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Q86Y01

- DTX1_HUMAN

UniProt

Q86Y01 - DTX1_HUMAN

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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

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 NOTCH1.3 Publications

Pathwayi

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri411 – 47262RING-type
Add
BLAST

GO - Molecular functioni

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

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.3 Publications

GO - Cellular componenti

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

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 DTX1
PRO_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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 9481WWE 1
Add
BLAST
Domaini95 – 17177WWE 2
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi230 – 2334SH3-binding Reviewed prediction

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi227 – 375149Pro-rich
Add
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.
Contains 2 WWE domains.

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti30 – 301W → C in AAC06246. 1 Publication
Sequence conflicti214 – 2141A → V in AAC06246. 1 Publication
Sequence conflicti217 – 2171A → V in AAC06246. 1 Publication
Sequence conflicti226 – 2261A → V in AAC06246. 1 Publication
Sequence conflicti618 – 6181A → G in AAC06246. 1 Publication

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 105 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

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