TRI38_HUMAN
ID TRI38_HUMAN Reviewed; 465 AA.
AC O00635; B2R862;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM38 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000305|PubMed:23056470};
DE AltName: Full=RING finger protein 15;
DE AltName: Full=Tripartite motif-containing protein 38 {ECO:0000305};
DE AltName: Full=Zinc finger protein RoRet {ECO:0000303|PubMed:9149941};
GN Name=TRIM38 {ECO:0000303|PubMed:23056470, ECO:0000312|HGNC:HGNC:10059};
GN Synonyms=RNF15, RORET {ECO:0000303|PubMed:9149941};
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 [GENOMIC DNA / MRNA].
RX PubMed=9149941; DOI=10.1101/gr.7.5.441;
RA Ruddy D.A., Kronmal G.S., Lee V.K., Mintier G.A., Quintana L.,
RA Domingo R. Jr., Meyer N.C., Irrinki A., McClelland E.E., Fullan A.,
RA Mapa F.A., Moore T., Thomas W., Loeb D.B., Harmon C., Tsuchihashi Z.,
RA Wolff R.K., Schatzman R.C., Feder J.N.;
RT "A 1.1-Mb transcript map of the hereditary hemochromatosis locus.";
RL Genome Res. 7:441-456(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=23056470; DOI=10.1371/journal.pone.0046825;
RA Xue Q., Zhou Z., Lei X., Liu X., He B., Wang J., Hung T.;
RT "TRIM38 negatively regulates TLR3-mediated IFN-beta signaling by targeting
RT TRIF for degradation.";
RL PLoS ONE 7:E46825-E46825(2012).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
RP FUNCTION, AND INTERACTION WITH TAB2 AND TAB3.
RX PubMed=24434549; DOI=10.1073/pnas.1318227111;
RA Hu M.M., Yang Q., Zhang J., Liu S.M., Zhang Y., Lin H., Huang Z.F.,
RA Wang Y.Y., Zhang X.D., Zhong B., Shu H.B.;
RT "TRIM38 inhibits TNFalpha- and IL-1beta-triggered NF-kappaB activation by
RT mediating lysosome-dependent degradation of TAB2/3.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:1509-1514(2014).
CC -!- FUNCTION: E3 ubiquitin-protein and E3 SUMO-protein ligase that acts as
CC a regulator of innate immunity (PubMed:23056470). Acts as a negative
CC regulator of type I interferon IFN-beta production by catalyzing 'Lys-
CC 48'-linked polyubiquitination of AZI2/NAP1, leading to its degradation
CC (By similarity). Mediates 'Lys-48'-linked polyubiquitination and
CC proteasomal degradation of the critical TLR adapter TICAM1, inhibiting
CC TLR3-mediated type I interferon signaling (PubMed:23056470). Acts as
CC positive regulator of the cGAS-STING pathway by acting as a E3 SUMO-
CC protein ligase: mediates sumoylation of CGAS and STING, preventing
CC their degradation and thereby activating the innate immune response to
CC DNA virus (By similarity). Also acts as a negative regulator of NF-
CC kappa-B signaling independently of its E3 protein ligase activity by
CC promoting lysosome-dependent degradation of TAB2 and TAB3 adapters
CC (PubMed:24434549). {ECO:0000250|UniProtKB:Q5SZ99,
CC ECO:0000269|PubMed:23056470, ECO:0000269|PubMed:24434549}.
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:0000305|PubMed:23056470};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:23056470}.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC {ECO:0000250|UniProtKB:Q5SZ99}.
CC -!- SUBUNIT: Interacts (via B30.2/SPRY domain) with TAB2 and TAB3.
CC {ECO:0000250|UniProtKB:Q5SZ99}.
CC -!- INTERACTION:
CC O00635; P54253: ATXN1; NbExp=5; IntAct=EBI-2130415, EBI-930964;
CC O00635; Q13895: BYSL; NbExp=3; IntAct=EBI-2130415, EBI-358049;
CC O00635; Q53SE7: FLJ13057; NbExp=3; IntAct=EBI-2130415, EBI-10172181;
CC O00635; Q6FG85: GC20; NbExp=3; IntAct=EBI-2130415, EBI-10249571;
CC O00635; Q9H8Y8: GORASP2; NbExp=6; IntAct=EBI-2130415, EBI-739467;
CC O00635; P34931: HSPA1L; NbExp=3; IntAct=EBI-2130415, EBI-354912;
CC O00635; P54652: HSPA2; NbExp=4; IntAct=EBI-2130415, EBI-356991;
CC O00635; P11142: HSPA8; NbExp=6; IntAct=EBI-2130415, EBI-351896;
CC O00635; Q8N3F0: MTURN; NbExp=3; IntAct=EBI-2130415, EBI-11980301;
CC O00635; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-2130415, EBI-473160;
CC O00635; P25789: PSMA4; NbExp=3; IntAct=EBI-2130415, EBI-359310;
CC O00635; P40937: RFC5; NbExp=8; IntAct=EBI-2130415, EBI-712376;
CC O00635; P78317: RNF4; NbExp=3; IntAct=EBI-2130415, EBI-2340927;
CC O00635; O00560: SDCBP; NbExp=3; IntAct=EBI-2130415, EBI-727004;
CC O00635; P61764: STXBP1; NbExp=9; IntAct=EBI-2130415, EBI-960169;
CC O00635; Q15560: TCEA2; NbExp=3; IntAct=EBI-2130415, EBI-710310;
CC O00635; Q9UJ04: TSPYL4; NbExp=6; IntAct=EBI-2130415, EBI-308511;
CC O00635; Q7KZS0: UBE2I; NbExp=6; IntAct=EBI-2130415, EBI-10180829;
CC O00635; Q96H86: ZNF764; NbExp=3; IntAct=EBI-2130415, EBI-745775;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q5SZ99}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:9149941}.
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DR EMBL; U91328; AAB82084.1; -; Genomic_DNA.
DR EMBL; U90547; AAB53425.1; -; mRNA.
DR EMBL; AK313248; BAG36059.1; -; mRNA.
DR EMBL; BC026930; AAH26930.1; -; mRNA.
DR CCDS; CCDS4568.1; -.
DR RefSeq; NP_006346.1; NM_006355.4.
DR RefSeq; XP_005248856.1; XM_005248799.4.
DR RefSeq; XP_005248857.1; XM_005248800.4.
DR AlphaFoldDB; O00635; -.
DR SMR; O00635; -.
DR BioGRID; 115738; 49.
DR IntAct; O00635; 23.
DR MINT; O00635; -.
DR STRING; 9606.ENSP00000349596; -.
DR GlyGen; O00635; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O00635; -.
DR PhosphoSitePlus; O00635; -.
DR BioMuta; TRIM38; -.
DR EPD; O00635; -.
DR jPOST; O00635; -.
DR MassIVE; O00635; -.
DR MaxQB; O00635; -.
DR PaxDb; O00635; -.
DR PeptideAtlas; O00635; -.
DR PRIDE; O00635; -.
DR ProteomicsDB; 48005; -.
DR Antibodypedia; 10788; 516 antibodies from 30 providers.
DR DNASU; 10475; -.
DR Ensembl; ENST00000357085.5; ENSP00000349596.2; ENSG00000112343.11.
DR GeneID; 10475; -.
DR KEGG; hsa:10475; -.
DR MANE-Select; ENST00000357085.5; ENSP00000349596.2; NM_006355.5; NP_006346.1.
DR UCSC; uc003nfm.5; human.
DR CTD; 10475; -.
DR DisGeNET; 10475; -.
DR GeneCards; TRIM38; -.
DR HGNC; HGNC:10059; TRIM38.
DR HPA; ENSG00000112343; Low tissue specificity.
DR neXtProt; NX_O00635; -.
DR OpenTargets; ENSG00000112343; -.
DR PharmGKB; PA35532; -.
DR VEuPathDB; HostDB:ENSG00000112343; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000160468; -.
DR HOGENOM; CLU_013137_0_3_1; -.
DR InParanoid; O00635; -.
DR OMA; RPYFRVY; -.
DR OrthoDB; 423686at2759; -.
DR PhylomeDB; O00635; -.
DR TreeFam; TF342569; -.
DR PathwayCommons; O00635; -.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR SignaLink; O00635; -.
DR UniPathway; UPA00143; -.
DR UniPathway; UPA00886; -.
DR BioGRID-ORCS; 10475; 16 hits in 1119 CRISPR screens.
DR ChiTaRS; TRIM38; human.
DR GenomeRNAi; 10475; -.
DR Pharos; O00635; Tbio.
DR PRO; PR:O00635; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O00635; protein.
DR Bgee; ENSG00000112343; Expressed in cardia of stomach and 204 other tissues.
DR ExpressionAtlas; O00635; baseline and differential.
DR Genevisible; O00635; HS.
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; IDA:ARUK-UCL.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS: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; IEA:Ensembl.
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; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0046598; P:positive regulation of viral entry into host cell; IDA:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; IEA:Ensembl.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IEA:Ensembl.
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; IEA:Ensembl.
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; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..465
FT /note="E3 ubiquitin-protein ligase TRIM38"
FT /id="PRO_0000056256"
FT DOMAIN 274..465
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 16..63
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 88..129
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 96
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 BINDING 121
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 421
FT /note="G -> R (in dbSNP:rs10317)"
FT /id="VAR_013513"
FT CONFLICT 23
FT /note="M -> I (in Ref. 3; AAH26930)"
FT /evidence="ECO:0000305"
FT CONFLICT 411
FT /note="L -> P (in Ref. 2; BAG36059)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 465 AA; 53416 MW; 30A884051A2DA058 CRC64;
MASTTSTKKM MEEATCSICL SLMTNPVSIN CGHSYCHLCI TDFFKNPSQK QLRQETFCCP
QCRAPFHMDS LRPNKQLGSL IEALKETDQE MSCEEHGEQF HLFCEDEGQL ICWRCERAPQ
HKGHTTALVE DVCQGYKEKL QKAVTKLKQL EDRCTEQKLS TAMRITKWKE KVQIQRQKIR
SDFKNLQCFL HEEEKSYLWR LEKEEQQTLS RLRDYEAGLG LKSNELKSHI LELEEKCQGS
AQKLLQNVND TLSRSWAVKL ETSEAVSLEL HTMCNVSKLY FDVKKMLRSH QVSVTLDPDT
AHHELILSED RRQVTRGYTQ ENQDTSSRRF TAFPCVLGCE GFTSGRRYFE VDVGEGTGWD
LGVCMENVQR GTGMKQEPQS GFWTLRLCKK KGYVALTSPP TSLHLHEQPL LVGIFLDYEA
GVVSFYNGNT GCHIFTFPKA SFSDTLRPYF QVYQYSPLFL PPPGD
