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Protein

E3 ubiquitin-protein ligase DTX1

Gene

DTX1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.By similarity3 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri411 – 472RING-typePROSITE-ProRule annotationAdd BLAST62

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • Notch binding Source: UniProtKB
  • transcription coactivator activity Source: ProtInc
  • ubiquitin protein ligase binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • cell surface receptor signaling pathway Source: ProtInc
  • glial cell differentiation Source: Ensembl
  • negative regulation of neuron differentiation Source: UniProtKB
  • negative regulation of T cell differentiation Source: Ensembl
  • Notch signaling pathway Source: Reactome
  • protein ubiquitination Source: UniProtKB-UniPathway
  • regulation of Notch signaling pathway Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB
  • transcription from RNA polymerase II promoter Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Notch signaling pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-2122948. Activated NOTCH1 Transmits Signal to the Nucleus.
SignaLinkiQ86Y01.
SIGNORiQ86Y01.
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
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:3060. DTX1.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Predominantly cytoplasmic. Associates with endocytic vesicles. Partially nuclear.

GO - Cellular componenti

  • cytoplasm Source: ProtInc
  • cytosol Source: Reactome
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi1840.
OpenTargetsiENSG00000135144.
PharmGKBiPA27514.

Polymorphism and mutation databases

BioMutaiDTX1.
DMDMi37077046.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002190801 – 620E3 ubiquitin-protein ligase DTX1Add BLAST620

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

iPTMnetiQ86Y01.
PhosphoSitePlusiQ86Y01.

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

BgeeiENSG00000135144.
CleanExiHS_DTX1.
GenevisibleiQ86Y01. HS.

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

GO - Molecular functioni

  • Notch binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliQ86Y01.
SMRiQ86Y01.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 94WWE 1PROSITE-ProRule annotationAdd BLAST81
Domaini95 – 171WWE 2PROSITE-ProRule annotationAdd BLAST77

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi230 – 233SH3-bindingSequence analysis4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi227 – 375Pro-richAdd BLAST149

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)DescriptionActionsGraphical viewLength
Zinc fingeri411 – 472RING-typePROSITE-ProRule annotationAdd BLAST62

Keywords - Domaini

Repeat, SH3-binding, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IEMS. Eukaryota.
ENOG4111EY2. LUCA.
GeneTreeiENSGT00440000035370.
HOGENOMiHOG000007352.
HOVERGENiHBG007213.
InParanoidiQ86Y01.
KOiK06058.
OMAiGINGMRR.
OrthoDBiEOG091G04KU.
PhylomeDBiQ86Y01.
TreeFamiTF325526.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR004170. WWE-dom.
IPR018123. WWE-dom_subgr.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF02825. WWE. 2 hits.
PF00097. zf-C3HC4. 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

        10         20         30         40         50
MSRPGHGGLM PVNGLGFPPQ NVARVVVWEW LNEHSRWRPY TATVCHHIEN
60 70 80 90 100
VLKEDARGSV VLGQVDAQLV PYIIDLQSMH QFRQDTGTMR PVRRNFYDPS
110 120 130 140 150
SAPGKGIVWE WENDGGAWTA YDMDICITIQ NAYEKQHPWL DLSSLGFCYL
160 170 180 190 200
IYFNSMSQMN RQTRRRRRLR RRLDLAYPLT VGSIPKSQSW PVGASSGQPC
210 220 230 240 250
SCQQCLLVNS TRAASNAILA SQRRKAPPAP PLPPPPPPGG PPGALAVRPS
260 270 280 290 300
ATFTGAALWA APAAGPAEPA PPPGAPPRSP GAPGGARTPG QNNLNRPGPQ
310 320 330 340 350
RTTSVSARAS IPPGVPALPV KNLNGTGPVH PALAGMTGIL LCAAGLPVCL
360 370 380 390 400
TRAPKPILHP PPVSKSDVKP VPGVPGVCRK TKKKHLKKSK NPEDVVRRYM
410 420 430 440 450
QKVKNPPDED CTICMERLVT ASGYEGVLRH KGVRPELVGR LGRCGHMYHL
460 470 480 490 500
LCLVAMYSNG NKDGSLQCPT CKAIYGEKTG TQPPGKMEFH LIPHSLPGFP
510 520 530 540 550
DTQTIRIVYD IPTGIQGPEH PNPGKKFTAR GFPRHCYLPN NEKGRKVLRL
560 570 580 590 600
LITAWERRLI FTIGTSNTTG ESDTVVWNEI HHKTEFGSNL TGHGYPDASY
610 620
LDNVLAELTA QGVSEAAAKA
Length:620
Mass (Da):67,368
Last modified:June 1, 2003 - v1
Checksum:i3BF3ECE46E25CCD4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti30W → C in AAC06246 (PubMed:9590294).Curated1
Sequence conflicti214A → V in AAC06246 (PubMed:9590294).Curated1
Sequence conflicti217A → V in AAC06246 (PubMed:9590294).Curated1
Sequence conflicti226A → V in AAC06246 (PubMed:9590294).Curated1
Sequence conflicti618A → G in AAC06246 (PubMed:9590294).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
XP_011536311.1. XM_011538009.2.
UniGeneiHs.372152.

Genome annotation databases

EnsembliENST00000257600; ENSP00000257600; ENSG00000135144.
GeneIDi1840.
KEGGihsa:1840.
UCSCiuc001tuk.2. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
XP_011536311.1. XM_011538009.2.
UniGeneiHs.372152.

3D structure databases

ProteinModelPortaliQ86Y01.
SMRiQ86Y01.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiQ86Y01.
PhosphoSitePlusiQ86Y01.

Polymorphism and mutation databases

BioMutaiDTX1.
DMDMi37077046.

Proteomic databases

MaxQBiQ86Y01.
PaxDbiQ86Y01.
PeptideAtlasiQ86Y01.
PRIDEiQ86Y01.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257600; ENSP00000257600; ENSG00000135144.
GeneIDi1840.
KEGGihsa:1840.
UCSCiuc001tuk.2. human.

Organism-specific databases

CTDi1840.
DisGeNETi1840.
GeneCardsiDTX1.
HGNCiHGNC:3060. DTX1.
HPAiHPA051249.
MIMi602582. gene.
neXtProtiNX_Q86Y01.
OpenTargetsiENSG00000135144.
PharmGKBiPA27514.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEMS. Eukaryota.
ENOG4111EY2. LUCA.
GeneTreeiENSGT00440000035370.
HOGENOMiHOG000007352.
HOVERGENiHBG007213.
InParanoidiQ86Y01.
KOiK06058.
OMAiGINGMRR.
OrthoDBiEOG091G04KU.
PhylomeDBiQ86Y01.
TreeFamiTF325526.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-HSA-2122948. Activated NOTCH1 Transmits Signal to the Nucleus.
SignaLinkiQ86Y01.
SIGNORiQ86Y01.

Miscellaneous databases

GeneWikiiDTX1.
GenomeRNAii1840.
PROiQ86Y01.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135144.
CleanExiHS_DTX1.
GenevisibleiQ86Y01. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR004170. WWE-dom.
IPR018123. WWE-dom_subgr.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF02825. WWE. 2 hits.
PF00097. zf-C3HC4. 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]
ProtoNetiSearch...

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: November 2, 2016
This is version 122 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.