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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

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. transcription coactivator activity Source: ProtInc
  4. ubiquitin protein ligase binding Source: UniProtKB
  5. 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 nucleic acid-templated transcription Source: GOC
  9. transcription, DNA-templated Source: UniProtKB
  10. 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

ReactomeiREACT_118614. 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 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

  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 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. 21 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.
GeneTreeiENSGT00440000035370.
HOGENOMiHOG000007352.
HOVERGENiHBG007213.
InParanoidiQ86Y01.
KOiK06058.
OMAiYSAAVCH.
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

        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)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:
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.
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:
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.
UniGeneiHs.372152.

3D structure databases

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

Protein-protein interaction databases

BioGridi108173. 21 interactions.
DIPiDIP-43904N.
IntActiQ86Y01. 15 interactions.
MINTiMINT-3381012.
STRINGi9606.ENSP00000257600.

PTM databases

PhosphoSiteiQ86Y01.

Polymorphism databases

DMDMi37077046.

Proteomic databases

MaxQBiQ86Y01.
PaxDbiQ86Y01.
PeptideAtlasiQ86Y01.
PRIDEiQ86Y01.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1840.
GeneCardsiGC12P113495.
HGNCiHGNC:3060. DTX1.
HPAiHPA051249.
MIMi602582. gene.
neXtProtiNX_Q86Y01.
PharmGKBiPA27514.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG84763.
GeneTreeiENSGT00440000035370.
HOGENOMiHOG000007352.
HOVERGENiHBG007213.
InParanoidiQ86Y01.
KOiK06058.
OMAiYSAAVCH.
OrthoDBiEOG7J17ZB.
PhylomeDBiQ86Y01.
TreeFamiTF325526.

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiDTX1.
GenomeRNAii1840.
NextBioi7533.
PROiQ86Y01.
SOURCEiSearch...

Gene expression databases

BgeeiQ86Y01.
CleanExiHS_DTX1.
GenevestigatoriQ86Y01.

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]
ProtoNetiSearch...

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(2003) [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(2001) [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(2002) [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(2002) [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(2005) [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(2009) [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: January 7, 2015
This is version 109 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

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 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.