TRIM4_HUMAN
ID TRIM4_HUMAN Reviewed; 500 AA.
AC Q9C037; A4D298; Q75MK1; Q96F06; Q9C036;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM4;
DE EC=2.3.2.27;
DE AltName: Full=RING finger protein 87;
DE AltName: Full=RING-type E3 ubiquitin transferase TRIM4 {ECO:0000305};
DE AltName: Full=Tripartite motif-containing protein 4;
GN Name=TRIM4; Synonyms=RNF87;
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] (ISOFORMS ALPHA AND BETA).
RX PubMed=11331580; DOI=10.1093/emboj/20.9.2140;
RA Reymond A., Meroni G., Fantozzi A., Merla G., Cairo S., Luzi L.,
RA Riganelli D., Zanaria E., Messali S., Cainarca S., Guffanti A., Minucci S.,
RA Pelicci P.G., Ballabio A.;
RT "The tripartite motif family identifies cell compartments.";
RL EMBO J. 20:2140-2151(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA).
RC TISSUE=Melanoma;
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 [6]
RP SUBUNIT, 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 [7]
RP FUNCTION, PATHWAY, AND MUTAGENESIS OF CYS-27.
RX PubMed=24755855; DOI=10.1093/jmcb/mju005;
RA Yan J., Li Q., Mao A.P., Hu M.M., Shu H.B.;
RT "TRIM4 modulates type I interferon induction and cellular antiviral
RT response by targeting RIG-I for K63-linked ubiquitination.";
RL J. Mol. Cell Biol. 6:154-163(2014).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: E3 ubiquitin-protein ligase. Mediates 'Lys-63'-linked
CC polyubiquitination of the innate immune receptor DDX58, this linkage
CC doesn't lead to proteasomal degradation but seems to enhance IFN
CC induction. {ECO:0000269|PubMed:24755855}.
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. {ECO:0000269|PubMed:17156811}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17156811}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Alpha;
CC IsoId=Q9C037-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=Q9C037-2; Sequence=VSP_010197;
CC Name=Gamma;
CC IsoId=Q9C037-3; Sequence=VSP_010197, VSP_010198, VSP_010199;
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
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DR EMBL; AF220023; AAG53477.1; -; mRNA.
DR EMBL; AF220024; AAG53478.1; -; mRNA.
DR EMBL; AC011904; AAS07396.1; -; Genomic_DNA.
DR EMBL; AC011904; AAS07398.1; -; Genomic_DNA.
DR EMBL; AC011904; AAS07397.1; -; Genomic_DNA.
DR EMBL; CH236956; EAL23864.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76625.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76626.1; -; Genomic_DNA.
DR EMBL; CH236956; EAL23865.1; -; Genomic_DNA.
DR EMBL; BC011763; AAH11763.1; -; mRNA.
DR EMBL; BC025949; AAH25949.1; -; mRNA.
DR CCDS; CCDS5678.1; -. [Q9C037-2]
DR CCDS; CCDS5679.1; -. [Q9C037-1]
DR RefSeq; NP_148977.2; NM_033017.3. [Q9C037-1]
DR RefSeq; NP_149082.1; NM_033091.2. [Q9C037-2]
DR AlphaFoldDB; Q9C037; -.
DR SMR; Q9C037; -.
DR BioGRID; 124585; 48.
DR IntAct; Q9C037; 13.
DR STRING; 9606.ENSP00000348216; -.
DR iPTMnet; Q9C037; -.
DR PhosphoSitePlus; Q9C037; -.
DR SwissPalm; Q9C037; -.
DR BioMuta; TRIM4; -.
DR DMDM; 209572691; -.
DR EPD; Q9C037; -.
DR jPOST; Q9C037; -.
DR MassIVE; Q9C037; -.
DR MaxQB; Q9C037; -.
DR PaxDb; Q9C037; -.
DR PeptideAtlas; Q9C037; -.
DR PRIDE; Q9C037; -.
DR ProteomicsDB; 79957; -. [Q9C037-1]
DR ProteomicsDB; 79958; -. [Q9C037-2]
DR ProteomicsDB; 79959; -. [Q9C037-3]
DR Antibodypedia; 16291; 221 antibodies from 27 providers.
DR DNASU; 89122; -.
DR Ensembl; ENST00000349062.7; ENSP00000275736.4; ENSG00000146833.16. [Q9C037-2]
DR Ensembl; ENST00000354241.5; ENSP00000346186.5; ENSG00000146833.16. [Q9C037-3]
DR Ensembl; ENST00000355947.6; ENSP00000348216.2; ENSG00000146833.16. [Q9C037-1]
DR GeneID; 89122; -.
DR KEGG; hsa:89122; -.
DR MANE-Select; ENST00000349062.7; ENSP00000275736.4; NM_033091.3; NP_149082.1. [Q9C037-2]
DR UCSC; uc003usd.4; human. [Q9C037-1]
DR CTD; 89122; -.
DR DisGeNET; 89122; -.
DR GeneCards; TRIM4; -.
DR HGNC; HGNC:16275; TRIM4.
DR HPA; ENSG00000146833; Low tissue specificity.
DR neXtProt; NX_Q9C037; -.
DR OpenTargets; ENSG00000146833; -.
DR PharmGKB; PA38108; -.
DR VEuPathDB; HostDB:ENSG00000146833; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000163330; -.
DR HOGENOM; CLU_013137_0_3_1; -.
DR InParanoid; Q9C037; -.
DR OMA; VGVCQED; -.
DR OrthoDB; 423686at2759; -.
DR PhylomeDB; Q9C037; -.
DR TreeFam; TF338674; -.
DR PathwayCommons; Q9C037; -.
DR Reactome; R-HSA-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta.
DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR Reactome; R-HSA-918233; TRAF3-dependent IRF activation pathway.
DR Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR Reactome; R-HSA-933543; NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9C037; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 89122; 16 hits in 1112 CRISPR screens.
DR ChiTaRS; TRIM4; human.
DR GenomeRNAi; 89122; -.
DR Pharos; Q9C037; Tbio.
DR PRO; PR:Q9C037; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9C037; protein.
DR Bgee; ENSG00000146833; Expressed in buccal mucosa cell and 195 other tissues.
DR ExpressionAtlas; Q9C037; baseline and differential.
DR Genevisible; Q9C037; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; EXP:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR CDD; cd15809; SPRY_PRY_TRIM4; 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; IPR035829; PRY/SPRY_TRIM4.
DR InterPro; IPR003877; SPRY_dom.
DR InterPro; IPR000315; Znf_B-box.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00622; SPRY; 1.
DR Pfam; PF00643; zf-B_box; 1.
DR PRINTS; PR01407; BUTYPHLNCDUF.
DR SMART; SM00336; BBOX; 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 Alternative splicing; Coiled coil; Cytoplasm; Immunity; Innate immunity;
KW Metal-binding; Reference proteome; Transferase; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..500
FT /note="E3 ubiquitin-protein ligase TRIM4"
FT /id="PRO_0000056200"
FT DOMAIN 288..500
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 12..53
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 82..123
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT COILED 212..253
FT /evidence="ECO:0000255"
FT BINDING 87
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 90
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 109
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT VAR_SEQ 132..157
FT /note="Missing (in isoform Beta and isoform Gamma)"
FT /evidence="ECO:0000303|PubMed:11331580,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_010197"
FT VAR_SEQ 307..320
FT /note="VAVNLAEDTAHPKL -> ATKIKTQKQNRHNM (in isoform Gamma)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_010198"
FT VAR_SEQ 321..500
FT /note="Missing (in isoform Gamma)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_010199"
FT VARIANT 367
FT /note="P -> S (in dbSNP:rs35432946)"
FT /id="VAR_046715"
FT VARIANT 474
FT /note="S -> C (in dbSNP:rs33998596)"
FT /id="VAR_046716"
FT MUTAGEN 27
FT /note="C->S: Abolishes ligase activity."
FT /evidence="ECO:0000269|PubMed:24755855"
FT CONFLICT 154
FT /note="F -> S (in Ref. 1; AAG53477)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 57461 MW; 427D7F3DBF53A72C CRC64;
MEAEDIQEEL TCPICLDYFQ DPVSIECGHN FCRGCLHRNW APGGGPFPCP ECRHPSAPAA
LRPNWALARL TEKTQRRRLG PVPPGLCGRH WEPLRLFCED DQRPVCLVCR ESQEHQTHAM
APIDEAFESY RTGNFDIHVD EWKRRLIRLL LYHFKQEEKL LKSQRNLVAK MKKVMHLQDV
EVKNATQWKD KIKSQRMRIS TEFSKLHNFL VEEEDLFLQR LNKEEEETKK KLNENTLKLN
QTIASLKKLI LEVGEKSQAP TLELLQNPKE VLTRSEIQDV NYSLEAVKVK TVCQIPLMKE
MLKRFQVAVN LAEDTAHPKL VFSQEGRYVK NTASASSWPV FSSAWNYFAG WRNPQKTAFV
ERFQHLPCVL GKNVFTSGKH YWEVESRDSL EVAVGVCRED VMGITDRSKM SPDVGIWAIY
WSAAGYWPLI GFPGTPTQQE PALHRVGVYL DRGTGNVSFY SAVDGVHLHT FSCSSVSRLR
PFFWLSPLAS LVIPPVTDRK
