Q86Y01 (DTX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	620 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions as an 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 process	Notch signaling pathway
Cellular component	Cytoplasm Nucleus
Domain	Repeat SH3-binding Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Traceable author statement. Source: Reactome glial cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of T cell differentiation Inferred from electronic annotation. Source: Compara 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 transcription from RNA polymerase II promoter Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	Notch 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 zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 620	620	E3 ubiquitin-protein ligase DTX1		PRO_0000219080
Regions
	Domain	14 – 94	81	WWE 1
	Domain	95 – 171	77	WWE 2
	Zinc finger	411 – 472	62	RING-type
	Motif	230 – 233	4	SH3-binding Potential
	Compositional bias	227 – 375	149	Pro-rich
Experimental info
	Sequence conflict	30	1	W → C in AAC06246. Ref.1
	Sequence conflict	214	1	A → V in AAC06246. Ref.1
	Sequence conflict	217	1	A → V in AAC06246. Ref.1
	Sequence conflict	226	1	A → V in AAC06246. Ref.1
	Sequence conflict	618	1	A → G in AAC06246. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q86Y01 [UniParc]. Last modified June 1, 2003. Version 1. Checksum: 3BF3ECE46E25CCD4	FASTA	620	67,368
	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

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00004554.
RefSeq	NP_004407.2. NM_004416.2.
UniGene	Hs.372152.
3D structure databases
ProteinModelPortal	Q86Y01.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-43904N.
IntAct	Q86Y01. 11 interactions.
MINT	MINT-3381012.
STRING	9606.ENSP00000257600.
PTM databases
PhosphoSite	Q86Y01.
Polymorphism databases
DMDM	37077046.
Proteomic databases
PaxDb	Q86Y01.
PeptideAtlas	Q86Y01.
PRIDE	Q86Y01.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257600; ENSP00000257600; ENSG00000135144.
GeneID	1840.
KEGG	hsa:1840.
UCSC	uc001tuk.1. human.
Organism-specific databases
CTD	1840.
GeneCards	GC12P113495.
HGNC	HGNC:3060. DTX1.
HPA	HPA051249.
MIM	602582. gene.
neXtProt	NX_Q86Y01.
PharmGKB	PA27514.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG84763.
HOGENOM	HOG000007352.
HOVERGEN	HBG007213.
InParanoid	Q86Y01.
KO	K06058.
OMA	WPVGASS.
OrthoDB	EOG4QC152.
PhylomeDB	Q86Y01.
Enzyme and pathway databases
Pathway_Interaction_DB	ps1pathway. Presenilin action in Notch and Wnt signaling.
Reactome	REACT_111102. Signal Transduction. REACT_111984. Signal Transduction.
UniPathway	UPA00143.
Gene expression databases
Bgee	Q86Y01.
CleanEx	HS_DTX1.
Genevestigator	Q86Y01.
GermOnline	ENSG00000135144. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR004170. WWE-dom. IPR018123. WWE-dom_subgr. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF02825. WWE. 2 hits. PF13639. zf-RING_2. 1 hit. [Graphical view]
SMART	SM00184. RING. 1 hit. SM00678. WWE. 2 hits. [Graphical view]
PROSITE	PS50918. WWE. 2 hits. PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	1840.
NextBio	7533.
SOURCE	Search...

Entry information

Entry name

DTX1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.