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Q86Y01 (DTX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase DTX1

EC=6.3.2.-
Alternative name(s):
Protein deltex-1
Short name=Deltex1
Short name=hDTX1
Gene names
Name:DTX1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length620 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.3 Ref.4

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Homodimer. May form a heterodimer with other members of the Deltex family. Interacts with NOTCH1 via its N-terminus 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. Ref.1 Ref.4 Ref.6 Ref.7 Ref.8

Subcellular location

Cytoplasm. Nucleus. Note: Predominantly cytoplasmic. Associates with endocytic vesicles. Partially nuclear. Ref.1 Ref.4 Ref.7

Tissue specificity

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. Ref.1 Ref.5

Induction

Regulated by NOTCH2. Ref.5

Domain

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

Post-translational modification

Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination catalyzed by ITCH. Ref.7

Sequence similarities

Belongs to the Deltex family.

Contains 1 RING-type zinc finger.

Contains 2 WWE domains.

Ontologies

Keywords
   Biological processNotch signaling pathway
   Cellular componentCytoplasm
Nucleus
   DomainRepeat
SH3-binding
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   PTMUbl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch signaling pathway

Traceable author statement. Source: Reactome

cell surface receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

glial cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of T cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron differentiation

Inferred from genetic interaction Ref.4. Source: UniProtKB

protein ubiquitination

Inferred from electronic annotation. Source: UniProtKB-UniPathway

regulation of Notch signaling pathway

Inferred from genetic interaction Ref.4. Source: UniProtKB

regulation of RNA biosynthetic process

Traceable author statement Ref.1. Source: GOC

transcription from RNA polymerase II promoter

Traceable author statement Ref.1. Source: ProtInc

transcription, DNA-templated

Non-traceable author statement Ref.4. Source: UniProtKB

   Cellular_componentcytoplasm

Traceable author statement Ref.1. Source: ProtInc

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionNotch binding

Inferred from direct assay Ref.4. Source: UniProtKB

ligase activity

Inferred from electronic annotation. Source: UniProtKB-KW

transcription coactivator activity

Traceable author statement Ref.1. Source: ProtInc

ubiquitin protein ligase binding

Inferred from physical interaction Ref.7. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

UBCP0CG482EBI-1755174,EBI-3390054

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 620620E3 ubiquitin-protein ligase DTX1
PRO_0000219080

Regions

Domain14 – 9481WWE 1
Domain95 – 17177WWE 2
Zinc finger411 – 47262RING-type
Motif230 – 2334SH3-binding Potential
Compositional bias227 – 375149Pro-rich

Experimental info

Sequence conflict301W → C in AAC06246. Ref.1
Sequence conflict2141A → V in AAC06246. Ref.1
Sequence conflict2171A → V in AAC06246. Ref.1
Sequence conflict2261A → V in AAC06246. Ref.1
Sequence conflict6181A → G in AAC06246. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q86Y01 [UniParc].

Last modified June 1, 2003. Version 1.
Checksum: 3BF3ECE46E25CCD4

FASTA62067,368
        10         20         30         40         50         60 
MSRPGHGGLM PVNGLGFPPQ NVARVVVWEW LNEHSRWRPY TATVCHHIEN VLKEDARGSV 

        70         80         90        100        110        120 
VLGQVDAQLV PYIIDLQSMH QFRQDTGTMR PVRRNFYDPS SAPGKGIVWE WENDGGAWTA 

       130        140        150        160        170        180 
YDMDICITIQ NAYEKQHPWL DLSSLGFCYL IYFNSMSQMN RQTRRRRRLR RRLDLAYPLT 

       190        200        210        220        230        240 
VGSIPKSQSW PVGASSGQPC SCQQCLLVNS TRAASNAILA SQRRKAPPAP PLPPPPPPGG 

       250        260        270        280        290        300 
PPGALAVRPS ATFTGAALWA APAAGPAEPA PPPGAPPRSP GAPGGARTPG QNNLNRPGPQ 

       310        320        330        340        350        360 
RTTSVSARAS IPPGVPALPV KNLNGTGPVH PALAGMTGIL LCAAGLPVCL TRAPKPILHP 

       370        380        390        400        410        420 
PPVSKSDVKP VPGVPGVCRK TKKKHLKKSK NPEDVVRRYM QKVKNPPDED CTICMERLVT 

       430        440        450        460        470        480 
ASGYEGVLRH KGVRPELVGR LGRCGHMYHL LCLVAMYSNG NKDGSLQCPT CKAIYGEKTG 

       490        500        510        520        530        540 
TQPPGKMEFH LIPHSLPGFP DTQTIRIVYD IPTGIQGPEH PNPGKKFTAR GFPRHCYLPN 

       550        560        570        580        590        600 
NEKGRKVLRL LITAWERRLI FTIGTSNTTG ESDTVVWNEI HHKTEFGSNL TGHGYPDASY 

       610        620 
LDNVLAELTA QGVSEAAAKA 

« Hide

References

« Hide 'large scale' references
[1]"Human deltex is a conserved regulator of Notch signalling."
Matsuno K., Eastman D., Mitsiades T., Quinn A.M., Carcanciu M.L., Ordentlich P., Kadesch T., Artavanis-Tsakonas S.
Nat. Genet. 19:74-78(1998) [PubMed] [Europe PMC] [Abstract]
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]"Role of Deltex-1 as a transcriptional regulator downstream of the Notch receptor."
Yamamoto N., Yamamoto S., Inagaki F., Kawaichi M., Fukamizu A., Kishi N., Matsuno K., Nakamura K., Weinmaster G., Okano H., Nakafuku M.
J. Biol. Chem. 276:45031-45040(2001) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF053700 mRNA. Translation: AAC06246.1.
BC005816 mRNA. Translation: AAH05816.2.
BC048216 mRNA. Translation: AAH48216.1.
RefSeqNP_004407.2. NM_004416.2.
UniGeneHs.372152.

3D structure databases

ProteinModelPortalQ86Y01.
SMRQ86Y01. Positions 25-179, 389-613.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108173. 20 interactions.
DIPDIP-43904N.
IntActQ86Y01. 15 interactions.
MINTMINT-3381012.
STRING9606.ENSP00000257600.

PTM databases

PhosphoSiteQ86Y01.

Polymorphism databases

DMDM37077046.

Proteomic databases

PaxDbQ86Y01.
PeptideAtlasQ86Y01.
PRIDEQ86Y01.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000257600; ENSP00000257600; ENSG00000135144.
GeneID1840.
KEGGhsa:1840.
UCSCuc001tuk.1. human.

Organism-specific databases

CTD1840.
GeneCardsGC12P113495.
HGNCHGNC:3060. DTX1.
HPAHPA051249.
MIM602582. gene.
neXtProtNX_Q86Y01.
PharmGKBPA27514.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG84763.
HOGENOMHOG000007352.
HOVERGENHBG007213.
InParanoidQ86Y01.
KOK06058.
OMAPGFPDTQ.
OrthoDBEOG7J17ZB.
PhylomeDBQ86Y01.
TreeFamTF325526.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
SignaLinkQ86Y01.
UniPathwayUPA00143.

Gene expression databases

BgeeQ86Y01.
CleanExHS_DTX1.
GenevestigatorQ86Y01.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR004170. WWE-dom.
IPR018123. WWE-dom_subgr.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF02825. WWE. 2 hits.
PF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
SM00678. WWE. 2 hits.
[Graphical view]
PROSITEPS50918. WWE. 2 hits.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiDTX1.
GenomeRNAi1840.
NextBio7533.
PROQ86Y01.
SOURCESearch...

Entry information

Entry nameDTX1_HUMAN
AccessionPrimary (citable) accession number: Q86Y01
Secondary accession number(s): O60630, Q9BS04
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: June 1, 2003
Last modified: April 16, 2014
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM