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Protein

Ectonucleoside triphosphate diphosphohydrolase 1

Gene

ENTPD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

In the nervous system, could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission. Could also be implicated in the prevention of platelet aggregation by hydrolyzing platelet-activating ADP to AMP. Hydrolyzes ATP and ADP equally well.1 Publication

Catalytic activityi

A nucleoside 5'-triphosphate + 2 H2O = a nucleoside 5'-phosphate + 2 phosphate.

Cofactori

Ca2+1 Publication, Mg2+1 Publication

pH dependencei

Optimum pH is 7.0-7.5 with ATP as substrate, and 7.5-8.0 with ADP as substrate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei174Proton acceptorBy similarity1

GO - Molecular functioni

GO - Biological processi

  • blood coagulation Source: ProtInc
  • cell adhesion Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

ATP-binding, Calcium, Magnesium, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS06471-MONOMER.
ZFISH:HS06471-MONOMER.
ReactomeiR-HSA-8850843. Phosphate bond hydrolysis by NTPDase proteins.

Names & Taxonomyi

Protein namesi
Recommended name:
Ectonucleoside triphosphate diphosphohydrolase 1 (EC:3.6.1.5)
Short name:
NTPDase 1
Alternative name(s):
Ecto-ATP diphosphohydrolase 1
Short name:
Ecto-ATPDase 1
Short name:
Ecto-ATPase 1
Ecto-apyrase
Lymphoid cell activation antigen
CD_antigen: CD39
Gene namesi
Name:ENTPD1
Synonyms:CD39
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:3363. ENTPD1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 16CytoplasmicSequence analysisAdd BLAST16
Transmembranei17 – 37HelicalSequence analysisAdd BLAST21
Topological domaini38 – 478ExtracellularSequence analysisAdd BLAST441
Transmembranei479 – 499HelicalSequence analysisAdd BLAST21
Topological domaini500 – 510CytoplasmicSequence analysisAdd BLAST11

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • membrane Source: UniProtKB
  • plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Spastic paraplegia 64, autosomal recessive (SPG64)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
See also OMIM:615683
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071082210G → R in SPG64. 1 Publication1

Keywords - Diseasei

Disease mutation, Hereditary spastic paraplegia, Neurodegeneration

Organism-specific databases

DisGeNETi953.
MalaCardsiENTPD1.
MIMi615683. phenotype.
OpenTargetsiENSG00000138185.
ENSG00000282889.
Orphaneti401810. Autosomal recessive spastic paraplegia type 64.
PharmGKBiPA27798.

Chemistry databases

ChEMBLiCHEMBL5722.
GuidetoPHARMACOLOGYi2888.

Polymorphism and mutation databases

BioMutaiENTPD1.
DMDMi1705710.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002099021 – 510Ectonucleoside triphosphate diphosphohydrolase 1Add BLAST510

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi13S-palmitoyl cysteine1 Publication1
Glycosylationi73N-linked (GlcNAc...)1 Publication1
Disulfide bondi84 ↔ 108By similarity
Glycosylationi227N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi255 ↔ 301By similarity
Disulfide bondi282 ↔ 325By similarity
Glycosylationi292N-linked (GlcNAc...)1 Publication1
Glycosylationi334N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi338 ↔ 343By similarity
Glycosylationi371N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi390 ↔ 413By similarity
Glycosylationi457N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

The N-terminus is blocked.
Palmitoylated in the N-terminal part.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

MaxQBiP49961.
PaxDbiP49961.
PeptideAtlasiP49961.
PRIDEiP49961.

PTM databases

iPTMnetiP49961.
PhosphoSitePlusiP49961.
SwissPalmiP49961.

Expressioni

Tissue specificityi

Expressed primarily on activated lymphoid cells. Also expressed in endothelial tissues. Isoform 1 and isoform 3 are present in both placenta and umbilical vein, whereas isoform 2 is present in placenta only.

Gene expression databases

BgeeiENSG00000138185.
CleanExiHS_ENTPD1.
ExpressionAtlasiP49961. baseline and differential.
GenevisibleiP49961. HS.

Organism-specific databases

HPAiCAB002494.
HPA014067.

Interactioni

Subunit structurei

Homodimer; disulfide-linked.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
RANBP9Q96S595EBI-8074749,EBI-636085

Protein-protein interaction databases

BioGridi107391. 1 interactor.
IntActiP49961. 1 interactor.
MINTiMINT-8215689.
STRINGi9606.ENSP00000360250.

Chemistry databases

BindingDBiP49961.

Structurei

3D structure databases

ProteinModelPortaliP49961.
SMRiP49961.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the GDA1/CD39 NTPase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1386. Eukaryota.
COG5371. LUCA.
GeneTreeiENSGT00550000074435.
HOGENOMiHOG000059572.
HOVERGENiHBG018982.
InParanoidiP49961.
KOiK01510.
OMAiPSYFWKE.
OrthoDBiEOG091G05FZ.
PhylomeDBiP49961.
TreeFamiTF332859.

Family and domain databases

InterProiIPR000407. GDA1_CD39_NTPase.
[Graphical view]
PANTHERiPTHR11782. PTHR11782. 1 hit.
PfamiPF01150. GDA1_CD39. 1 hit.
[Graphical view]
PROSITEiPS01238. GDA1_CD39_NTPASE. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49961-1) [UniParc]FASTAAdd to basket
Also known as: Vascular

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEDTKESNVK TFCSKNILAI LGFSSIIAVI ALLAVGLTQN KALPENVKYG
60 70 80 90 100
IVLDAGSSHT SLYIYKWPAE KENDTGVVHQ VEECRVKGPG ISKFVQKVNE
110 120 130 140 150
IGIYLTDCME RAREVIPRSQ HQETPVYLGA TAGMRLLRME SEELADRVLD
160 170 180 190 200
VVERSLSNYP FDFQGARIIT GQEEGAYGWI TINYLLGKFS QKTRWFSIVP
210 220 230 240 250
YETNNQETFG ALDLGGASTQ VTFVPQNQTI ESPDNALQFR LYGKDYNVYT
260 270 280 290 300
HSFLCYGKDQ ALWQKLAKDI QVASNEILRD PCFHPGYKKV VNVSDLYKTP
310 320 330 340 350
CTKRFEMTLP FQQFEIQGIG NYQQCHQSIL ELFNTSYCPY SQCAFNGIFL
360 370 380 390 400
PPLQGDFGAF SAFYFVMKFL NLTSEKVSQE KVTEMMKKFC AQPWEEIKTS
410 420 430 440 450
YAGVKEKYLS EYCFSGTYIL SLLLQGYHFT ADSWEHIHFI GKIQGSDAGW
460 470 480 490 500
TLGYMLNLTN MIPAEQPLST PLSHSTYVFL MVLFSLVLFT VAIIGLLIFH
510
KPSYFWKDMV
Length:510
Mass (Da):57,965
Last modified:October 1, 1996 - v1
Checksum:iBAD87D2499649159
GO
Isoform 2 (identifier: P49961-2) [UniParc]FASTAAdd to basket
Also known as: Placental I

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MEDT → MKGTKDLTSQQ

Show »
Length:517
Mass (Da):58,706
Checksum:i3E6C59E474010921
GO
Isoform 3 (identifier: P49961-3) [UniParc]FASTAAdd to basket
Also known as: Placental II

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MEDT → MKGTKDLTSQQ
     272-299: VASNEILRDPCFHPGYKKVVNVSDLYKT → ASITQSRPAPFTSAPPAPTSCCFLFQIQ
     300-510: Missing.

Show »
Length:306
Mass (Da):34,175
Checksum:iE0D3B642D3A5A6C8
GO
Isoform 4 (identifier: P49961-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-138: Missing.

Show »
Length:372
Mass (Da):42,731
Checksum:iA8B1DE1366356EE3
GO
Isoform 5 (identifier: P49961-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.

Show »
Length:402
Mass (Da):46,180
Checksum:iF5CE35BD50FF7DB3
GO
Isoform 6 (identifier: P49961-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-5: MEDTK → MGREELFLTFSFSSGFQ

Note: No experimental confirmation available.
Show »
Length:522
Mass (Da):59,325
Checksum:i5D160D81F02277B7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57 – 58SS → G AA sequence (PubMed:9846014).Curated2
Sequence conflicti162D → K AA sequence (PubMed:8529670).Curated1
Sequence conflicti208T → TGET AA sequence (PubMed:9846014).Curated1
Sequence conflicti248V → Y AA sequence (PubMed:9846014).Curated1
Sequence conflicti481M → I in BAG62981 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071082210G → R in SPG64. 1 Publication1
Natural variantiVAR_022099293V → I.Corresponds to variant rs3793744dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0442841 – 138Missing in isoform 4. 2 PublicationsAdd BLAST138
Alternative sequenceiVSP_0442831 – 108Missing in isoform 5. 1 PublicationAdd BLAST108
Alternative sequenceiVSP_0460501 – 5MEDTK → MGREELFLTFSFSSGFQ in isoform 6. 1 Publication5
Alternative sequenceiVSP_0036071 – 4MEDT → MKGTKDLTSQQ in isoform 2 and isoform 3. 1 Publication4
Alternative sequenceiVSP_003608272 – 299VASNE…DLYKT → ASITQSRPAPFTSAPPAPTS CCFLFQIQ in isoform 3. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_003609300 – 510Missing in isoform 3. 1 PublicationAdd BLAST211

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S73813 mRNA. Translation: AAB32152.1.
U87967 mRNA. Translation: AAB47572.1.
AK304836 mRNA. Translation: BAG65580.1.
AJ133133 mRNA. Translation: CAB41886.1.
AJ133134 mRNA. Translation: CAB41887.1.
AK298648 mRNA. Translation: BAH12835.1.
AK301459 mRNA. Translation: BAG62981.1.
AK304018 mRNA. Translation: BAG64933.1.
AK316009 mRNA. Translation: BAH14380.1.
AL356632, AL365273 Genomic DNA. Translation: CAI16771.1.
AL365273 Genomic DNA. Translation: CAH73752.1.
AL365273, AL356632 Genomic DNA. Translation: CAH73753.1.
AL365273, AL356632 Genomic DNA. Translation: CAH73754.1.
AL356632, AL365273 Genomic DNA. Translation: CAI16770.1.
CH471066 Genomic DNA. Translation: EAW49988.1.
CH471066 Genomic DNA. Translation: EAW49989.1.
CH471066 Genomic DNA. Translation: EAW49990.1.
BC047664 mRNA. Translation: AAH47664.1.
CCDSiCCDS41554.1. [P49961-2]
CCDS53556.1. [P49961-6]
CCDS53557.1. [P49961-5]
CCDS53558.1. [P49961-4]
CCDS7444.1. [P49961-1]
PIRiI56242.
RefSeqiNP_001091645.1. NM_001098175.1. [P49961-2]
NP_001157650.1. NM_001164178.1. [P49961-6]
NP_001157653.1. NM_001164181.1. [P49961-5]
NP_001157654.1. NM_001164182.1. [P49961-4]
NP_001157655.1. NM_001164183.1. [P49961-4]
NP_001299583.1. NM_001312654.1. [P49961-5]
NP_001307845.1. NM_001320916.1.
NP_001767.3. NM_001776.5. [P49961-1]
XP_011538673.1. XM_011540371.2. [P49961-2]
XP_011538679.1. XM_011540377.2. [P49961-5]
XP_016872448.1. XM_017016959.1. [P49961-4]
UniGeneiHs.576612.
Hs.722260.

Genome annotation databases

EnsembliENST00000371205; ENSP00000360248; ENSG00000138185. [P49961-1]
ENST00000371207; ENSP00000360250; ENSG00000138185. [P49961-6]
ENST00000453258; ENSP00000390955; ENSG00000138185. [P49961-2]
ENST00000543964; ENSP00000442968; ENSG00000138185. [P49961-5]
GeneIDi953.
KEGGihsa:953.
UCSCiuc001klh.5. human. [P49961-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S73813 mRNA. Translation: AAB32152.1.
U87967 mRNA. Translation: AAB47572.1.
AK304836 mRNA. Translation: BAG65580.1.
AJ133133 mRNA. Translation: CAB41886.1.
AJ133134 mRNA. Translation: CAB41887.1.
AK298648 mRNA. Translation: BAH12835.1.
AK301459 mRNA. Translation: BAG62981.1.
AK304018 mRNA. Translation: BAG64933.1.
AK316009 mRNA. Translation: BAH14380.1.
AL356632, AL365273 Genomic DNA. Translation: CAI16771.1.
AL365273 Genomic DNA. Translation: CAH73752.1.
AL365273, AL356632 Genomic DNA. Translation: CAH73753.1.
AL365273, AL356632 Genomic DNA. Translation: CAH73754.1.
AL356632, AL365273 Genomic DNA. Translation: CAI16770.1.
CH471066 Genomic DNA. Translation: EAW49988.1.
CH471066 Genomic DNA. Translation: EAW49989.1.
CH471066 Genomic DNA. Translation: EAW49990.1.
BC047664 mRNA. Translation: AAH47664.1.
CCDSiCCDS41554.1. [P49961-2]
CCDS53556.1. [P49961-6]
CCDS53557.1. [P49961-5]
CCDS53558.1. [P49961-4]
CCDS7444.1. [P49961-1]
PIRiI56242.
RefSeqiNP_001091645.1. NM_001098175.1. [P49961-2]
NP_001157650.1. NM_001164178.1. [P49961-6]
NP_001157653.1. NM_001164181.1. [P49961-5]
NP_001157654.1. NM_001164182.1. [P49961-4]
NP_001157655.1. NM_001164183.1. [P49961-4]
NP_001299583.1. NM_001312654.1. [P49961-5]
NP_001307845.1. NM_001320916.1.
NP_001767.3. NM_001776.5. [P49961-1]
XP_011538673.1. XM_011540371.2. [P49961-2]
XP_011538679.1. XM_011540377.2. [P49961-5]
XP_016872448.1. XM_017016959.1. [P49961-4]
UniGeneiHs.576612.
Hs.722260.

3D structure databases

ProteinModelPortaliP49961.
SMRiP49961.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107391. 1 interactor.
IntActiP49961. 1 interactor.
MINTiMINT-8215689.
STRINGi9606.ENSP00000360250.

Chemistry databases

BindingDBiP49961.
ChEMBLiCHEMBL5722.
GuidetoPHARMACOLOGYi2888.

PTM databases

iPTMnetiP49961.
PhosphoSitePlusiP49961.
SwissPalmiP49961.

Polymorphism and mutation databases

BioMutaiENTPD1.
DMDMi1705710.

Proteomic databases

MaxQBiP49961.
PaxDbiP49961.
PeptideAtlasiP49961.
PRIDEiP49961.

Protocols and materials databases

DNASUi953.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000371205; ENSP00000360248; ENSG00000138185. [P49961-1]
ENST00000371207; ENSP00000360250; ENSG00000138185. [P49961-6]
ENST00000453258; ENSP00000390955; ENSG00000138185. [P49961-2]
ENST00000543964; ENSP00000442968; ENSG00000138185. [P49961-5]
GeneIDi953.
KEGGihsa:953.
UCSCiuc001klh.5. human. [P49961-1]

Organism-specific databases

CTDi953.
DisGeNETi953.
GeneCardsiENTPD1.
HGNCiHGNC:3363. ENTPD1.
HPAiCAB002494.
HPA014067.
MalaCardsiENTPD1.
MIMi601752. gene.
615683. phenotype.
neXtProtiNX_P49961.
OpenTargetsiENSG00000138185.
ENSG00000282889.
Orphaneti401810. Autosomal recessive spastic paraplegia type 64.
PharmGKBiPA27798.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1386. Eukaryota.
COG5371. LUCA.
GeneTreeiENSGT00550000074435.
HOGENOMiHOG000059572.
HOVERGENiHBG018982.
InParanoidiP49961.
KOiK01510.
OMAiPSYFWKE.
OrthoDBiEOG091G05FZ.
PhylomeDBiP49961.
TreeFamiTF332859.

Enzyme and pathway databases

BioCyciMetaCyc:HS06471-MONOMER.
ZFISH:HS06471-MONOMER.
ReactomeiR-HSA-8850843. Phosphate bond hydrolysis by NTPDase proteins.

Miscellaneous databases

ChiTaRSiENTPD1. human.
GeneWikiiENTPD1.
GenomeRNAii953.
PROiP49961.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138185.
CleanExiHS_ENTPD1.
ExpressionAtlasiP49961. baseline and differential.
GenevisibleiP49961. HS.

Family and domain databases

InterProiIPR000407. GDA1_CD39_NTPase.
[Graphical view]
PANTHERiPTHR11782. PTHR11782. 1 hit.
PfamiPF01150. GDA1_CD39. 1 hit.
[Graphical view]
PROSITEiPS01238. GDA1_CD39_NTPASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiENTP1_HUMAN
AccessioniPrimary (citable) accession number: P49961
Secondary accession number(s): A9Z1X8
, B4DWB9, B4E1X1, B7Z599, G3XAF6, Q5T561, Q5T562, Q86VV3, Q9UQQ9, Q9Y3Q9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 164 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, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. 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.