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Q86Y01

- DTX1_HUMAN

UniProt

Q86Y01 - DTX1_HUMAN

Protein

E3 ubiquitin-protein ligase DTX1

Gene

DTX1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 106 (01 Oct 2014)
      Sequence version 1 (01 Jun 2003)
      Previous versions | rss
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    Functioni

    Functions as a ubiquitin ligase protein in vivo, mediating ubiquitination and promoting degradation of MEKK1, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity By similarity. Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Mainly acts as a positive regulator of Notch, but it also acts as a negative regulator, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Involved in neurogenesis, lymphogenesis and myogenesis, and may also be involved in MZB (Marginal zone B) cell differentiation. Promotes B-cell development at the expense of T-cell development, suggesting that it can antagonize NOTCH1.By similarity3 Publications

    Pathwayi

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri411 – 47262RING-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. ligase activity Source: UniProtKB-KW
    2. Notch binding Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. transcription coactivator activity Source: ProtInc
    5. ubiquitin protein ligase binding Source: UniProtKB
    6. zinc ion binding Source: InterPro

    GO - Biological processi

    1. cell surface receptor signaling pathway Source: ProtInc
    2. glial cell differentiation Source: Ensembl
    3. negative regulation of neuron differentiation Source: UniProtKB
    4. negative regulation of T cell differentiation Source: Ensembl
    5. Notch signaling pathway Source: Reactome
    6. protein ubiquitination Source: UniProtKB-UniPathway
    7. regulation of Notch signaling pathway Source: UniProtKB
    8. regulation of RNA biosynthetic process Source: GOC
    9. transcription, DNA-templated Source: UniProtKB
    10. transcription from RNA polymerase II promoter Source: ProtInc

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Notch signaling pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_194345. Activated NOTCH1 Transmits Signal to the Nucleus.
    SignaLinkiQ86Y01.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 ubiquitin-protein ligase DTX1 (EC:6.3.2.-)
    Alternative name(s):
    Protein deltex-1
    Short name:
    Deltex1
    Short name:
    hDTX1
    Gene namesi
    Name:DTX1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:3060. DTX1.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Predominantly cytoplasmic. Associates with endocytic vesicles. Partially nuclear.

    GO - Cellular componenti

    1. cytoplasm Source: ProtInc
    2. cytosol Source: Reactome
    3. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27514.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 620620E3 ubiquitin-protein ligase DTX1PRO_0000219080Add
    BLAST

    Post-translational modificationi

    Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination catalyzed by ITCH.1 Publication

    Keywords - PTMi

    Ubl conjugation

    Proteomic databases

    MaxQBiQ86Y01.
    PaxDbiQ86Y01.
    PeptideAtlasiQ86Y01.
    PRIDEiQ86Y01.

    PTM databases

    PhosphoSiteiQ86Y01.

    Expressioni

    Tissue specificityi

    Widely expressed. Strongly expressed in blood vessel. Also expressed in embryonic nervous system, pancreas, lung, adrenal gland, digestive tube and muscles. Expressed in MZB cells and developing B- and T-cells.2 Publications

    Inductioni

    Regulated by NOTCH2.1 Publication

    Gene expression databases

    BgeeiQ86Y01.
    CleanExiHS_DTX1.
    GenevestigatoriQ86Y01.

    Organism-specific databases

    HPAiHPA051249.

    Interactioni

    Subunit structurei

    Homodimer. May form a heterodimer with other members of the Deltex family. Interacts with NOTCH1 via its N-terminal region and EIF3F, the interaction is required for NOTCH1 deubiquitination. Interacts with EP300. Forms a heterodimer with BBAP; the heterodimerization leading to an increase of in vitro ubiquitin ligase activity. Interacts with ITCH.5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    UBCP0CG482EBI-1755174,EBI-3390054

    Protein-protein interaction databases

    BioGridi108173. 20 interactions.
    DIPiDIP-43904N.
    IntActiQ86Y01. 15 interactions.
    MINTiMINT-3381012.
    STRINGi9606.ENSP00000257600.

    Structurei

    3D structure databases

    ProteinModelPortaliQ86Y01.
    SMRiQ86Y01. Positions 25-179, 389-613.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini14 – 9481WWE 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini95 – 17177WWE 2PROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi230 – 2334SH3-bindingSequence Analysis

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi227 – 375149Pro-richAdd
    BLAST

    Domaini

    The WWE domains are thought to mediate some protein-protein interaction, and are frequently found in ubiquitin ligases.By similarity

    Sequence similaritiesi

    Belongs to the Deltex family.Curated
    Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
    Contains 2 WWE domains.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri411 – 47262RING-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, SH3-binding, Zinc-finger

    Phylogenomic databases

    eggNOGiNOG84763.
    HOGENOMiHOG000007352.
    HOVERGENiHBG007213.
    InParanoidiQ86Y01.
    KOiK06058.
    OMAiPGFPDTQ.
    OrthoDBiEOG7J17ZB.
    PhylomeDBiQ86Y01.
    TreeFamiTF325526.

    Family and domain databases

    Gene3Di3.30.40.10. 1 hit.
    InterProiIPR004170. WWE-dom.
    IPR018123. WWE-dom_subgr.
    IPR001841. Znf_RING.
    IPR013083. Znf_RING/FYVE/PHD.
    [Graphical view]
    PfamiPF02825. WWE. 2 hits.
    PF13639. zf-RING_2. 1 hit.
    [Graphical view]
    SMARTiSM00184. RING. 1 hit.
    SM00678. WWE. 2 hits.
    [Graphical view]
    PROSITEiPS50918. WWE. 2 hits.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q86Y01-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSRPGHGGLM PVNGLGFPPQ NVARVVVWEW LNEHSRWRPY TATVCHHIEN    50
    VLKEDARGSV VLGQVDAQLV PYIIDLQSMH QFRQDTGTMR PVRRNFYDPS 100
    SAPGKGIVWE WENDGGAWTA YDMDICITIQ NAYEKQHPWL DLSSLGFCYL 150
    IYFNSMSQMN RQTRRRRRLR RRLDLAYPLT VGSIPKSQSW PVGASSGQPC 200
    SCQQCLLVNS TRAASNAILA SQRRKAPPAP PLPPPPPPGG PPGALAVRPS 250
    ATFTGAALWA APAAGPAEPA PPPGAPPRSP GAPGGARTPG QNNLNRPGPQ 300
    RTTSVSARAS IPPGVPALPV KNLNGTGPVH PALAGMTGIL LCAAGLPVCL 350
    TRAPKPILHP PPVSKSDVKP VPGVPGVCRK TKKKHLKKSK NPEDVVRRYM 400
    QKVKNPPDED CTICMERLVT ASGYEGVLRH KGVRPELVGR LGRCGHMYHL 450
    LCLVAMYSNG NKDGSLQCPT CKAIYGEKTG TQPPGKMEFH LIPHSLPGFP 500
    DTQTIRIVYD IPTGIQGPEH PNPGKKFTAR GFPRHCYLPN NEKGRKVLRL 550
    LITAWERRLI FTIGTSNTTG ESDTVVWNEI HHKTEFGSNL TGHGYPDASY 600
    LDNVLAELTA QGVSEAAAKA 620
    Length:620
    Mass (Da):67,368
    Last modified:June 1, 2003 - v1
    Checksum:i3BF3ECE46E25CCD4
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti30 – 301W → C in AAC06246. (PubMed:9590294)Curated
    Sequence conflicti214 – 2141A → V in AAC06246. (PubMed:9590294)Curated
    Sequence conflicti217 – 2171A → V in AAC06246. (PubMed:9590294)Curated
    Sequence conflicti226 – 2261A → V in AAC06246. (PubMed:9590294)Curated
    Sequence conflicti618 – 6181A → G in AAC06246. (PubMed:9590294)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF053700 mRNA. Translation: AAC06246.1.
    BC005816 mRNA. Translation: AAH05816.2.
    BC048216 mRNA. Translation: AAH48216.1.
    CCDSiCCDS9164.1.
    RefSeqiNP_004407.2. NM_004416.2.
    UniGeneiHs.372152.

    Genome annotation databases

    EnsembliENST00000257600; ENSP00000257600; ENSG00000135144.
    GeneIDi1840.
    KEGGihsa:1840.
    UCSCiuc001tuk.1. human.

    Polymorphism databases

    DMDMi37077046.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF053700 mRNA. Translation: AAC06246.1 .
    BC005816 mRNA. Translation: AAH05816.2 .
    BC048216 mRNA. Translation: AAH48216.1 .
    CCDSi CCDS9164.1.
    RefSeqi NP_004407.2. NM_004416.2.
    UniGenei Hs.372152.

    3D structure databases

    ProteinModelPortali Q86Y01.
    SMRi Q86Y01. Positions 25-179, 389-613.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108173. 20 interactions.
    DIPi DIP-43904N.
    IntActi Q86Y01. 15 interactions.
    MINTi MINT-3381012.
    STRINGi 9606.ENSP00000257600.

    PTM databases

    PhosphoSitei Q86Y01.

    Polymorphism databases

    DMDMi 37077046.

    Proteomic databases

    MaxQBi Q86Y01.
    PaxDbi Q86Y01.
    PeptideAtlasi Q86Y01.
    PRIDEi Q86Y01.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000257600 ; ENSP00000257600 ; ENSG00000135144 .
    GeneIDi 1840.
    KEGGi hsa:1840.
    UCSCi uc001tuk.1. human.

    Organism-specific databases

    CTDi 1840.
    GeneCardsi GC12P113495.
    HGNCi HGNC:3060. DTX1.
    HPAi HPA051249.
    MIMi 602582. gene.
    neXtProti NX_Q86Y01.
    PharmGKBi PA27514.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG84763.
    HOGENOMi HOG000007352.
    HOVERGENi HBG007213.
    InParanoidi Q86Y01.
    KOi K06058.
    OMAi PGFPDTQ.
    OrthoDBi EOG7J17ZB.
    PhylomeDBi Q86Y01.
    TreeFami TF325526.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    Reactomei REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_194345. Activated NOTCH1 Transmits Signal to the Nucleus.
    SignaLinki Q86Y01.

    Miscellaneous databases

    GeneWikii DTX1.
    GenomeRNAii 1840.
    NextBioi 7533.
    PROi Q86Y01.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q86Y01.
    CleanExi HS_DTX1.
    Genevestigatori Q86Y01.

    Family and domain databases

    Gene3Di 3.30.40.10. 1 hit.
    InterProi IPR004170. WWE-dom.
    IPR018123. WWE-dom_subgr.
    IPR001841. Znf_RING.
    IPR013083. Znf_RING/FYVE/PHD.
    [Graphical view ]
    Pfami PF02825. WWE. 2 hits.
    PF13639. zf-RING_2. 1 hit.
    [Graphical view ]
    SMARTi SM00184. RING. 1 hit.
    SM00678. WWE. 2 hits.
    [Graphical view ]
    PROSITEi PS50918. WWE. 2 hits.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH NOTCH1.
      Tissue: Fetal brain.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Lymph.
    3. "Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch1."
      Izon D.J., Aster J.C., He Y., Weng A., Karnell F.G., Patriub V., Xu L., Bakkour S., Rodriguez C., Allman D., Pear W.S.
      Immunity 16:231-243(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    4. Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EP300.
    5. "Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development."
      Saito T., Chiba S., Ichikawa M., Kunisato A., Asai T., Shimizu K., Yamaguchi T., Yamamoto G., Seo S., Kumano K., Nakagami-Yamaguchi E., Hamada Y., Aizawa S., Hirai H.
      Immunity 18:675-685(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, INDUCTION.
    6. "The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity."
      Takeyama K., Aguiar R.C.T., Gu L., He C., Freeman G.J., Kutok J.L., Aster J.C., Shipp M.A.
      J. Biol. Chem. 278:21930-21937(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: IN VITRO UBIQUITIN LIGASE ACTIVITY, SUBUNIT, INTERACTION WITH BBAP.
    7. "Itch/AIP4 mediates Deltex degradation through the formation of K29-linked polyubiquitin chains."
      Chastagner P., Israel A., Brou C.
      EMBO Rep. 7:1147-1153(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH ITCH, UBIQUITINATION BY ITCH.
    8. "The translation initiation factor 3f (eIF3f) exhibits a deubiquitinase activity regulating Notch activation."
      Moretti J., Chastagner P., Gastaldello S., Heuss S.F., Dirac A.M., Bernards R., Masucci M.G., Israel A., Brou C.
      PLoS Biol. 8:E1000545-E1000545(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NOTCH1 AND EIF3F.

    Entry informationi

    Entry nameiDTX1_HUMAN
    AccessioniPrimary (citable) accession number: Q86Y01
    Secondary accession number(s): O60630, Q9BS04
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 26, 2003
    Last sequence update: June 1, 2003
    Last modified: October 1, 2014
    This is version 106 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3