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   27-MAR-2024, entry version 165.
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; 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; 31.
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; 9606-ENSP00000257600; -.
DR   PeptideAtlas; Q86Y01; -.
DR   ProteomicsDB; 70344; -.
DR   Antibodypedia; 45356; 282 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   AGR; HGNC:3060; -.
DR   DisGeNET; 1840; -.
DR   GeneCards; DTX1; -.
DR   HGNC; HGNC:3060; DTX1.
DR   HPA; ENSG00000135144; Tissue enhanced (brain, lymphoid tissue).
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; WEWLSEH; -.
DR   OrthoDB; 5487971at2759; -.
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 1187 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 131 other cell types or tissues.
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:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR   GO; GO:0006351; P:DNA-templated transcription; NAS:UniProtKB.
DR   GO; GO:0010001; P:glial cell differentiation; IEA:Ensembl.
DR   GO; GO:0045665; P:negative regulation of neuron differentiation; IGI:UniProtKB.
DR   GO; GO:0045581; P:negative regulation of T cell differentiation; IEA:Ensembl.
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:0030217; P:T cell differentiation; IEA:Ensembl.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc.
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:SF7; E3 UBIQUITIN-PROTEIN LIGASE DTX1; 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.
DR   Genevisible; Q86Y01; HS.
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
//