DTX1_HUMAN
ID DTX1_HUMAN Reviewed; 620 AA.
AC Q86Y01; O60630; Q9BS04;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=E3 ubiquitin-protein ligase DTX1;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q61010};
DE AltName: Full=Protein deltex-1;
DE Short=Deltex1;
DE Short=hDTX1;
DE AltName: Full=RING-type E3 ubiquitin transferase DTX1 {ECO:0000305};
GN Name=DTX1;
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], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INTERACTION WITH NOTCH1.
RC TISSUE=Fetal brain;
RX PubMed=9590294; DOI=10.1038/ng0598-74;
RA Matsuno K., Eastman D., Mitsiades T., Quinn A.M., Carcanciu M.L.,
RA Ordentlich P., Kadesch T., Artavanis-Tsakonas S.;
RT "Human deltex is a conserved regulator of Notch signalling.";
RL Nat. Genet. 19:74-78(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
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.
RX PubMed=11869684; DOI=10.1016/s1074-7613(02)00271-6;
RA Izon D.J., Aster J.C., He Y., Weng A., Karnell F.G., Patriub V., Xu L.,
RA Bakkour S., Rodriguez C., Allman D., Pear W.S.;
RT "Deltex1 redirects lymphoid progenitors to the B cell lineage by
RT antagonizing Notch1.";
RL Immunity 16:231-243(2002).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EP300.
RX PubMed=11564735; DOI=10.1074/jbc.m105245200;
RA Yamamoto N., Yamamoto S., Inagaki F., Kawaichi M., Fukamizu A., Kishi N.,
RA Matsuno K., Nakamura K., Weinmaster G., Okano H., Nakafuku M.;
RT "Role of Deltex-1 as a transcriptional regulator downstream of the Notch
RT receptor.";
RL J. Biol. Chem. 276:45031-45040(2001).
RN [5]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=12753744; DOI=10.1016/s1074-7613(03)00111-0;
RA Saito T., Chiba S., Ichikawa M., Kunisato A., Asai T., Shimizu K.,
RA Yamaguchi T., Yamamoto G., Seo S., Kumano K., Nakagami-Yamaguchi E.,
RA Hamada Y., Aizawa S., Hirai H.;
RT "Notch2 is preferentially expressed in mature B cells and indispensable for
RT marginal zone B lineage development.";
RL Immunity 18:675-685(2003).
RN [6]
RP IN VITRO UBIQUITIN LIGASE ACTIVITY, SUBUNIT, AND INTERACTION WITH BBAP.
RX PubMed=12670957; DOI=10.1074/jbc.m301157200;
RA Takeyama K., Aguiar R.C.T., Gu L., He C., Freeman G.J., Kutok J.L.,
RA Aster J.C., Shipp M.A.;
RT "The BAL-binding protein BBAP and related Deltex family members exhibit
RT ubiquitin-protein isopeptide ligase activity.";
RL J. Biol. Chem. 278:21930-21937(2003).
RN [7]
RP SUBCELLULAR LOCATION, INTERACTION WITH ITCH, AND UBIQUITINATION BY ITCH.
RX PubMed=17028573; DOI=10.1038/sj.embor.7400822;
RA Chastagner P., Israel A., Brou C.;
RT "Itch/AIP4 mediates Deltex degradation through the formation of K29-linked
RT polyubiquitin chains.";
RL EMBO Rep. 7:1147-1153(2006).
RN [8]
RP INTERACTION WITH NOTCH1 AND EIF3F.
RX PubMed=21124883; DOI=10.1371/journal.pbio.1000545;
RA Moretti J., Chastagner P., Gastaldello S., Heuss S.F., Dirac A.M.,
RA Bernards R., Masucci M.G., Israel A., Brou C.;
RT "The translation initiation factor 3f (eIF3f) exhibits a deubiquitinase
RT activity regulating Notch activation.";
RL PLoS Biol. 8:E1000545-E1000545(2010).
CC -!- FUNCTION: Functions as a ubiquitin ligase protein in vivo, mediating
CC ubiquitination and promoting degradation of MEKK1, suggesting that it
CC may regulate the Notch pathway via some ubiquitin ligase activity (By
CC similarity). Regulator of Notch signaling, a signaling pathway involved
CC in cell-cell communications that regulates a broad spectrum of cell-
CC fate determinations. Mainly acts as a positive regulator of Notch, but
CC it also acts as a negative regulator, depending on the developmental
CC and cell context. Mediates the antineural activity of Notch, possibly
CC by inhibiting the transcriptional activation mediated by MATCH1.
CC Involved in neurogenesis, lymphogenesis and myogenesis, and may also be
CC involved in MZB (Marginal zone B) cell differentiation. Promotes B-cell
CC development at the expense of T-cell development, suggesting that it
CC can antagonize NOTCH1. {ECO:0000250, ECO:0000269|PubMed:11564735,
CC ECO:0000269|PubMed:11869684, ECO:0000269|PubMed:9590294}.
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: Homodimer. May form a heterodimer with other members of the
CC Deltex family. Interacts with NOTCH1 via its N-terminal region and
CC EIF3F, the interaction is required for NOTCH1 deubiquitination.
CC Interacts with EP300. Forms a heterodimer with BBAP; the
CC heterodimerization leading to an increase of in vitro ubiquitin ligase
CC activity. Interacts with ITCH. {ECO:0000269|PubMed:11564735,
CC ECO:0000269|PubMed:12670957, ECO:0000269|PubMed:17028573,
CC ECO:0000269|PubMed:21124883, ECO:0000269|PubMed:9590294}.
CC -!- INTERACTION:
CC Q86Y01; P46108: CRK; NbExp=2; IntAct=EBI-1755174, EBI-886;
CC Q86Y01; P10644: PRKAR1A; NbExp=3; IntAct=EBI-1755174, EBI-476431;
CC Q86Y01; P0CG48: UBC; NbExp=2; IntAct=EBI-1755174, EBI-3390054;
CC Q86Y01; Q9DCH4: Eif3f; Xeno; NbExp=9; IntAct=EBI-1755174, EBI-1634316;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly
CC cytoplasmic. Associates with endocytic vesicles. Partially nuclear.
CC -!- TISSUE SPECIFICITY: Widely expressed. Strongly expressed in blood
CC vessel. Also expressed in embryonic nervous system, pancreas, lung,
CC adrenal gland, digestive tube and muscles. Expressed in MZB cells and
CC developing B- and T-cells. {ECO:0000269|PubMed:12753744,
CC ECO:0000269|PubMed:9590294}.
CC -!- INDUCTION: Regulated by NOTCH2. {ECO:0000269|PubMed:12753744}.
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 -!- PTM: Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination
CC catalyzed by ITCH. {ECO:0000269|PubMed:17028573}.
CC -!- SIMILARITY: Belongs to the Deltex family. {ECO:0000305}.
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DR EMBL; AF053700; AAC06246.1; -; mRNA.
DR EMBL; BC005816; AAH05816.2; -; mRNA.
DR EMBL; BC048216; AAH48216.1; -; mRNA.
DR CCDS; CCDS9164.1; -.
DR RefSeq; NP_004407.2; NM_004416.2.
DR RefSeq; XP_011536311.1; XM_011538009.2.
DR PDB; 6Y5N; X-ray; 1.88 A; A/B=388-620.
DR PDB; 6Y5P; X-ray; 1.74 A; A/B=388-620.
DR PDBsum; 6Y5N; -.
DR PDBsum; 6Y5P; -.
DR AlphaFoldDB; Q86Y01; -.
DR SMR; Q86Y01; -.
DR BioGRID; 108173; 29.
DR DIP; DIP-43904N; -.
DR IntAct; Q86Y01; 17.
DR MINT; Q86Y01; -.
DR STRING; 9606.ENSP00000257600; -.
DR iPTMnet; Q86Y01; -.
DR PhosphoSitePlus; Q86Y01; -.
DR BioMuta; DTX1; -.
DR DMDM; 37077046; -.
DR MassIVE; Q86Y01; -.
DR MaxQB; Q86Y01; -.
DR PaxDb; Q86Y01; -.
DR PeptideAtlas; Q86Y01; -.
DR PRIDE; Q86Y01; -.
DR ProteomicsDB; 70344; -.
DR Antibodypedia; 45356; 236 antibodies from 31 providers.
DR DNASU; 1840; -.
DR Ensembl; ENST00000257600.3; ENSP00000257600.3; ENSG00000135144.8.
DR Ensembl; ENST00000548759.2; ENSP00000510707.1; ENSG00000135144.8.
DR GeneID; 1840; -.
DR KEGG; hsa:1840; -.
DR MANE-Select; ENST00000548759.2; ENSP00000510707.1; NM_004416.3; NP_004407.2.
DR UCSC; uc001tuk.2; human.
DR CTD; 1840; -.
DR DisGeNET; 1840; -.
DR GeneCards; DTX1; -.
DR HGNC; HGNC:3060; DTX1.
DR HPA; ENSG00000135144; Tissue enhanced (lymphoid).
DR MIM; 602582; gene.
DR neXtProt; NX_Q86Y01; -.
DR OpenTargets; ENSG00000135144; -.
DR PharmGKB; PA27514; -.
DR VEuPathDB; HostDB:ENSG00000135144; -.
DR eggNOG; ENOG502QQ9M; Eukaryota.
DR GeneTree; ENSGT00940000160943; -.
DR HOGENOM; CLU_030422_4_0_1; -.
DR InParanoid; Q86Y01; -.
DR OMA; QFRQDTX; -.
DR OrthoDB; 600021at2759; -.
DR PhylomeDB; Q86Y01; -.
DR TreeFam; TF325526; -.
DR PathwayCommons; Q86Y01; -.
DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR SignaLink; Q86Y01; -.
DR SIGNOR; Q86Y01; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 1840; 5 hits in 1111 CRISPR screens.
DR ChiTaRS; DTX1; human.
DR GeneWiki; DTX1; -.
DR GenomeRNAi; 1840; -.
DR Pharos; Q86Y01; Tbio.
DR PRO; PR:Q86Y01; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q86Y01; protein.
DR Bgee; ENSG00000135144; Expressed in cortical plate and 129 other tissues.
DR Genevisible; Q86Y01; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005112; F:Notch binding; IDA:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IGI:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; IGI:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc.
DR GO; GO:0006351; P:transcription, DNA-templated; NAS:UniProtKB.
DR CDD; cd09633; Deltex_C; 1.
DR Gene3D; 3.30.390.130; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.30.720.50; -; 2.
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; PTHR12622; 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; SSF117839; SSF117839; 2.
DR PROSITE; PS50918; WWE; 2.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Metal-binding; Notch signaling pathway; Nucleus;
KW Reference proteome; Repeat; SH3-binding; Transferase; Ubl conjugation;
KW Zinc; Zinc-finger.
FT CHAIN 1..620
FT /note="E3 ubiquitin-protein ligase DTX1"
FT /id="PRO_0000219080"
FT DOMAIN 14..94
FT /note="WWE 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT DOMAIN 95..171
FT /note="WWE 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT ZN_FING 411..472
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 221..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 262..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 361..391
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 230..233
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 226..244
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 265..283
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 286..309
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 30
FT /note="W -> C (in Ref. 1; AAC06246)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="A -> V (in Ref. 1; AAC06246)"
FT /evidence="ECO:0000305"
FT CONFLICT 217
FT /note="A -> V (in Ref. 1; AAC06246)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="A -> V (in Ref. 1; AAC06246)"
FT /evidence="ECO:0000305"
FT CONFLICT 618
FT /note="A -> G (in Ref. 1; AAC06246)"
FT /evidence="ECO:0000305"
FT HELIX 392..399
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:6Y5P"
FT TURN 412..414
FT /evidence="ECO:0007829|PDB:6Y5P"
FT HELIX 427..429
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 438..441
FT /evidence="ECO:0007829|PDB:6Y5P"
FT TURN 442..445
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 446..449
FT /evidence="ECO:0007829|PDB:6Y5P"
FT HELIX 450..458
FT /evidence="ECO:0007829|PDB:6Y5P"
FT TURN 459..461
FT /evidence="ECO:0007829|PDB:6Y5P"
FT TURN 469..471
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 474..476
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 486..493
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 504..510
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 520..522
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 525..528
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 533..541
FT /evidence="ECO:0007829|PDB:6Y5P"
FT HELIX 542..556
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 560..564
FT /evidence="ECO:0007829|PDB:6Y5P"
FT TURN 567..569
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 572..577
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 585..587
FT /evidence="ECO:0007829|PDB:6Y5P"
FT STRAND 592..595
FT /evidence="ECO:0007829|PDB:6Y5P"
FT HELIX 600..610
FT /evidence="ECO:0007829|PDB:6Y5P"
SQ SEQUENCE 620 AA; 67368 MW; 3BF3ECE46E25CCD4 CRC64;
MSRPGHGGLM PVNGLGFPPQ NVARVVVWEW LNEHSRWRPY TATVCHHIEN VLKEDARGSV
VLGQVDAQLV PYIIDLQSMH QFRQDTGTMR PVRRNFYDPS SAPGKGIVWE WENDGGAWTA
YDMDICITIQ NAYEKQHPWL DLSSLGFCYL IYFNSMSQMN RQTRRRRRLR RRLDLAYPLT
VGSIPKSQSW PVGASSGQPC SCQQCLLVNS TRAASNAILA SQRRKAPPAP PLPPPPPPGG
PPGALAVRPS ATFTGAALWA APAAGPAEPA PPPGAPPRSP GAPGGARTPG QNNLNRPGPQ
RTTSVSARAS IPPGVPALPV KNLNGTGPVH PALAGMTGIL LCAAGLPVCL TRAPKPILHP
PPVSKSDVKP VPGVPGVCRK TKKKHLKKSK NPEDVVRRYM QKVKNPPDED CTICMERLVT
ASGYEGVLRH KGVRPELVGR LGRCGHMYHL LCLVAMYSNG NKDGSLQCPT CKAIYGEKTG
TQPPGKMEFH LIPHSLPGFP DTQTIRIVYD IPTGIQGPEH PNPGKKFTAR GFPRHCYLPN
NEKGRKVLRL LITAWERRLI FTIGTSNTTG ESDTVVWNEI HHKTEFGSNL TGHGYPDASY
LDNVLAELTA QGVSEAAAKA
