahata M., Bohgaki M., Tsukiyama T., Kondo T., Asaka M.,
RA Hatakeyama S.;
RT "Ro52 functionally interacts with IgG1 and regulates its quality
RT control via the ERAD system.";
RL Mol. Immunol. 45:2045-2054(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP FUNCTION, INTERACTION WITH IKBKB, AND MUTAGENESIS OF CYS-16.
RX PubMed=19675099; DOI=10.1093/jb/mvp127;
RA Wada K., Niida M., Tanaka M., Kamitani T.;
RT "Ro52-mediated monoubiquitination of IKK{beta} down-regulates
RT NF-{kappa}B signalling.";
RL J. Biochem. 146:821-832(2009).
RN [22]
RP ANTIGENICITY.
RX PubMed=20407604;
RA Burbelo P.D., Ching K.H., Han B.L., Bush E.R., Reeves W.H.,
RA Iadarola M.J.;
RT "Extraordinary antigenicity of the human Ro52 autoantigen.";
RL Am. J. Transl. Res. 2:145-155(2010).
RN [23]
RP SUBCELLULAR LOCATION.
RX PubMed=20013343; DOI=10.1007/s00418-009-0669-y;
RA Tanaka M., Tanji K., Niida M., Kamitani T.;
RT "Dynamic movements of Ro52 cytoplasmic bodies along microtubules.";
RL Histochem. Cell Biol. 133:273-284(2010).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: E3 ubiquitin-protein ligase whose activity is dependent
CC on E2 enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2. Forms a
CC ubiquitin ligase complex in cooperation with the E2 UBE2D2 that is
CC used not only for the ubiquitination of USP4 and IKBKB but also
CC for its self-ubiquitination. Component of cullin-RING-based SCF
CC (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes
CC such as SCF(SKP2)-like complexes. A TRIM21-containing SCF(SKP2)-
CC like complex is shown to mediate ubiquitination of CDKN1B ('Thr-
CC 187' phosphorylated-form), thereby promoting its degradation by
CC the proteasome. Monoubiquitinates IKBKB that will negatively
CC regulates Tax-induced NF-kappa-B signaling. Negatively regulates
CC IFN-beta production post-pathogen recognition by polyubiquitin-
CC mediated degradation of IRF3. Mediates the ubiquitin-mediated
CC proteasomal degradation of IgG1 heavy chain, which is linked to
CC the VCP-mediated ER-associated degradation (ERAD) pathway.
CC Promotes IRF8 ubiquitination, which enhanced the ability of IRF8
CC to stimulate cytokine genes transcription in macrophages. Plays a
CC role in the regulation of the cell cycle progression. Enhances the
CC decapping activity of DCP2. Exists as a ribonucleoprotein particle
CC present in all mammalian cells studied and composed of a single
CC polypeptide and one of four small RNA molecules. At least two
CC isoforms are present in nucleated and red blood cells, and tissue
CC specific differences in RO/SSA proteins have been identified. The
CC common feature of these proteins is their ability to bind HY
CC RNAs.2.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts (via C-terminus) with IRF8 (via C-terminus) (By
CC similarity). Component of a SCF(SKP2)-like complex containing
CC CUL1, SKP1, TRIM21 and SKP2. Interacts with CALR, CUL1, FBXW11,
CC HSPA5, IKBKB, IRF3, SKP1 and VCP. Interacts with SKP2; the
CC interaction with SKP2 does not depend on an intact F-box domain.
CC Interacts (via N-terminus and C-terminus) with DCP2 (via N-
CC terminus and C-terminus).
CC -!- INTERACTION:
CC Q13107-1:USP4; NbExp=3; IntAct=EBI-81290, EBI-723305;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cytoplasm, P-body.
CC Note=Enters the nucleus upon exposure to nitric oxide. Localizes
CC to small dot- or rod-like structures in the cytoplasm, called
CC cytoplasmic bodies (P-body) that are located underneath the plasma
CC membrane and also diffusely in the cytoplasm and are highly motil
CC in cells. Cytoplasmic bodies are located along the microtubules
CC and do not share the same cytoplasmic bodies with TRIM5.
CC Colocalizes with DCP2 in P-body.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Ro52alpha, 52alpha;
CC IsoId=P19474-1; Sequence=Displayed;
CC Name=2; Synonyms=Ro52beta, 52beta;
CC IsoId=P19474-2; Sequence=VSP_039627;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in fetal
CC and adult heart and fetal lung.
CC -!- INDUCTION: Up-regulated by isoform 2 of XBP1.
CC -!- DOMAIN: The coiled-coil is necessary for the cytoplasmic
CC localization. The B30.2/SPRY domain is necessary for the
CC cytoplasmic localization, the interaction with IRF3 and for the
CC IRF3-driven interferon beta promoter activity. The RING-type zinc
CC finger is necessary for ubiquitination and for the IRF3-driven
CC interferon beta promoter activity. Interacts with SKP2 and CUL1 in
CC a RING finger-independent manner.
CC -!- PTM: Autoubiquitinated; does not lead to its proteasomal
CC degradation. Deubiquitinated by USP4; leading to its
CC stabilization.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family.
CC -!- SIMILARITY: Contains 1 B box-type zinc finger.
CC -!- SIMILARITY: Contains 1 B30.2/SPRY domain.
CC -!- SIMILARITY: Contains 1 RING-type zinc finger.
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DR EMBL; M34551; AAA36581.1; -; mRNA.
DR EMBL; U01882; AAB87094.1; -; Genomic_DNA.
DR EMBL; M62800; AAA36651.1; -; mRNA.
DR EMBL; U13658; AAA79867.1; -; Genomic_DNA.
DR EMBL; U13657; AAA79867.1; JOINED; Genomic_DNA.
DR EMBL; AF391283; AAK76432.1; -; Genomic_DNA.
DR EMBL; AY742713; AAU89982.1; -; mRNA.
DR EMBL; AC009758; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010861; AAH10861.1; -; mRNA.
DR PIR; A55642; A37241.
DR RefSeq; NP_003132.2; NM_003141.3.
DR UniGene; Hs.532357; -.
DR PDB; 2IWG; X-ray; 2.35 A; B/E=287-465.
DR PDBsum; 2IWG; -.
DR ProteinModelPortal; P19474; -.
DR SMR; P19474; 10-127, 287-465.
DR IntAct; P19474; 28.
DR MINT; MINT-1462811; -.
DR STRING; 9606.ENSP00000254436; -.
DR PhosphoSite; P19474; -.
DR DMDM; 133250; -.
DR PaxDb; P19474; -.
DR PRIDE; P19474; -.
DR DNASU; 6737; -.
DR Ensembl; ENST00000254436; ENSP00000254436; ENSG00000132109.
DR GeneID; 6737; -.
DR KEGG; hsa:6737; -.
DR UCSC; uc001lyy.1; human.
DR CTD; 6737; -.
DR GeneCards; GC11M004406; -.
DR HGNC; HGNC:11312; TRIM21.
DR HPA; CAB004566; -.
DR HPA; HPA005673; -.
DR MIM; 109092; gene.
DR neXtProt; NX_P19474; -.
DR PharmGKB; PA36136; -.
DR eggNOG; NOG276395; -.
DR HOGENOM; HOG000234133; -.
DR HOVERGEN; HBG001357; -.
DR InParanoid; P19474; -.
DR KO; K10651; -.
DR OMA; LEVEIAM; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR EvolutionaryTrace; P19474; -.
DR GeneWiki; TRIM21; -.
DR GenomeRNAi; 6737; -.
DR NextBio; 26280; -.
DR PRO; PR:P19474; -.
DR ArrayExpress; P19474; -.
DR Bgee; P19474; -.
DR CleanEx; HS_TRIM21; -.
DR Genevestigator; P19474; -.
DR GO; GO:0000932; C:cytoplasmic mRNA processing body; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030529; C:ribonucleoprotein complex; TAS:ProtInc.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA: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; TAS:Reactome.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0090086; P:negative regulation of protein deubiquitination; IMP:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0070206; P:protein trimerization; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 4.10.45.10; -; 1.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR003879; Butyrophylin.
DR InterPro; IPR008985; ConA-like_lec_gl_sf.
DR InterPro; IPR006574; PRY.
DR InterPro; IPR018355; SPla/RYanodine_receptor_subgr.
DR InterPro; IPR003877; SPRY_rcpt.
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; Alternative splicing; Cell cycle; Coiled coil;
KW Complete proteome; Cytoplasm; DNA-binding; Ligase; Metal-binding;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome;
KW Ribonucleoprotein; RNA-binding; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1 475 E3 ubiquitin-protein ligase TRIM21.
FT /FTId=PRO_0000056115.
FT DOMAIN 268 465 B30.2/SPRY.
FT ZN_FING 16 55 RING-type.
FT ZN_FING 92 123 B box-type.
FT COILED 128 238 Potential.
FT MOD_RES 266 266 Phosphoserine.
FT VAR_SEQ 169 245 Missing (in isoform 2).
FT /FTId=VSP_039627.
FT VARIANT 52 52 P -> A (in dbSNP:rs1042302).
FT /FTId=VAR_013749.
FT VARIANT 88 88 Q -> K (in dbSNP:rs58403334).
FT /FTId=VAR_061821.
FT VARIANT 96 96 G -> R (in dbSNP:rs2975162).
FT /FTId=VAR_013750.
FT VARIANT 231 231 E -> K (in dbSNP:rs2554934).
FT /FTId=VAR_013751.
FT MUTAGEN 16 16 C->A: Loss of E3 ubiquitin-protein ligase
FT activity. Does not inhibit NF-kappa-B-
FT induced gene expression.
FT CONFLICT 10 10 M -> T (in Ref. 6; AAU89982).
FT CONFLICT 189 189 L -> P (in Ref. 6; AAU89982).
FT CONFLICT 216 216 A -> T (in Ref. 6; AAU89982).
FT CONFLICT 262 262 L -> V (in Ref. 6; AAU89982).
FT CONFLICT 313 313 D -> V (in Ref. 6; AAU89982).
FT TURN 293 295
FT STRAND 300 302
FT STRAND 308 311
FT STRAND 327 329
FT STRAND 331 334
FT STRAND 337 347
FT STRAND 354 360
FT TURN 373 376
FT STRAND 377 383
FT TURN 384 386
FT STRAND 387 390
FT STRAND 396 398
FT STRAND 405 412
FT TURN 413 416
FT STRAND 417 422
FT TURN 423 427
FT STRAND 429 433
FT STRAND 442 447
FT STRAND 460 462
SQ SEQUENCE 475 AA; 54170 MW; DDFF2944AFC629FB CRC64;
MASAARLTMM WEEVTCPICL DPFVEPVSIE CGHSFCQECI SQVGKGGGSV CPVCRQRFLL
KNLRPNRQLA NMVNNLKEIS QEAREGTQGE RCAVHGERLH LFCEKDGKAL CWVCAQSRKH
RDHAMVPLEE AAQEYQEKLQ VALGELRRKQ ELAEKLEVEI AIKRADWKKT VETQKSRIHA
EFVQQKNFLV EEEQRQLQEL EKDEREQLRI LGEKEAKLAQ QSQALQELIS ELDRRCHSSA
LELLQEVIIV LERSESWNLK DLDITSPELR SVCHVPGLKK MLRTCAVHIT LDPDTANPWL
ILSEDRRQVR LGDTQQSIPG NEERFDSYPM VLGAQHFHSG KHYWEVDVTG KEAWDLGVCR
DSVRRKGHFL LSSKSGFWTI WLWNKQKYEA GTYPQTPLHL QVPPCQVGIF LDYEAGMVSF
YNITDHGSLI YSFSECAFTG PLRPFFSPGF NDGGKNTAPL TLCPLNIGSQ GSTDY
//
ID RO52_HUMAN Reviewed; 475 AA.
AC P19474; Q5XPV5; Q96RF8;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1991, sequence version 1.
DT 22-JAN-2014, entry version 154.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM21;
DE EC=6.3.2.-;
DE AltName: Full=52 kDa Ro protein;
DE AltName: Full=52 kDa ribonucleoprotein autoantigen Ro/SS-A;
DE AltName: Full=RING finger protein 81;
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=RNF81, RO52, SSA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Thymocyte;
RX PubMed=1985094; DOI=10.1172/JCI114968;
RA Itoh K., Itoh Y., Frank M.B.;
RT "Protein heterogeneity in the human Ro/SSA ribonucleoproteins. The 52-
RT and 60-kD Ro/SSA autoantigens are encoded by separate genes.";
RL J. Clin. Invest. 87:177-186(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANT
RP ALA-52.
RX PubMed=1985112; DOI=10.1172/JCI115003;
RA Chan E.K., Hamel J.C., Buyon J.P., Tan E.M.;
RT "Molecular definition and sequence motifs of the 52-kD component of
RT human SS-A/Ro autoantigen.";
RL J. Clin. Invest. 87:68-76(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=7713506; DOI=10.1006/geno.1994.1664;
RA Tsugu H., Horowitz R., Gibson N., Frank M.B.;
RT "The location of a disease-associated polymorphism and genomic
RT structure of the human 52-kDa Ro/SSA locus (SSA1).";
RL Genomics 24:541-548(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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
RT autoantigens associated with poorly conserved autoantibody activity
RT across species.";
RL Clin. Exp. Immunol. 104:255-263(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-96.
RX PubMed=9933563; DOI=10.1006/geno.1998.5659;
RA Bepler G., O'Briant K.C., Kim Y.-C., Schreiber G., Pitterle D.M.;
RT "A 1.4-Mb high-resolution physical map and contig of chromosome
RT segment 11p15.5 and genes in the LOH11A metastasis suppressor
RT region.";
RL Genomics 55:164-175(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Chen Y.-J., Fan Y.-H., Chiou S.-H.;
RT "Isolation of human Sjogren syndrome type A antigen cDNA clone from
RT HEp-2 cells, isolate 1.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
RX PubMed=7561701; DOI=10.1084/jem.182.4.983;
RA Chan E.K., Di Donato F., Hamel J.C., Tseng C.E., Buyon J.P.;
RT "52-kD SS-A/Ro: genomic structure and identification of an
RT alternatively spliced transcript encoding a novel leucine zipper-minus
RT autoantigen expressed in fetal and adult heart.";
RL J. Exp. Med. 182:983-992(1995).
RN [10]
RP INTERACTION WITH CALR.
RX PubMed=8666824;
RA Cheng S.T., Nguyen T.Q., Yang Y.S., Capra J.D., Sontheimer R.D.;
RT "Calreticulin binds hYRNA and the 52-kDa polypeptide component of the
RT Ro/SS-A ribonucleoprotein autoantigen.";
RL J. Immunol. 156:4484-4491(1996).
RN [11]
RP INTERACTION WITH HSPA5.
RX PubMed=12699405; DOI=10.1046/j.1365-2249.2003.02153.x;
RA Purcell A.W., Todd A., Kinoshita G., Lynch T.A., Keech C.L.,
RA Gething M.J., Gordon T.P.;
RT "Association of stress proteins with autoantigens: a possible
RT mechanism for triggering autoimmunity?";
RL Clin. Exp. Immunol. 132:193-200(2003).
RN [12]
RP FUNCTION, AUTOUBIQUITINATION, AND MUTAGENESIS OF CYS-16.
RX PubMed=16297862; DOI=10.1016/j.bbrc.2005.11.029;
RA Wada K., Kamitani T.;
RT "Autoantigen Ro52 is an E3 ubiquitin ligase.";
RL Biochem. Biophys. Res. Commun. 339:415-421(2006).
RN [13]
RP FUNCTION, AND DEUBIQUITINATION BY USP4.
RX PubMed=16316627; DOI=10.1016/j.bbrc.2005.11.076;
RA Wada K., Tanji K., Kamitani T.;
RT "Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase
RT activity.";
RL Biochem. Biophys. Res. Commun. 339:731-736(2006).
RN [14]
RP FUNCTION, AUTOUBIQUITINATION, DEUBIQUITINATION BY USP4, AND
RP MUTAGENESIS OF CYS-16.
RX PubMed=16472766; DOI=10.1016/j.bbrc.2006.01.144;
RA Wada K., Kamitani T.;
RT "UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself.";
RL Biochem. Biophys. Res. Commun. 342:253-258(2006).
RN [15]
RP FUNCTION, AUTOUBIQUITINATION, INTERACTION WITH THE SCF(SKP2)-LIKE
RP COMPLEX, AND INTERACTION WITH SKP2; SKP1; CUL1 AND FBXW11.
RX PubMed=16880511; DOI=10.1128/MCB.01630-05;
RA Sabile A., Meyer A.M., Wirbelauer C., Hess D., Kogel U., Scheffner M.,
RA Krek W.;
RT "Regulation of p27 degradation and S-phase progression by Ro52 RING
RT finger protein.";
RL Mol. Cell. Biol. 26:5994-6004(2006).
RN [16]
RP FUNCTION, INTERACTION WITH DCP2, AND SUBCELLULAR LOCATION.
RX PubMed=18361920; DOI=10.1016/j.bbrc.2008.03.075;
RA Yamochi T., Ohnuma K., Hosono O., Tanaka H., Kanai Y., Morimoto C.;
RT "SSA/Ro52 autoantigen interacts with Dcp2 to enhance its decapping
RT activity.";
RL Biochem. Biophys. Res. Commun. 370:195-199(2008).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, COILED-COIL DOMAIN, AND DOMAIN
RP B30.2/SPRY.
RX PubMed=18845142; DOI=10.1016/j.yexcr.2008.09.011;
RA Espinosa A., Oke V., Elfving A., Nyberg F., Covacu R.,
RA Wahren-Herlenius M.;
RT "The autoantigen Ro52 is an E3 ligase resident in the cytoplasm but
RT enters the nucleus upon cellular exposure to nitric oxide.";
RL Exp. Cell Res. 314:3605-3613(2008).
RN [18]
RP FUNCTION, AND INTERACTION WITH IRF3.
RX PubMed=18641315;
RA Higgs R., Ni Gabhann J., Ben Larbi N., Breen E.P., Fitzgerald K.A.,
RA Jefferies C.A.;
RT "The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production
RT post-pathogen recognition by polyubiquitin-mediated degradation of
RT IRF3.";
RL J. Immunol. 181:1780-1786(2008).
RN [19]
RP FUNCTION, INTERACTION WITH VCP, AUTOUBIQUITINATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18022694; DOI=10.1016/j.molimm.2007.10.023;
RA Takahata M., Bohgaki M., Tsukiyama T., Kondo T., Asaka M.,
RA Hatakeyama S.;
RT "Ro52 functionally interacts with IgG1 and regulates its quality
RT control via the ERAD system.";
RL Mol. Immunol. 45:2045-2054(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP FUNCTION, INTERACTION WITH IKBKB, AND MUTAGENESIS OF CYS-16.
RX PubMed=19675099; DOI=10.1093/jb/mvp127;
RA Wada K., Niida M., Tanaka M., Kamitani T.;
RT "Ro52-mediated monoubiquitination of IKK{beta} down-regulates
RT NF-{kappa}B signalling.";
RL J. Biochem. 146:821-832(2009).
RN [22]
RP ANTIGENICITY.
RX PubMed=20407604;
RA Burbelo P.D., Ching K.H., Han B.L., Bush E.R., Reeves W.H.,
RA Iadarola M.J.;
RT "Extraordinary antigenicity of the human Ro52 autoantigen.";
RL Am. J. Transl. Res. 2:145-155(2010).
RN [23]
RP SUBCELLULAR LOCATION.
RX PubMed=20013343; DOI=10.1007/s00418-009-0669-y;
RA Tanaka M., Tanji K., Niida M., Kamitani T.;
RT "Dynamic movements of Ro52 cytoplasmic bodies along microtubules.";
RL Histochem. Cell Biol. 133:273-284(2010).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: E3 ubiquitin-protein ligase whose activity is dependent
CC on E2 enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2. Forms a
CC ubiquitin ligase complex in cooperation with the E2 UBE2D2 that is
CC used not only for the ubiquitination of USP4 and IKBKB but also
CC for its self-ubiquitination. Component of cullin-RING-based SCF
CC (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes
CC such as SCF(SKP2)-like complexes. A TRIM21-containing SCF(SKP2)-
CC like complex is shown to mediate ubiquitination of CDKN1B ('Thr-
CC 187' phosphorylated-form), thereby promoting its degradation by
CC the proteasome. Monoubiquitinates IKBKB that will negatively
CC regulates Tax-induced NF-kappa-B signaling. Negatively regulates
CC IFN-beta production post-pathogen recognition by polyubiquitin-
CC mediated degradation of IRF3. Mediates the ubiquitin-mediated
CC proteasomal degradation of IgG1 heavy chain, which is linked to
CC the VCP-mediated ER-associated degradation (ERAD) pathway.
CC Promotes IRF8 ubiquitination, which enhanced the ability of IRF8
CC to stimulate cytokine genes transcription in macrophages. Plays a
CC role in the regulation of the cell cycle progression. Enhances the
CC decapping activity of DCP2. Exists as a ribonucleoprotein particle
CC present in all mammalian cells studied and composed of a single
CC polypeptide and one of four small RNA molecules. At least two
CC isoforms are present in nucleated and red blood cells, and tissue
CC specific differences in RO/SSA proteins have been identified. The
CC common feature of these proteins is their ability to bind HY
CC RNAs.2.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts (via C-terminus) with IRF8 (via C-terminus) (By
CC similarity). Component of a SCF(SKP2)-like complex containing
CC CUL1, SKP1, TRIM21 and SKP2. Interacts with CALR, CUL1, FBXW11,
CC HSPA5, IKBKB, IRF3, SKP1 and VCP. Interacts with SKP2; the
CC interaction with SKP2 does not depend on an intact F-box domain.
CC Interacts (via N-terminus and C-terminus) with DCP2 (via N-
CC terminus and C-terminus).
CC -!- INTERACTION:
CC Q13107-1:USP4; NbExp=3; IntAct=EBI-81290, EBI-723305;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cytoplasm, P-body.
CC Note=Enters the nucleus upon exposure to nitric oxide. Localizes
CC to small dot- or rod-like structures in the cytoplasm, called
CC cytoplasmic bodies (P-body) that are located underneath the plasma
CC membrane and also diffusely in the cytoplasm and are highly motil
CC in cells. Cytoplasmic bodies are located along the microtubules
CC and do not share the same cytoplasmic bodies with TRIM5.
CC Colocalizes with DCP2 in P-body.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Ro52alpha, 52alpha;
CC IsoId=P19474-1; Sequence=Displayed;
CC Name=2; Synonyms=Ro52beta, 52beta;
CC IsoId=P19474-2; Sequence=VSP_039627;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in fetal
CC and adult heart and fetal lung.
CC -!- INDUCTION: Up-regulated by isoform 2 of XBP1.
CC -!- DOMAIN: The coiled-coil is necessary for the cytoplasmic
CC localization. The B30.2/SPRY domain is necessary for the
CC cytoplasmic localization, the interaction with IRF3 and for the
CC IRF3-driven interferon beta promoter activity. The RING-type zinc
CC finger is necessary for ubiquitination and for the IRF3-driven
CC interferon beta promoter activity. Interacts with SKP2 and CUL1 in
CC a RING finger-independent manner.
CC -!- PTM: Autoubiquitinated; does not lead to its proteasomal
CC degradation. Deubiquitinated by USP4; leading to its
CC stabilization.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family.
CC -!- SIMILARITY: Contains 1 B box-type zinc finger.
CC -!- SIMILARITY: Contains 1 B30.2/SPRY domain.
CC -!- SIMILARITY: Contains 1 RING-type zinc finger.
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DR EMBL; M34551; AAA36581.1; -; mRNA.
DR EMBL; U01882; AAB87094.1; -; Genomic_DNA.
DR EMBL; M62800; AAA36651.1; -; mRNA.
DR EMBL; U13658; AAA79867.1; -; Genomic_DNA.
DR EMBL; U13657; AAA79867.1; JOINED; Genomic_DNA.
DR EMBL; AF391283; AAK76432.1; -; Genomic_DNA.
DR EMBL; AY742713; AAU89982.1; -; mRNA.
DR EMBL; AC009758; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010861; AAH10861.1; -; mRNA.
DR PIR; A55642; A37241.
DR RefSeq; NP_003132.2; NM_003141.3.
DR UniGene; Hs.532357; -.
DR PDB; 2IWG; X-ray; 2.35 A; B/E=287-465.
DR PDBsum; 2IWG; -.
DR ProteinModelPortal; P19474; -.
DR SMR; P19474; 10-127, 287-465.
DR IntAct; P19474; 28.
DR MINT; MINT-1462811; -.
DR STRING; 9606.ENSP00000254436; -.
DR PhosphoSite; P19474; -.
DR DMDM; 133250; -.
DR PaxDb; P19474; -.
DR PRIDE; P19474; -.
DR DNASU; 6737; -.
DR Ensembl; ENST00000254436; ENSP00000254436; ENSG00000132109.
DR GeneID; 6737; -.
DR KEGG; hsa:6737; -.
DR UCSC; uc001lyy.1; human.
DR CTD; 6737; -.
DR GeneCards; GC11M004406; -.
DR HGNC; HGNC:11312; TRIM21.
DR HPA; CAB004566; -.
DR HPA; HPA005673; -.
DR MIM; 109092; gene.
DR neXtProt; NX_P19474; -.
DR PharmGKB; PA36136; -.
DR eggNOG; NOG276395; -.
DR HOGENOM; HOG000234133; -.
DR HOVERGEN; HBG001357; -.
DR InParanoid; P19474; -.
DR KO; K10651; -.
DR OMA; LEVEIAM; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR EvolutionaryTrace; P19474; -.
DR GeneWiki; TRIM21; -.
DR GenomeRNAi; 6737; -.
DR NextBio; 26280; -.
DR PRO; PR:P19474; -.
DR ArrayExpress; P19474; -.
DR Bgee; P19474; -.
DR CleanEx; HS_TRIM21; -.
DR Genevestigator; P19474; -.
DR GO; GO:0000932; C:cytoplasmic mRNA processing body; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030529; C:ribonucleoprotein complex; TAS:ProtInc.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA: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; TAS:Reactome.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0090086; P:negative regulation of protein deubiquitination; IMP:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0070206; P:protein trimerization; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 4.10.45.10; -; 1.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR003879; Butyrophylin.
DR InterPro; IPR008985; ConA-like_lec_gl_sf.
DR InterPro; IPR006574; PRY.
DR InterPro; IPR018355; SPla/RYanodine_receptor_subgr.
DR InterPro; IPR003877; SPRY_rcpt.
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; Alternative splicing; Cell cycle; Coiled coil;
KW Complete proteome; Cytoplasm; DNA-binding; Ligase; Metal-binding;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome;
KW Ribonucleoprotein; RNA-binding; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1 475 E3 ubiquitin-protein ligase TRIM21.
FT /FTId=PRO_0000056115.
FT DOMAIN 268 465 B30.2/SPRY.
FT ZN_FING 16 55 RING-type.
FT ZN_FING 92 123 B box-type.
FT COILED 128 238 Potential.
FT MOD_RES 266 266 Phosphoserine.
FT VAR_SEQ 169 245 Missing (in isoform 2).
FT /FTId=VSP_039627.
FT VARIANT 52 52 P -> A (in dbSNP:rs1042302).
FT /FTId=VAR_013749.
FT VARIANT 88 88 Q -> K (in dbSNP:rs58403334).
FT /FTId=VAR_061821.
FT VARIANT 96 96 G -> R (in dbSNP:rs2975162).
FT /FTId=VAR_013750.
FT VARIANT 231 231 E -> K (in dbSNP:rs2554934).
FT /FTId=VAR_013751.
FT MUTAGEN 16 16 C->A: Loss of E3 ubiquitin-protein ligase
FT activity. Does not inhibit NF-kappa-B-
FT induced gene expression.
FT CONFLICT 10 10 M -> T (in Ref. 6; AAU89982).
FT CONFLICT 189 189 L -> P (in Ref. 6; AAU89982).
FT CONFLICT 216 216 A -> T (in Ref. 6; AAU89982).
FT CONFLICT 262 262 L -> V (in Ref. 6; AAU89982).
FT CONFLICT 313 313 D -> V (in Ref. 6; AAU89982).
FT TURN 293 295
FT STRAND 300 302
FT STRAND 308 311
FT STRAND 327 329
FT STRAND 331 334
FT STRAND 337 347
FT STRAND 354 360
FT TURN 373 376
FT STRAND 377 383
FT TURN 384 386
FT STRAND 387 390
FT STRAND 396 398
FT STRAND 405 412
FT TURN 413 416
FT STRAND 417 422
FT TURN 423 427
FT STRAND 429 433
FT STRAND 442 447
FT STRAND 460 462
SQ SEQUENCE 475 AA; 54170 MW; DDFF2944AFC629FB CRC64;
MASAARLTMM WEEVTCPICL DPFVEPVSIE CGHSFCQECI SQVGKGGGSV CPVCRQRFLL
KNLRPNRQLA NMVNNLKEIS QEAREGTQGE RCAVHGERLH LFCEKDGKAL CWVCAQSRKH
RDHAMVPLEE AAQEYQEKLQ VALGELRRKQ ELAEKLEVEI AIKRADWKKT VETQKSRIHA
EFVQQKNFLV EEEQRQLQEL EKDEREQLRI LGEKEAKLAQ QSQALQELIS ELDRRCHSSA
LELLQEVIIV LERSESWNLK DLDITSPELR SVCHVPGLKK MLRTCAVHIT LDPDTANPWL
ILSEDRRQVR LGDTQQSIPG NEERFDSYPM VLGAQHFHSG KHYWEVDVTG KEAWDLGVCR
DSVRRKGHFL LSSKSGFWTI WLWNKQKYEA GTYPQTPLHL QVPPCQVGIF LDYEAGMVSF
YNITDHGSLI YSFSECAFTG PLRPFFSPGF NDGGKNTAPL TLCPLNIGSQ GSTDY
//
MIM
109092
*RECORD*
*FIELD* NO
109092
*FIELD* TI
*109092 TRIPARTITE MOTIF-CONTAINING PROTEIN 21; TRIM21
;;SJOGREN SYNDROME ANTIGEN A1; SSA1;;
read moreSICCA SYNDROME ANTIGEN A; SSA;;
AUTOANTIGEN Ro/SSA, 52-KD; RO52
*FIELD* TX
CLONING
Ro/SSA is a ribonucleoprotein particle composed of a single polypeptide
and 1 of 4 small RNA molecules. Autoantibodies to Ro/SSA are present in
30 to 50% of patients with systemic lupus erythematosus (SLE; 152700)
and in at least half of patients with primary Sjogren syndrome (270150).
At least 2 distinct Ro/SSA polypeptides exist, a 60-kD form (TROVE2;
600063) and a 52-kD form. Using serum from a lupus patient to screen a
human thymocyte cDNA expression library, Itoh et al. (1991) cloned
TRIM21, which encodes the 52-kD Ro/SSA antigen. The deduced 475-amino
acid protein has a calculated molecular mass of 54.1 kD. It has multiple
N-terminal zinc finger motifs, a central leucine zipper, and a potential
N-glycosylation site. Predicted hydrophobic regions are located at the N
terminus, in the center of the molecule, and at the C terminus. Western
blot analysis of lymphocyte extracts using patient serum confirmed that
TRIM21 had an apparent molecular mass of 52 kD.
James et al. (2007) stated that the human TRIM21 protein contains an
N-terminal RING finger that has E3 ligase activity, followed by a B box,
2 coiled-coil regions, and a long C-terminal PRYSPRY domain that binds
IgG (see 147100) Fc fragments.
GENE FUNCTION
Frank (1999) found that human RO52 expressed in insect cells bound
double-stranded but not single-stranded DNA, and that zinc was required
for binding. Sequencing oligonucleotides bound by RO52 revealed a
purine-rich consensus motif, ARGRGGG(G/C)(A/C)GRNGA, in which R
represents a purine and N indicates no consensus.
BIOCHEMICAL FEATURES
James et al. (2007) solved the crystal structure of the TRIM21 PRYSPRY
domain in complex with Fc to 2.35-angstrom resolution. The PRYSPRY
binding surface was formed by 6 extended loops, and mutation analysis
showed that asp355, trp381, trp383, and phe450 were required for Fc
binding. PRYSPRY bound the CH2-CH3 site of Fc, and the stoichiometry was
2 molecules of PRYSPRY to 1 Fc fragment. Binding between PRYSPRY and Fc
was independent of pH from pH 8 to pH 5, but it was highly salt
sensitive. James et al. (2007) hypothesized that during autoimmune
disease, anti-TRIM21 antibodies bind epitopes in the RING and B-box
domains of TRIM21 via their antigen-binding fragment (Fab) and also bind
to the PRYSPRY domain of TRIM21 via their Fc portions. Simultaneous
binding of Fab and Fc to TRIM21 is likely to occur between distinct
TRIM21 molecules via an antibody bipolar bridging mechanism, a feature
of pathogenic superantigens, and form large crosslinked immune
complexes.
GENE STRUCTURE
Frank et al. (1993) determined that the TRIM21 gene contains at least 3
exons. The exon encoding the putative zinc fingers of the protein is
separate from that encoding the leucine zipper.
MAPPING
By radioisotopic in situ hybridization, Frank et al. (1993) mapped the
TRIM21 gene to chromosome 11p15.5.
MOLECULAR GENETICS
Frank et al. (1993) identified a RFLP of the TRIM21 gene and
demonstrated that it was associated with SLE, primarily in black
Americans.
*FIELD* SA
Schoenlebe et al. (1993)
*FIELD* RF
1. Frank, M. B.: Characterization of DNA binding properties and sequence
specificity of the human 52 kDa Ro/SS-A (Ro52) zinc finger protein. Biochem.
Biophys. Res. Commun. 259: 665-670, 1999.
2. Frank, M. B.; Itoh, K.; Fujisaku, A.; Pontarotti, P.; Mattei, M.-G.;
Neas, B. R.: The mapping of the human 52-kD Ro/SSA autoantigen gene
to human chromosome 11, and its polymorphisms. Am. J. Hum. Genet. 52:
183-191, 1993.
3. Itoh, K.; Itoh, Y.; Frank, M. B.: Protein heterogeneity in the
human Ro/SSA ribonucleoproteins: the 52- and 60-kD Ro/SSA autoantigens
are encoded by separate genes. J. Clin. Invest. 87: 177-186, 1991.
4. James, L. C.; Keeble, A. H.; Khan, Z.; Rhodes, D. A.; Trowsdale,
J.: Structural basis for PRYSPRY-mediated tripartite motif (TRIM)
protein function. Proc. Nat. Acad. Sci. 104: 6200-6205, 2007.
5. Schoenlebe, J.; Buyon, J. P.; Zitelli, B. J.; Friedman, D.; Greco,
M. A.; Knisely, A. S.: Neonatal hemochromatosis associated with maternal
autoantibodies against Ro/SS-A and La/SS-B ribonucleoproteins. Am.
J. Dis. Child. 147: 1072-1075, 1993.
*FIELD* CN
Patricia A. Hartz - updated: 8/25/2008
*FIELD* CD
Victor A. McKusick: 3/1/1993
*FIELD* ED
mgross: 08/27/2008
terry: 8/25/2008
wwang: 2/26/2007
mgross: 2/13/2003
mark: 8/25/1997
jason: 7/28/1994
carol: 12/22/1993
carol: 3/20/1993
carol: 3/1/1993
*RECORD*
*FIELD* NO
109092
*FIELD* TI
*109092 TRIPARTITE MOTIF-CONTAINING PROTEIN 21; TRIM21
;;SJOGREN SYNDROME ANTIGEN A1; SSA1;;
read moreSICCA SYNDROME ANTIGEN A; SSA;;
AUTOANTIGEN Ro/SSA, 52-KD; RO52
*FIELD* TX
CLONING
Ro/SSA is a ribonucleoprotein particle composed of a single polypeptide
and 1 of 4 small RNA molecules. Autoantibodies to Ro/SSA are present in
30 to 50% of patients with systemic lupus erythematosus (SLE; 152700)
and in at least half of patients with primary Sjogren syndrome (270150).
At least 2 distinct Ro/SSA polypeptides exist, a 60-kD form (TROVE2;
600063) and a 52-kD form. Using serum from a lupus patient to screen a
human thymocyte cDNA expression library, Itoh et al. (1991) cloned
TRIM21, which encodes the 52-kD Ro/SSA antigen. The deduced 475-amino
acid protein has a calculated molecular mass of 54.1 kD. It has multiple
N-terminal zinc finger motifs, a central leucine zipper, and a potential
N-glycosylation site. Predicted hydrophobic regions are located at the N
terminus, in the center of the molecule, and at the C terminus. Western
blot analysis of lymphocyte extracts using patient serum confirmed that
TRIM21 had an apparent molecular mass of 52 kD.
James et al. (2007) stated that the human TRIM21 protein contains an
N-terminal RING finger that has E3 ligase activity, followed by a B box,
2 coiled-coil regions, and a long C-terminal PRYSPRY domain that binds
IgG (see 147100) Fc fragments.
GENE FUNCTION
Frank (1999) found that human RO52 expressed in insect cells bound
double-stranded but not single-stranded DNA, and that zinc was required
for binding. Sequencing oligonucleotides bound by RO52 revealed a
purine-rich consensus motif, ARGRGGG(G/C)(A/C)GRNGA, in which R
represents a purine and N indicates no consensus.
BIOCHEMICAL FEATURES
James et al. (2007) solved the crystal structure of the TRIM21 PRYSPRY
domain in complex with Fc to 2.35-angstrom resolution. The PRYSPRY
binding surface was formed by 6 extended loops, and mutation analysis
showed that asp355, trp381, trp383, and phe450 were required for Fc
binding. PRYSPRY bound the CH2-CH3 site of Fc, and the stoichiometry was
2 molecules of PRYSPRY to 1 Fc fragment. Binding between PRYSPRY and Fc
was independent of pH from pH 8 to pH 5, but it was highly salt
sensitive. James et al. (2007) hypothesized that during autoimmune
disease, anti-TRIM21 antibodies bind epitopes in the RING and B-box
domains of TRIM21 via their antigen-binding fragment (Fab) and also bind
to the PRYSPRY domain of TRIM21 via their Fc portions. Simultaneous
binding of Fab and Fc to TRIM21 is likely to occur between distinct
TRIM21 molecules via an antibody bipolar bridging mechanism, a feature
of pathogenic superantigens, and form large crosslinked immune
complexes.
GENE STRUCTURE
Frank et al. (1993) determined that the TRIM21 gene contains at least 3
exons. The exon encoding the putative zinc fingers of the protein is
separate from that encoding the leucine zipper.
MAPPING
By radioisotopic in situ hybridization, Frank et al. (1993) mapped the
TRIM21 gene to chromosome 11p15.5.
MOLECULAR GENETICS
Frank et al. (1993) identified a RFLP of the TRIM21 gene and
demonstrated that it was associated with SLE, primarily in black
Americans.
*FIELD* SA
Schoenlebe et al. (1993)
*FIELD* RF
1. Frank, M. B.: Characterization of DNA binding properties and sequence
specificity of the human 52 kDa Ro/SS-A (Ro52) zinc finger protein. Biochem.
Biophys. Res. Commun. 259: 665-670, 1999.
2. Frank, M. B.; Itoh, K.; Fujisaku, A.; Pontarotti, P.; Mattei, M.-G.;
Neas, B. R.: The mapping of the human 52-kD Ro/SSA autoantigen gene
to human chromosome 11, and its polymorphisms. Am. J. Hum. Genet. 52:
183-191, 1993.
3. Itoh, K.; Itoh, Y.; Frank, M. B.: Protein heterogeneity in the
human Ro/SSA ribonucleoproteins: the 52- and 60-kD Ro/SSA autoantigens
are encoded by separate genes. J. Clin. Invest. 87: 177-186, 1991.
4. James, L. C.; Keeble, A. H.; Khan, Z.; Rhodes, D. A.; Trowsdale,
J.: Structural basis for PRYSPRY-mediated tripartite motif (TRIM)
protein function. Proc. Nat. Acad. Sci. 104: 6200-6205, 2007.
5. Schoenlebe, J.; Buyon, J. P.; Zitelli, B. J.; Friedman, D.; Greco,
M. A.; Knisely, A. S.: Neonatal hemochromatosis associated with maternal
autoantibodies against Ro/SS-A and La/SS-B ribonucleoproteins. Am.
J. Dis. Child. 147: 1072-1075, 1993.
*FIELD* CN
Patricia A. Hartz - updated: 8/25/2008
*FIELD* CD
Victor A. McKusick: 3/1/1993
*FIELD* ED
mgross: 08/27/2008
terry: 8/25/2008
wwang: 2/26/2007
mgross: 2/13/2003
mark: 8/25/1997
jason: 7/28/1994
carol: 12/22/1993
carol: 3/20/1993
carol: 3/1/1993