TRAF7_HUMAN
ID TRAF7_HUMAN Reviewed; 670 AA.
AC Q6Q0C0; Q9H073;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=E3 ubiquitin-protein ligase TRAF7;
DE EC=2.3.2.27;
DE AltName: Full=RING finger and WD repeat-containing protein 1;
DE AltName: Full=RING finger protein 119;
DE AltName: Full=RING-type E3 ubiquitin transferase TRAF7 {ECO:0000305};
DE AltName: Full=TNF receptor-associated factor 7;
GN Name=TRAF7; Synonyms=RFWD1, RNF119;
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] {ECO:0000305, ECO:0000312|EMBL:AAS68363.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP ALTERNATIVE SPLICING, AND INTERACTION WITH MAP3K3.
RX PubMed=15001576; DOI=10.1074/jbc.c400063200;
RA Xu L.-G., Li L.-Y., Shu H.-B.;
RT "TRAF7 potentiates MEKK3-induced AP1 and CHOP activation and induces
RT apoptosis.";
RL J. Biol. Chem. 279:17278-17282(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3] {ECO:0000305}
RP FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, HOMODIMERIZATION, AND
RP INTERACTION WITH MAP3K3.
RX PubMed=14743216; DOI=10.1038/ncb1086;
RA Bouwmeester T., Bauch A., Ruffner H., Angrand P.-O., Bergamini G.,
RA Croughton K., Cruciat C., Eberhard D., Gagneur J., Ghidelli S., Hopf C.,
RA Huhse B., Mangano R., Michon A.-M., Schirle M., Schlegl J., Schwab M.,
RA Stein M.A., Bauer A., Casari G., Drewes G., Gavin A.-C., Jackson D.B.,
RA Joberty G., Neubauer G., Rick J., Kuster B., Superti-Furga G.;
RT "A physical and functional map of the human TNF-alpha/NF-kappa B signal
RT transduction pathway.";
RL Nat. Cell Biol. 6:97-105(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88 AND SER-91, AND
RP IDENTIFICATION BY 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61, 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 [6]
RP FUNCTION, INVOLVEMENT IN CAFDADD, VARIANTS CAFDADD GLU-346; GLY-371;
RP ALA-601 AND GLN-655, AND CHARACTERIZATION OF VARIANTS CAFDADD GLU-346;
RP GLY-371; ALA-601 AND GLN-655.
RX PubMed=29961569; DOI=10.1016/j.ajhg.2018.06.005;
RG Undiagnosed Diseases Network;
RA Tokita M.J., Chen C.A., Chitayat D., Macnamara E., Rosenfeld J.A.,
RA Hanchard N., Lewis A.M., Brown C.W., Marom R., Shao Y., Novacic D.,
RA Wolfe L., Wahl C., Tifft C.J., Toro C., Bernstein J.A., Hale C.L.,
RA Silver J., Hudgins L., Ananth A., Hanson-Kahn A., Shuster S.,
RA Magoulas P.L., Patel V.N., Zhu W., Chen S.M., Jiang Y., Liu P., Eng C.M.,
RA Batkovskyte D., di Ronza A., Sardiello M., Lee B.H., Schaaf C.P., Yang Y.,
RA Wang X.;
RT "De novo missense variants in TRAF7 cause developmental delay, congenital
RT anomalies, and dysmorphic features.";
RL Am. J. Hum. Genet. 103:154-162(2018).
CC -!- FUNCTION: E3 ubiquitin ligase capable of auto-ubiquitination, following
CC phosphorylation by MAP3K3. Potentiates MAP3K3-mediated activation of
CC the NF-kappa-B, JUN/AP1 and DDIT3 transcriptional regulators
CC (PubMed:14743216). Induces apoptosis when overexpressed
CC (PubMed:15001576). Plays a role in the phosphorylation of MAPK1 and/or
CC MAPK3, probably via its interaction with MAP3K3.
CC {ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:15001576,
CC ECO:0000269|PubMed:29961569}.
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: Homodimer. Interacts with MAP3K3 and promotes the kinase
CC activity of this enzyme. {ECO:0000269|PubMed:14743216,
CC ECO:0000269|PubMed:15001576}.
CC -!- INTERACTION:
CC Q6Q0C0; Q99759: MAP3K3; NbExp=3; IntAct=EBI-307556, EBI-307281;
CC Q6Q0C0; Q9ERK0: Ripk4; Xeno; NbExp=2; IntAct=EBI-307556, EBI-6116422;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle
CC {ECO:0000269|PubMed:14743216}. Note=Colocalizes with MAP3K3 to vesicle-
CC like structures throughout the cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:15001576};
CC IsoId=Q6Q0C0-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15001576};
CC IsoId=Q6Q0C0-2; Sequence=VSP_051607;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with high levels in skeletal
CC muscle, heart, colon, spleen, kidney, liver and placenta.
CC {ECO:0000269|PubMed:15001576}.
CC -!- PTM: Phosphorylated by MAP3K3. {ECO:0000269|PubMed:14743216}.
CC -!- PTM: Ubiquitinates itself upon phosphorylation.
CC -!- DISEASE: Cardiac, facial, and digital anomalies with developmental
CC delay (CAFDADD) [MIM:618164]: An autosomal dominant disorder
CC characterized by delayed motor and speech development, developmental
CC regression, congenital heart defects, limb and digital anomalies, and
CC dysmorphic features. Cardiac features include pulmonary stenosis,
CC patent ductus arteriosus, aortic coarctation, valvular defects,
CC hypoplastic left heart, double outlet right ventricle, and conduction
CC abnormalities. Dysmorphic facial features include multiple hair whorls
CC or hairline abnormalities, ptosis, epicanthal folds, and low-set or
CC dysplastic ears. {ECO:0000269|PubMed:29961569}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the WD repeat TRAF7 family. {ECO:0000305}.
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DR EMBL; AY569455; AAS68363.1; -; mRNA.
DR EMBL; AL136921; CAB66855.1; -; mRNA.
DR CCDS; CCDS10461.1; -. [Q6Q0C0-1]
DR RefSeq; NP_115647.2; NM_032271.2. [Q6Q0C0-1]
DR AlphaFoldDB; Q6Q0C0; -.
DR SMR; Q6Q0C0; -.
DR BioGRID; 123964; 114.
DR CORUM; Q6Q0C0; -.
DR IntAct; Q6Q0C0; 47.
DR MINT; Q6Q0C0; -.
DR STRING; 9606.ENSP00000318944; -.
DR iPTMnet; Q6Q0C0; -.
DR PhosphoSitePlus; Q6Q0C0; -.
DR BioMuta; TRAF7; -.
DR DMDM; 54036486; -.
DR EPD; Q6Q0C0; -.
DR jPOST; Q6Q0C0; -.
DR MassIVE; Q6Q0C0; -.
DR MaxQB; Q6Q0C0; -.
DR PaxDb; Q6Q0C0; -.
DR PeptideAtlas; Q6Q0C0; -.
DR PRIDE; Q6Q0C0; -.
DR ProteomicsDB; 67263; -. [Q6Q0C0-1]
DR ProteomicsDB; 67264; -. [Q6Q0C0-2]
DR Antibodypedia; 23591; 186 antibodies from 29 providers.
DR DNASU; 84231; -.
DR Ensembl; ENST00000326181.11; ENSP00000318944.6; ENSG00000131653.13. [Q6Q0C0-1]
DR GeneID; 84231; -.
DR KEGG; hsa:84231; -.
DR MANE-Select; ENST00000326181.11; ENSP00000318944.6; NM_032271.3; NP_115647.2.
DR UCSC; uc002cow.4; human. [Q6Q0C0-1]
DR CTD; 84231; -.
DR DisGeNET; 84231; -.
DR GeneCards; TRAF7; -.
DR HGNC; HGNC:20456; TRAF7.
DR HPA; ENSG00000131653; Low tissue specificity.
DR MalaCards; TRAF7; -.
DR MIM; 606692; gene.
DR MIM; 618164; phenotype.
DR neXtProt; NX_Q6Q0C0; -.
DR OpenTargets; ENSG00000131653; -.
DR Orphanet; 2495; Meningioma.
DR Orphanet; 592570; TRAF7-associated heart defect-digital anomalies-facial dysmorphism-motor and speech delay syndrome.
DR PharmGKB; PA134917323; -.
DR VEuPathDB; HostDB:ENSG00000131653; -.
DR eggNOG; KOG0274; Eukaryota.
DR eggNOG; KOG0297; Eukaryota.
DR GeneTree; ENSGT00940000157022; -.
DR HOGENOM; CLU_026971_0_0_1; -.
DR InParanoid; Q6Q0C0; -.
DR OMA; NHHILCG; -.
DR PhylomeDB; Q6Q0C0; -.
DR TreeFam; TF328643; -.
DR PathwayCommons; Q6Q0C0; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q6Q0C0; -.
DR SIGNOR; Q6Q0C0; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 84231; 29 hits in 1113 CRISPR screens.
DR GenomeRNAi; 84231; -.
DR Pharos; Q6Q0C0; Tbio.
DR PRO; PR:Q6Q0C0; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q6Q0C0; protein.
DR Bgee; ENSG00000131653; Expressed in stromal cell of endometrium and 161 other tissues.
DR ExpressionAtlas; Q6Q0C0; baseline and differential.
DR Genevisible; Q6Q0C0; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IDA:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0000027; P:ribosomal large subunit assembly; IBA:GO_Central.
DR Gene3D; 2.130.10.10; -; 2.
DR Gene3D; 3.30.40.10; -; 2.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR027370; Znf-RING_LisH.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR InterPro; IPR001293; Znf_TRAF.
DR Pfam; PF00400; WD40; 4.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00184; RING; 1.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 5.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS50145; ZF_TRAF; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Cytoplasmic vesicle; Disease variant;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; WD repeat; Zinc; Zinc-finger.
FT CHAIN 1..670
FT /note="E3 ubiquitin-protein ligase TRAF7"
FT /id="PRO_0000051296"
FT REPEAT 394..433
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 437..474
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 477..513
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 515..554
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 557..594
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REPEAT 597..638
FT /note="WD 6"
FT /evidence="ECO:0000255"
FT REPEAT 641..669
FT /note="WD 7"
FT /evidence="ECO:0000255"
FT ZN_FING 131..165
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 222..276
FT /note="TRAF-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 49..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..70
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..97
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 1..76
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11230166,
FT ECO:0000303|PubMed:15001576"
FT /id="VSP_051607"
FT VARIANT 346
FT /note="K -> E (in CAFDADD; no significant effect on
FT phosphorylation of MAPK1 and/or MAPK3; dbSNP:rs1567252467)"
FT /evidence="ECO:0000269|PubMed:29961569"
FT /id="VAR_081685"
FT VARIANT 371
FT /note="R -> G (in CAFDADD; decreased phosphorylation of
FT MAPK1 and/or MAPK3; dbSNP:rs1567252659)"
FT /evidence="ECO:0000269|PubMed:29961569"
FT /id="VAR_081686"
FT VARIANT 601
FT /note="T -> A (in CAFDADD; decreased phosphorylation of
FT MAPK1 and/or MAPK3; dbSNP:rs1567254067)"
FT /evidence="ECO:0000269|PubMed:29961569"
FT /id="VAR_081687"
FT VARIANT 655
FT /note="R -> Q (in CAFDADD; decreased phosphorylation of
FT MAPK1 and/or MAPK3; dbSNP:rs1331463984)"
FT /evidence="ECO:0000269|PubMed:29961569"
FT /id="VAR_081688"
SQ SEQUENCE 670 AA; 74609 MW; 5624045D674849C6 CRC64;
MSSGKSARYN RFSGGPSNLP TPDVTTGTRM ETTFGPAFSA VTTITKADGT STYKQHCRTP
SSSSTLAYSP RDEEDSMPPI STPRRSDSAI SVRSLHSESS MSLRSTFSLP EEEEEPEPLV
FAEQPSVKLC CQLCCSVFKD PVITTCGHTF CRRCALKSEK CPVDNVKLTV VVNNIAVAEQ
IGELFIHCRH GCRVAGSGKP PIFEVDPRGC PFTIKLSARK DHEGSCDYRP VRCPNNPSCP
PLLRMNLEAH LKECEHIKCP HSKYGCTFIG NQDTYETHLE TCRFEGLKEF LQQTDDRFHE
MHVALAQKDQ EIAFLRSMLG KLSEKIDQLE KSLELKFDVL DENQSKLSED LMEFRRDASM
LNDELSHINA RLNMGILGSY DPQQIFKCKG TFVGHQGPVW CLCVYSMGDL LFSGSSDKTI
KVWDTCTTYK CQKTLEGHDG IVLALCIQGC KLYSGSADCT IIVWDIQNLQ KVNTIRAHDN
PVCTLVSSHN VLFSGSLKAI KVWDIVGTEL KLKKELTGLN HWVRALVAAQ SYLYSGSYQT
IKIWDIRTLD CIHVLQTSGG SVYSIAVTNH HIVCGTYENL IHVWDIESKE QVRTLTGHVG
TVYALAVIST PDQTKVFSAS YDRSLRVWSM DNMICTQTLL RHQGSVTALA VSRGRLFSGA
VDSTVKVWTC
