TRI38_MOUSE
ID TRI38_MOUSE Reviewed; 471 AA.
AC Q5SZ99; B9EKD3;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM38 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:22539786, ECO:0000269|PubMed:26392463};
DE AltName: Full=E3 SUMO-protein ligase TRIM38 {ECO:0000305};
DE EC=2.3.2.- {ECO:0000269|PubMed:27637147};
DE AltName: Full=Tripartite motif-containing protein 38 {ECO:0000305};
GN Name=Trim38 {ECO:0000303|PubMed:22539786, ECO:0000312|MGI:MGI:2684869};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, INTERACTION
RP WITH TAB2 AND TAB3, AND MUTAGENESIS OF CYS-16.
RX PubMed=22539786; DOI=10.4049/jimmunol.1103506;
RA Zhao W., Wang L., Zhang M., Wang P., Yuan C., Qi J., Meng H., Gao C.;
RT "Tripartite motif-containing protein 38 negatively regulates TLR3/4- and
RT RIG-I-mediated IFN-beta production and antiviral response by targeting
RT NAP1.";
RL J. Immunol. 188:5311-5318(2012).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF CYS-31.
RX PubMed=26392463; DOI=10.4049/jimmunol.1500859;
RA Hu M.M., Xie X.Q., Yang Q., Liao C.Y., Ye W., Lin H., Shu H.B.;
RT "TRIM38 negatively regulates TLR3/4-mediated innate immune and inflammatory
RT responses by two sequential and distinct mechanisms.";
RL J. Immunol. 195:4415-4425(2015).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF CYS-31.
RX PubMed=27637147; DOI=10.1016/j.immuni.2016.08.014;
RA Hu M.M., Yang Q., Xie X.Q., Liao C.Y., Lin H., Liu T.T., Yin L., Shu H.B.;
RT "Sumoylation promotes the stability of the DNA sensor cGAS and the adaptor
RT STING to regulate the kinetics of response to DNA virus.";
RL Immunity 45:555-569(2016).
CC -!- FUNCTION: E3 ubiquitin-protein and E3 SUMO-protein ligase that acts as
CC a regulator of innate immunity (PubMed:22539786, PubMed:26392463,
CC PubMed:27637147). Acts as a negative regulator of type I interferon
CC IFN-beta production by catalyzing 'Lys-48'-linked polyubiquitination of
CC AZI2/NAP1, leading to its degradation (PubMed:22539786). Mediates 'Lys-
CC 48'-linked polyubiquitination and proteasomal degradation of the
CC critical TLR adapter TICAM1, inhibiting TLR3-mediated type I interferon
CC signaling (PubMed:26392463). Acts as positive regulator of the cGAS-
CC STING pathway by acting as a E3 SUMO-protein ligase: mediates
CC sumoylation of CGAS and STING, preventing their degradation and thereby
CC activating the innate immune response to DNA virus (PubMed:27637147).
CC Also acts as a negative regulator of NF-kappa-B signaling independently
CC of its E3 protein ligase activity by promoting lysosome-dependent
CC degradation of TAB2 and TAB3 adapters (By similarity).
CC {ECO:0000250|UniProtKB:O00635, ECO:0000269|PubMed:22539786,
CC ECO:0000269|PubMed:26392463, ECO:0000269|PubMed:27637147}.
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; Evidence={ECO:0000269|PubMed:22539786,
CC ECO:0000269|PubMed:26392463};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:22539786, ECO:0000269|PubMed:26392463}.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC {ECO:0000269|PubMed:27637147}.
CC -!- SUBUNIT: Interacts (via B30.2/SPRY domain) with TAB2 and TAB3.
CC {ECO:0000269|PubMed:22539786}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22539786}.
CC -!- DISRUPTION PHENOTYPE: Mice are more susceptible to death triggered by
CC polyinosinic:polycytidylic acid, LPS and S.typhimurium
CC (PubMed:26392463). Increased TLR3/4-mediated cytokine induction
CC (PubMed:26392463). {ECO:0000269|PubMed:26392463}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL590388; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC150836; AAI50837.1; -; mRNA.
DR CCDS; CCDS26370.1; -.
DR RefSeq; NP_001025106.1; NM_001029935.2.
DR RefSeq; XP_006516700.1; XM_006516637.2.
DR RefSeq; XP_011242605.1; XM_011244303.1.
DR AlphaFoldDB; Q5SZ99; -.
DR SMR; Q5SZ99; -.
DR STRING; 10090.ENSMUSP00000073709; -.
DR PhosphoSitePlus; Q5SZ99; -.
DR MaxQB; Q5SZ99; -.
DR PaxDb; Q5SZ99; -.
DR PRIDE; Q5SZ99; -.
DR ProteomicsDB; 339470; -.
DR Antibodypedia; 10788; 516 antibodies from 30 providers.
DR DNASU; 214158; -.
DR Ensembl; ENSMUST00000074067; ENSMUSP00000073709; ENSMUSG00000064140.
DR Ensembl; ENSMUST00000226039; ENSMUSP00000153240; ENSMUSG00000064140.
DR GeneID; 214158; -.
DR KEGG; mmu:214158; -.
DR UCSC; uc007pva.2; mouse.
DR CTD; 10475; -.
DR MGI; MGI:2684869; Trim38.
DR VEuPathDB; HostDB:ENSMUSG00000064140; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000160468; -.
DR HOGENOM; CLU_013137_0_3_1; -.
DR InParanoid; Q5SZ99; -.
DR OMA; RPYFRVY; -.
DR OrthoDB; 423686at2759; -.
DR PhylomeDB; Q5SZ99; -.
DR TreeFam; TF342569; -.
DR UniPathway; UPA00143; -.
DR UniPathway; UPA00886; -.
DR BioGRID-ORCS; 214158; 4 hits in 72 CRISPR screens.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q5SZ99; protein.
DR Bgee; ENSMUSG00000064140; Expressed in morula and 16 other tissues.
DR ExpressionAtlas; Q5SZ99; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
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:0003713; F:transcription coactivator activity; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0050687; P:negative regulation of defense response to virus; IMP:MGI.
DR GO; GO:0010508; P:positive regulation of autophagy; IBA:GO_Central.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0046598; P:positive regulation of viral entry into host cell; ISO:MGI.
DR GO; GO:0045070; P:positive regulation of viral genome replication; IDA:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0016925; P:protein sumoylation; IEA:UniProtKB-UniPathway.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0032648; P:regulation of interferon-beta production; IDA:MGI.
DR GO; GO:0032880; P:regulation of protein localization; IBA:GO_Central.
DR GO; GO:0046596; P:regulation of viral entry into host cell; IBA:GO_Central.
DR CDD; cd15815; SPRY_PRY_TRIM38; 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; IPR035790; SPRY/PRY_TRIM38.
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; PF13765; PRY; 1.
DR Pfam; PF00622; SPRY; 1.
DR Pfam; PF00643; zf-B_box; 1.
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 Cytoplasm; Immunity; Innate immunity; Metal-binding; Reference proteome;
KW Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..471
FT /note="E3 ubiquitin-protein ligase TRIM38"
FT /id="PRO_0000454476"
FT DOMAIN 276..471
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 16..62
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 90..131
FT /note="B box-type"
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 98
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 117
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 123
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT MUTAGEN 16
FT /note="C->A: Abolished E3 ubiquitin-protein activity and
FT ability to inhibit type I interferon IFN-beta production."
FT /evidence="ECO:0000269|PubMed:22539786"
FT MUTAGEN 31
FT /note="C->S: Abolished E3 ubiquitin-protein activity and
FT ability to ubiquitinate TICAM1. Abolished E3 SUMO-protein
FT activity and ability to sumoylate CGAS."
FT /evidence="ECO:0000269|PubMed:26392463,
FT ECO:0000269|PubMed:27637147"
FT CONFLICT 7
FT /note="T -> M (in Ref. 2; AAI50837)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 471 AA; 54430 MW; 9C4BE6BACFAD6540 CRC64;
MGSDFSTVKI RKVTSCSICK AMMSHPVSIN CGHSYCKSCI QSYYCNVSPK TGWKMLGCPL
CSSPFSLENL RPNKELETII DMIKGMEEQD QDMVCEEHEE KFNRFCEDDG QLLCWRCYWE
DRHKGHTLAH VKDVYQNYKE KLQNTMTKLR ELQENHEVQI HFITHQINAW KDAVEDRRQT
IKSNFKNLQS FLQEEEKFYL WRLENEEKEM LVQLEGSEAN LQQTFERAQC QIQELEAKCQ
GSAQKLLQDV KNTLSRCEAM KRNPLKADPL KVHTKCNVSE LYFDVKTILR RHQVSVILDP
STAHLDLALT KGGRLVTYKR CPRDLQARSS AKRFYGLPCV LGCEGFTSGR YYFEVSVENA
TSWDLGVCVE NVHRGFNMKK EPESGFWTIK MSEEDGLEAL TSTPTPPLHL IEKPQILGVF
LDYEAGAVSF YSVTTGSHIF TFPKASFQDT LRPFFQVYQY SPLFLPAINN Q
