RO52_HUMAN
ID RO52_HUMAN Reviewed; 475 AA.
AC P19474; Q5XPV5; Q96RF8;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 231.
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 finger protein 81;
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 {ECO:0000312|HGNC:HGNC:11312}; Synonyms=RNF81, RO52, SSA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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- and
RT 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 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 human
RT 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 structure of
RT 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 autoantigens
RT associated with poorly conserved autoantibody activity 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 segment
RT 11p15.5 and genes in the LOH11A metastasis suppressor 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 HEp-2
RT 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., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., 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 project:
RT 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 alternatively
RT spliced transcript encoding a novel leucine zipper-minus autoantigen
RT 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., Gething M.J.,
RA Gordon T.P.;
RT "Association of stress proteins with autoantigens: a possible mechanism for
RT 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 MUTAGENESIS OF
RP 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 COMPLEX,
RP 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 finger
RT protein.";
RL Mol. Cell. Biol. 26:5994-6004(2006).
RN [16]
RP HOMOMERIZATION, AND SUBCELLULAR LOCATION.
RX PubMed=17156811; DOI=10.1016/j.virol.2006.10.035;
RA Li X., Gold B., O'hUigin C., Diaz-Griffero F., Song B., Si Z., Li Y.,
RA Yuan W., Stremlau M., Mische C., Javanbakht H., Scally M., Winkler C.,
RA Dean M., Sodroski J.;
RT "Unique features of TRIM5alpha among closely related human TRIM family
RT members.";
RL Virology 360:419-433(2007).
RN [17]
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 [18]
RP FUNCTION, SUBCELLULAR LOCATION, COILED-COIL DOMAIN, AND DOMAIN 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., Wahren-Herlenius M.;
RT "The autoantigen Ro52 is an E3 ligase resident in the cytoplasm but enters
RT the nucleus upon cellular exposure to nitric oxide.";
RL Exp. Cell Res. 314:3605-3613(2008).
RN [19]
RP FUNCTION, AND INTERACTION WITH IRF3.
RX PubMed=18641315; DOI=10.4049/jimmunol.181.3.1780;
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 IRF3.";
RL J. Immunol. 181:1780-1786(2008).
RN [20]
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., Hatakeyama S.;
RT "Ro52 functionally interacts with IgG1 and regulates its quality control
RT via the ERAD system.";
RL Mol. Immunol. 45:2045-2054(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [22]
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 NF-{kappa}B
RT signalling.";
RL J. Biochem. 146:821-832(2009).
RN [23]
RP ANTIGENICITY.
RX PubMed=20407604;
RA Burbelo P.D., Ching K.H., Han B.L., Bush E.R., Reeves W.H., Iadarola M.J.;
RT "Extraordinary antigenicity of the human Ro52 autoantigen.";
RL Am. J. Transl. Res. 2:145-155(2010).
RN [24]
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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP FUNCTION, INDUCTION BY IFNG, INTERACTION WITH MEFV; BECN1; GABARAP;
RP GABARAPL1; GABARAPL2; IRF3; MAP1LC3C; SQSTM1 AND ULK1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=26347139; DOI=10.1083/jcb.201503023;
RA Kimura T., Jain A., Choi S.W., Mandell M.A., Schroder K., Johansen T.,
RA Deretic V.;
RT "TRIM-mediated precision autophagy targets cytoplasmic regulators of innate
RT immunity.";
RL J. Cell Biol. 210:973-989(2015).
RN [29]
RP FUNCTION, INTERACTION WITH NMI AND IFI35, AND DOMAIN.
RX PubMed=26342464; DOI=10.1016/j.virol.2015.08.013;
RA Das A., Dinh P.X., Pattnaik A.K.;
RT "Trim21 regulates Nmi-IFI35 complex-mediated inhibition of innate antiviral
RT response.";
RL Virology 485:383-392(2015).
RN [30]
RP INTERACTION WITH SFTSV VIRUS NSS (MICROBIAL INFECTION).
RX PubMed=31852783; DOI=10.1128/jvi.01684-19;
RA Choi Y., Jiang Z., Shin W.J., Jung J.U.;
RT "Severe Fever with Thrombocytopenia Syndrome Virus NSs Interacts with
RT TRIM21 To Activate the p62-Keap1-Nrf2 Pathway.";
RL J. Virol. 94:0-0(2020).
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 (PubMed:26347139, PubMed:16297862, PubMed:16316627, PubMed:16472766,
CC PubMed:16880511, PubMed:18022694, PubMed:18361920, PubMed:18641315,
CC PubMed:18845142, PubMed:19675099). Represses the innate antiviral
CC response by facilitating the formation of the NMI-IFI35 complex through
CC 'Lys-63'-linked ubiquitination of NMI (PubMed:26342464).
CC {ECO:0000269|PubMed:16297862, ECO:0000269|PubMed:16316627,
CC ECO:0000269|PubMed:16472766, ECO:0000269|PubMed:16880511,
CC ECO:0000269|PubMed:18022694, ECO:0000269|PubMed:18361920,
CC ECO:0000269|PubMed:18641315, ECO:0000269|PubMed:18845142,
CC ECO:0000269|PubMed:19675099, ECO:0000269|PubMed:26342464,
CC ECO:0000269|PubMed:26347139}.
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 (PubMed:17156811) (PubMed:26347139). Interacts (via
CC C-terminus) with IRF8 (via C-terminus) (By similarity). Component of a
CC SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2.
CC Interacts with CALR, CUL1, FBXW11, HSPA5, IKBKB, IRF3, SKP1 and VCP.
CC Interacts with SKP2; the interaction with SKP2 does not depend on an
CC intact F-box domain. Interacts (via N-terminus and C-terminus) with
CC DCP2 (via N-terminus and C-terminus). Interacts with ULK1, BECN1 and
CC with ATG8 family members, including GABARAP, GABARAPL1, GABARAPL2 and
CC MAP1LC3C/LC3C. Interacts with TRIM21 and SQSTM1/sequestosome 1.
CC Interacts with IRF3 (PubMed:26347139, PubMed:12699405, PubMed:16880511,
CC PubMed:17156811, PubMed:18022694, PubMed:18361920, PubMed:18641315,
CC PubMed:19675099, PubMed:8666824) (By similarity). Interacts (via the
CC SPRY domain) with NMI (via coiled-coil domain); the interaction
CC promotes 'Lys-63'-linked ubiquitination of NMI (PubMed:26342464).
CC Interacts with IFI35 and NMI; the interaction facilitates NMI-IFI35
CC complex formation (PubMed:26342464). {ECO:0000250,
CC ECO:0000269|PubMed:12699405, ECO:0000269|PubMed:16880511,
CC ECO:0000269|PubMed:17156811, ECO:0000269|PubMed:18022694,
CC ECO:0000269|PubMed:18361920, ECO:0000269|PubMed:18641315,
CC ECO:0000269|PubMed:19675099, ECO:0000269|PubMed:26342464,
CC ECO:0000269|PubMed:26347139, ECO:0000269|PubMed:8666824}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via B30.2/SPRY domain) with
CC severe fever with thrombocytopenia syndrome virus (SFTSV) NSs; this
CC interaction activates NFE2L2-mediated transcriptional activation of
CC antioxidant genes. {ECO:0000269|PubMed:31852783}.
CC -!- INTERACTION:
CC P19474; O15296: ALOX15B; NbExp=3; IntAct=EBI-81290, EBI-12150557;
CC P19474; O00257-3: CBX4; NbExp=3; IntAct=EBI-81290, EBI-4392727;
CC P19474; Q9NXE8: CWC25; NbExp=3; IntAct=EBI-81290, EBI-746052;
CC P19474; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-81290, EBI-25840379;
CC P19474; Q9NPF5: DMAP1; NbExp=3; IntAct=EBI-81290, EBI-399105;
CC P19474; Q08426: EHHADH; NbExp=3; IntAct=EBI-81290, EBI-2339219;
CC P19474; P17813: ENG; NbExp=6; IntAct=EBI-81290, EBI-2834630;
CC P19474; Q8IYI6: EXOC8; NbExp=3; IntAct=EBI-81290, EBI-742102;
CC P19474; Q9Y613: FHOD1; NbExp=3; IntAct=EBI-81290, EBI-348433;
CC P19474; Q96IK5: GMCL1; NbExp=3; IntAct=EBI-81290, EBI-2548508;
CC P19474; Q13588: GRAP; NbExp=8; IntAct=EBI-81290, EBI-2847510;
CC P19474; P42858: HTT; NbExp=21; IntAct=EBI-81290, EBI-466029;
CC P19474; Q86VF2-5: IGFN1; NbExp=3; IntAct=EBI-81290, EBI-11955401;
CC P19474; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-81290, EBI-739832;
CC P19474; O60260-5: PRKN; NbExp=3; IntAct=EBI-81290, EBI-21251460;
CC P19474; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-81290, EBI-396669;
CC P19474; P37840: SNCA; NbExp=3; IntAct=EBI-81290, EBI-985879;
CC P19474; Q9NUJ3: TCP11L1; NbExp=3; IntAct=EBI-81290, EBI-2555179;
CC P19474; Q8IZW8: TNS4; NbExp=3; IntAct=EBI-81290, EBI-7543499;
CC P19474; P19474: TRIM21; NbExp=8; IntAct=EBI-81290, EBI-81290;
CC P19474; O75382: TRIM3; NbExp=3; IntAct=EBI-81290, EBI-2129889;
CC P19474; Q9HCM9: TRIM39; NbExp=4; IntAct=EBI-81290, EBI-739510;
CC P19474; Q9HCM9-2: TRIM39; NbExp=3; IntAct=EBI-81290, EBI-11523450;
CC P19474; Q99757: TXN2; NbExp=6; IntAct=EBI-81290, EBI-2932492;
CC P19474; Q7KZS0: UBE2I; NbExp=6; IntAct=EBI-81290, EBI-10180829;
CC P19474; P09936: UCHL1; NbExp=3; IntAct=EBI-81290, EBI-714860;
CC P19474; Q9Y4E8: USP15; NbExp=3; IntAct=EBI-81290, EBI-1043104;
CC P19474; Q13107-1: USP4; NbExp=3; IntAct=EBI-81290, EBI-723305;
CC P19474; Q9Y2B5: VPS9D1; NbExp=3; IntAct=EBI-81290, EBI-9031083;
CC P19474; Q6GPH4: XAF1; NbExp=3; IntAct=EBI-81290, EBI-2815120;
CC P19474; Q9BW85: YJU2; NbExp=3; IntAct=EBI-81290, EBI-10300345;
CC P19474; Q05516: ZBTB16; NbExp=3; IntAct=EBI-81290, EBI-711925;
CC P19474; P14240: L; Xeno; NbExp=2; IntAct=EBI-81290, EBI-26968662;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17156811,
CC ECO:0000269|PubMed:26347139}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000269|PubMed:26347139}. Nucleus {ECO:0000269|PubMed:17156811}.
CC Cytoplasm, P-body {ECO:0000269|PubMed:18361920}. Note=Enters the
CC nucleus upon exposure to nitric oxide. Localizes to small dot- or rod-
CC like structures in the cytoplasm, called processing bodies (P-bodies)
CC that are located underneath the plasma membrane and also diffusely in
CC the cytoplasm. They are located along the microtubules and are highly
CC motile in cells. Colocalizes with DCP2 in P-bodies.
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 -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in fetal and
CC adult heart and fetal lung.
CC -!- INDUCTION: Up-regulated by isoform 2 of XBP1. Up-regulated by
CC IFNG/interferon-gamma, with a peak after 2-4 hours of treatment in
CC monocytes/macrophages. {ECO:0000269|PubMed:26347139}.
CC -!- DOMAIN: The coiled-coil is necessary for the cytoplasmic localization.
CC {ECO:0000269|PubMed:18845142}.
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 (PubMed:18845142).
CC The RING-type zinc finger is necessary for ubiquitination of NMI
CC (PubMed:26342464). {ECO:0000269|PubMed:18845142,
CC ECO:0000269|PubMed:26342464}.
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 (PubMed:18845142). The B30.2/SPRY
CC domain is necessary for the interaction with NMI (PubMed:26342464).
CC {ECO:0000269|PubMed:18845142, ECO:0000269|PubMed:26342464}.
CC -!- PTM: Autoubiquitinated; does not lead to its proteasomal degradation.
CC Deubiquitinated by USP4; leading to its stabilization.
CC {ECO:0000269|PubMed:16297862, ECO:0000269|PubMed:16316627,
CC ECO:0000269|PubMed:16472766, ECO:0000269|PubMed:16880511,
CC ECO:0000269|PubMed:18022694}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
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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 CCDS; CCDS44525.1; -. [P19474-1]
DR PIR; A55642; A37241.
DR RefSeq; NP_003132.2; NM_003141.3. [P19474-1]
DR PDB; 2IWG; X-ray; 2.35 A; B/E=287-465.
DR PDB; 5JPX; NMR; -; A=86-130.
DR PDB; 5OLM; X-ray; 1.95 A; A/B=1-129.
DR PDB; 6FGA; X-ray; 2.82 A; A/B/C/D/E/F/G/H=1-98.
DR PDB; 6S53; X-ray; 2.80 A; A/B/G/H=1-85.
DR PDB; 7BBD; X-ray; 2.20 A; B=1-85.
DR PDBsum; 2IWG; -.
DR PDBsum; 5JPX; -.
DR PDBsum; 5OLM; -.
DR PDBsum; 6FGA; -.
DR PDBsum; 6S53; -.
DR PDBsum; 7BBD; -.
DR AlphaFoldDB; P19474; -.
DR SMR; P19474; -.
DR BioGRID; 112615; 229.
DR IntAct; P19474; 77.
DR MINT; P19474; -.
DR STRING; 9606.ENSP00000254436; -.
DR GlyGen; P19474; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P19474; -.
DR PhosphoSitePlus; P19474; -.
DR BioMuta; TRIM21; -.
DR DMDM; 133250; -.
DR EPD; P19474; -.
DR jPOST; P19474; -.
DR MassIVE; P19474; -.
DR MaxQB; P19474; -.
DR PaxDb; P19474; -.
DR PeptideAtlas; P19474; -.
DR PRIDE; P19474; -.
DR ProteomicsDB; 53666; -. [P19474-1]
DR ProteomicsDB; 53667; -. [P19474-2]
DR Antibodypedia; 1469; 407 antibodies from 43 providers.
DR DNASU; 6737; -.
DR Ensembl; ENST00000254436.8; ENSP00000254436.7; ENSG00000132109.10. [P19474-1]
DR GeneID; 6737; -.
DR KEGG; hsa:6737; -.
DR MANE-Select; ENST00000254436.8; ENSP00000254436.7; NM_003141.4; NP_003132.2.
DR UCSC; uc001lyy.2; human. [P19474-1]
DR CTD; 6737; -.
DR DisGeNET; 6737; -.
DR GeneCards; TRIM21; -.
DR HGNC; HGNC:11312; TRIM21.
DR HPA; ENSG00000132109; Low tissue specificity.
DR MIM; 109092; gene.
DR neXtProt; NX_P19474; -.
DR OpenTargets; ENSG00000132109; -.
DR PharmGKB; PA36136; -.
DR VEuPathDB; HostDB:ENSG00000132109; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000161515; -.
DR HOGENOM; CLU_013137_0_3_1; -.
DR InParanoid; P19474; -.
DR OMA; CSQSRKH; -.
DR OrthoDB; 423686at2759; -.
DR PhylomeDB; P19474; -.
DR TreeFam; TF338674; -.
DR PathwayCommons; P19474; -.
DR Reactome; R-HSA-1834941; STING mediated induction of host immune responses.
DR Reactome; R-HSA-3134975; Regulation of innate immune responses to cytosolic DNA.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; P19474; -.
DR SIGNOR; P19474; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 6737; 11 hits in 1122 CRISPR screens.
DR EvolutionaryTrace; P19474; -.
DR GeneWiki; TRIM21; -.
DR GenomeRNAi; 6737; -.
DR Pharos; P19474; Tbio.
DR PRO; PR:P19474; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P19474; protein.
DR Bgee; ENSG00000132109; Expressed in granulocyte and 118 other tissues.
DR ExpressionAtlas; P19474; baseline and differential.
DR Genevisible; P19474; HS.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA: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; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IEA:UniProtKB-SubCell.
DR GO; GO:1990904; C:ribonucleoprotein complex; TAS:ProtInc.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
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; IDA:ARUK-UCL.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase 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; IDA:UniProtKB.
DR GO; GO:0045824; P:negative regulation of innate immune response; IDA:UniProtKB.
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:0032897; P:negative regulation of viral transcription; IDA:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA: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; IMP:UniProtKB.
DR GO; GO:0046598; P:positive regulation of viral entry into host cell; IEA:Ensembl.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IMP:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA: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:0032479; P:regulation of type I interferon production; TAS:Reactome.
DR GO; GO:0046596; P:regulation of viral entry into host cell; IBA:GO_Central.
DR GO; GO:0034341; P:response to interferon-gamma; IDA:UniProtKB.
DR GO; GO:0044790; P:suppression of viral release by host; IDA:UniProtKB.
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; IPR003613; Ubox_domain.
DR InterPro; IPR000315; Znf_B-box.
DR InterPro; IPR020457; Znf_B-box_chordata.
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 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 SMART; SM00504; Ubox; 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; Cytoplasm;
KW Cytoplasmic vesicle; DNA-binding; Host-virus interaction; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Ribonucleoprotein;
KW RNA-binding; Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..475
FT /note="E3 ubiquitin-protein ligase TRIM21"
FT /id="PRO_0000056115"
FT DOMAIN 268..465
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 92..123
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT COILED 128..238
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:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 169..245
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_039627"
FT VARIANT 52
FT /note="P -> A (in dbSNP:rs1042302)"
FT /evidence="ECO:0000269|PubMed:1985112"
FT /id="VAR_013749"
FT VARIANT 88
FT /note="Q -> K (in dbSNP:rs58403334)"
FT /id="VAR_061821"
FT VARIANT 96
FT /note="G -> R (in dbSNP:rs2975162)"
FT /evidence="ECO:0000269|PubMed:9933563"
FT /id="VAR_013750"
FT VARIANT 231
FT /note="E -> K (in dbSNP:rs2554934)"
FT /id="VAR_013751"
FT MUTAGEN 16
FT /note="C->A: Loss of E3 ubiquitin-protein ligase activity.
FT Does not inhibit NF-kappa-B-induced gene expression."
FT /evidence="ECO:0000269|PubMed:16297862,
FT ECO:0000269|PubMed:16472766, ECO:0000269|PubMed:19675099"
FT CONFLICT 10
FT /note="M -> T (in Ref. 6; AAU89982)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="L -> P (in Ref. 6; AAU89982)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="A -> T (in Ref. 6; AAU89982)"
FT /evidence="ECO:0000305"
FT CONFLICT 262
FT /note="L -> V (in Ref. 6; AAU89982)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="D -> V (in Ref. 6; AAU89982)"
FT /evidence="ECO:0000305"
FT TURN 1..3
FT /evidence="ECO:0007829|PDB:7BBD"
FT HELIX 4..13
FT /evidence="ECO:0007829|PDB:5OLM"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:5OLM"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:5OLM"
FT STRAND 24..28
FT /evidence="ECO:0007829|PDB:5OLM"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:5OLM"
FT HELIX 37..44
FT /evidence="ECO:0007829|PDB:5OLM"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:7BBD"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:5OLM"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:7BBD"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:5OLM"
FT HELIX 67..82
FT /evidence="ECO:0007829|PDB:5OLM"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:5OLM"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:5OLM"
FT TURN 104..106
FT /evidence="ECO:0007829|PDB:5OLM"
FT HELIX 112..116
FT /evidence="ECO:0007829|PDB:5OLM"
FT TURN 118..122
FT /evidence="ECO:0007829|PDB:5OLM"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:5OLM"
FT TURN 293..295
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 308..311
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 331..334
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 337..347
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 354..360
FT /evidence="ECO:0007829|PDB:2IWG"
FT TURN 373..376
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 377..383
FT /evidence="ECO:0007829|PDB:2IWG"
FT TURN 384..386
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 387..390
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 396..398
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 405..412
FT /evidence="ECO:0007829|PDB:2IWG"
FT TURN 413..416
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 417..422
FT /evidence="ECO:0007829|PDB:2IWG"
FT TURN 423..427
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 429..433
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 442..447
FT /evidence="ECO:0007829|PDB:2IWG"
FT STRAND 460..462
FT /evidence="ECO:0007829|PDB:2IWG"
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
