ID DTX4_HUMAN Reviewed; 619 AA.
AC Q9Y2E6; Q0VF38;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 2.
DT 27-MAR-2024, entry version 162.
DE RecName: Full=E3 ubiquitin-protein ligase DTX4;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q61010};
DE AltName: Full=Protein deltex-4;
DE Short=Deltex4;
DE AltName: Full=RING finger protein 155;
DE AltName: Full=RING-type E3 ubiquitin transferase DTX4 {ECO:0000305};
GN Name=DTX4; Synonyms=KIAA0937, RNF155;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 IDENTIFICATION.
RX PubMed=15684394; DOI=10.1128/mcb.25.4.1437-1445.2005;
RA Storck S., Delbos F., Stadler N., Thirion-Delalande C., Bernex F.,
RA Verthuy C., Ferrier P., Weill J.-C., Reynaud C.-A.;
RT "Normal immune system development in mice lacking the Deltex-1 RING finger
RT domain.";
RL Mol. Cell. Biol. 25:1437-1445(2005).
RN [4]
RP FUNCTION AS E3 LIGASE, AND INTERACTION WITH NLRP4.
RX PubMed=22388039; DOI=10.1038/ni.2239;
RA Cui J., Li Y., Zhu L., Liu D., Songyang Z., Wang H.Y., Wang R.F.;
RT "NLRP4 negatively regulates type I interferon signaling by targeting the
RT kinase TBK1 for degradation via the ubiquitin ligase DTX4.";
RL Nat. Immunol. 13:387-395(2012).
CC -!- FUNCTION: Regulator of Notch signaling, a signaling pathway involved in
CC cell-cell communications that regulates a broad spectrum of cell-fate
CC determinations (By similarity). Functions as a ubiquitin ligase protein
CC in vivo, mediating 'Lys48'-linked polyubiquitination and promoting
CC degradation of TBK1, targeting to TBK1 requires interaction with NLRP4.
CC {ECO:0000250, ECO:0000269|PubMed:22388039}.
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:0000250|UniProtKB:Q61010};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with NLRP4. {ECO:0000269|PubMed:22388039}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y2E6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y2E6-2; Sequence=VSP_023784;
CC -!- DOMAIN: The WWE domains are thought to mediate some protein-protein
CC interaction, and are frequently found in ubiquitin ligases.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the Deltex family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA76781.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB023154; BAA76781.1; ALT_INIT; mRNA.
DR EMBL; BC119011; AAI19012.1; -; mRNA.
DR EMBL; BC122861; AAI22862.1; -; mRNA.
DR CCDS; CCDS44612.1; -. [Q9Y2E6-1]
DR CCDS; CCDS76408.1; -. [Q9Y2E6-2]
DR RefSeq; NP_001287656.1; NM_001300727.1. [Q9Y2E6-2]
DR RefSeq; NP_055992.1; NM_015177.1. [Q9Y2E6-1]
DR RefSeq; XP_006718546.1; XM_006718483.3.
DR AlphaFoldDB; Q9Y2E6; -.
DR SMR; Q9Y2E6; -.
DR BioGRID; 116827; 21.
DR IntAct; Q9Y2E6; 2.
DR STRING; 9606.ENSP00000227451; -.
DR GlyGen; Q9Y2E6; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q9Y2E6; -.
DR PhosphoSitePlus; Q9Y2E6; -.
DR BioMuta; DTX4; -.
DR DMDM; 134034097; -.
DR MassIVE; Q9Y2E6; -.
DR PaxDb; 9606-ENSP00000227451; -.
DR PeptideAtlas; Q9Y2E6; -.
DR ProteomicsDB; 85749; -. [Q9Y2E6-1]
DR ProteomicsDB; 85750; -. [Q9Y2E6-2]
DR Antibodypedia; 52744; 151 antibodies from 23 providers.
DR DNASU; 23220; -.
DR Ensembl; ENST00000227451.4; ENSP00000227451.3; ENSG00000110042.8. [Q9Y2E6-1]
DR Ensembl; ENST00000532982.5; ENSP00000434055.1; ENSG00000110042.8. [Q9Y2E6-2]
DR GeneID; 23220; -.
DR KEGG; hsa:23220; -.
DR MANE-Select; ENST00000227451.4; ENSP00000227451.3; NM_015177.2; NP_055992.1.
DR UCSC; uc001nnr.3; human. [Q9Y2E6-1]
DR AGR; HGNC:29151; -.
DR DisGeNET; 23220; -.
DR GeneCards; DTX4; -.
DR HGNC; HGNC:29151; DTX4.
DR HPA; ENSG00000110042; Tissue enhanced (brain).
DR MIM; 616110; gene.
DR neXtProt; NX_Q9Y2E6; -.
DR OpenTargets; ENSG00000110042; -.
DR PharmGKB; PA134930720; -.
DR VEuPathDB; HostDB:ENSG00000110042; -.
DR eggNOG; ENOG502QQ9M; Eukaryota.
DR GeneTree; ENSGT00940000157122; -.
DR HOGENOM; CLU_030422_4_0_1; -.
DR InParanoid; Q9Y2E6; -.
DR OMA; PVPACTC; -.
DR OrthoDB; 5487971at2759; -.
DR PhylomeDB; Q9Y2E6; -.
DR TreeFam; TF325526; -.
DR PathwayCommons; Q9Y2E6; -.
DR Reactome; R-HSA-1606341; IRF3 mediated activation of type 1 IFN.
DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR Reactome; R-HSA-3134975; Regulation of innate immune responses to cytosolic DNA.
DR Reactome; R-HSA-3270619; IRF3-mediated induction of type I IFN.
DR SignaLink; Q9Y2E6; -.
DR SIGNOR; Q9Y2E6; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 23220; 18 hits in 1188 CRISPR screens.
DR ChiTaRS; DTX4; human.
DR GenomeRNAi; 23220; -.
DR Pharos; Q9Y2E6; Tbio.
DR PRO; PR:Q9Y2E6; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9Y2E6; Protein.
DR Bgee; ENSG00000110042; Expressed in inferior olivary complex and 193 other cell types or tissues.
DR Genevisible; Q9Y2E6; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProt.
DR GO; GO:0005737; C:cytoplasm; IC:UniProt.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProt.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0045824; P:negative regulation of innate immune response; IDA:UniProt.
DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IDA:UniProt.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProt.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProt.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0032479; P:regulation of type I interferon production; TAS:Reactome.
DR CDD; cd09633; Deltex_C; 1.
DR CDD; cd16671; RING-H2_DTX1_4; 1.
DR Gene3D; 3.30.390.130; -; 1.
DR Gene3D; 3.30.720.50; -; 2.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR InterPro; IPR039396; Deltex_C.
DR InterPro; IPR039399; Deltex_C_sf.
DR InterPro; IPR039398; Deltex_fam.
DR InterPro; IPR004170; WWE-dom.
DR InterPro; IPR018123; WWE-dom_subgr.
DR InterPro; IPR037197; WWE_dom_sf.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR12622; DELTEX-RELATED; 1.
DR PANTHER; PTHR12622:SF5; E3 UBIQUITIN-PROTEIN LIGASE DTX4; 1.
DR Pfam; PF18102; DTC; 1.
DR Pfam; PF02825; WWE; 2.
DR Pfam; PF00097; zf-C3HC4; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00678; WWE; 2.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR SUPFAM; SSF117839; WWE domain; 2.
DR PROSITE; PS50918; WWE; 2.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Metal-binding; Notch signaling pathway;
KW Reference proteome; Repeat; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..619
FT /note="E3 ubiquitin-protein ligase DTX4"
FT /id="PRO_0000280555"
FT DOMAIN 1..78
FT /note="WWE 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT DOMAIN 79..155
FT /note="WWE 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT ZN_FING 409..468
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 238..281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 358..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 256..281
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..106
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023784"
SQ SEQUENCE 619 AA; 67258 MW; 5C851845B42630BD CRC64;
MLLASAVVVW EWLNEHGRWR PYSPAVSHHI EAVVRAGPRA GGSVVLGQVD SRLAPYIIDL
QSMNQFRQDT GTLRPVRRNY YDPSSAPGKG VVWEWENDNG SWTPYDMEVG ITIQHAYEKQ
HPWIDLTSIG FSYVIDFNTM GQINRQTQRQ RRVRRRLDLI YPMVTGTLPK AQSWPVSPGP
ATSPPMSPCS CPQCVLVMSV KAAVVNGSTG PLQLPVTRKN MPPPGVVKLP PLPGSGAKPL
DSTGTIRGPL KTAPSQVIRR QASSMPTGTT MGSPASPPGP NSKTGRVALA TLNRTNLQRL
AIAQSRVLIA SGVPTVPVKN LNGSSPVNPA LAGITGILMS AAGLPVCLTR PPKLVLHPPP
VSKSEIKSIP GVSNTSRKTT KKQAKKGKTP EEVLKKYLQK VRHPPDEDCT ICMERLTAPS
GYKGPQPTVK PDLVGKLSRC GHVYHIYCLV AMYNNGNKDG SLQCPTCKTI YGVKTGTQPP
GKMEYHLIPH SLPGHPDCKT IRIIYSIPPG IQGPEHPNPG KSFSARGFPR HCYLPDSEKG
RKVLKLLLVA WDRRLIFAIG TSSTTGESDT VIWNEVHHKT EFGSNLTGHG YPDANYLDNV
LAELAAQGIS EDSTAQEKD
//
