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Protein

Ectonucleoside triphosphate diphosphohydrolase 1

Gene

ENTPD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • nucleobase-containing small molecule catabolic process Source: Reactome

Keywordsi

Molecular functionHydrolase
LigandATP-binding, Calcium, Magnesium, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc: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

EuPathDBiHostDB:ENSG00000138185.17
HostDB:ENSG00000282889.1
HGNCiHGNC:3363 ENTPD1
MIMi601752 gene
neXtProtiNX_P49961

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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
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...) asparagine1 Publication1
Disulfide bondi84 ↔ 108By similarity
Glycosylationi227N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi255 ↔ 301By similarity
Disulfide bondi282 ↔ 325By similarity
Glycosylationi292N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi334N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi338 ↔ 343By similarity
Glycosylationi371N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi390 ↔ 413By similarity
Glycosylationi457N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi56188
56189 [P49961-2]
56190 [P49961-3]

PTM databases

GlyConnecti1192
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 Expressed in 222 organ(s), highest expression level in tendon of biceps brachii
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, 2 interactors
CORUMiP49961
IntActiP49961, 1 interactor
MINTiP49961
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
OMAiKPSYFWK
OrthoDBiEOG091G05FZ
PhylomeDBiP49961
TreeFamiTF332859

Family and domain databases

InterProiView protein in InterPro
IPR000407 GDA1_CD39_NTPase
PANTHERiPTHR11782 PTHR11782, 1 hit
PfamiView protein in Pfam
PF01150 GDA1_CD39, 1 hit
PROSITEiView protein in PROSITE
PS01238 GDA1_CD39_NTPASE, 1 hit

Sequences (6+)i

Sequence statusi: Complete.

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

This entry has 6 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1W2PQK8A0A1W2PQK8_HUMAN
Ectonucleoside triphosphate diphosp...
ENTPD1
147Annotation score:
A0A0U1RR44A0A0U1RR44_HUMAN
Ectonucleoside triphosphate diphosp...
ENTPD1
63Annotation score:
A0A0U1RQZ5A0A0U1RQZ5_HUMAN
Ectonucleoside triphosphate diphosp...
ENTPD1
51Annotation score:

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 dbSNP:rs3793744Ensembl.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 Genomic DNA No translation available.
AL365273 Genomic DNA No translation available.
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]
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

Similar proteinsi

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 Genomic DNA No translation available.
AL365273 Genomic DNA No translation available.
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]
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, 2 interactors
CORUMiP49961
IntActiP49961, 1 interactor
MINTiP49961
STRINGi9606.ENSP00000360250

Chemistry databases

BindingDBiP49961
ChEMBLiCHEMBL5722
GuidetoPHARMACOLOGYi2888

PTM databases

GlyConnecti1192
iPTMnetiP49961
PhosphoSitePlusiP49961
SwissPalmiP49961

Polymorphism and mutation databases

BioMutaiENTPD1
DMDMi1705710

Proteomic databases

MaxQBiP49961
PaxDbiP49961
PeptideAtlasiP49961
PRIDEiP49961
ProteomicsDBi56188
56189 [P49961-2]
56190 [P49961-3]

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
EuPathDBiHostDB:ENSG00000138185.17
HostDB:ENSG00000282889.1
GeneCardsiENTPD1
HGNCiHGNC:3363 ENTPD1
HPAiCAB002494
HPA014067
MalaCardsiENTPD1
MIMi601752 gene
615683 phenotype
neXtProtiNX_P49961
OpenTargetsiENSG00000138185
Orphaneti401810 Autosomal recessive spastic paraplegia type 64
PharmGKBiPA27798
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiENTPD1 human
GeneWikiiENTPD1
GenomeRNAii953
PROiPR:P49961
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138185 Expressed in 222 organ(s), highest expression level in tendon of biceps brachii
CleanExiHS_ENTPD1
ExpressionAtlasiP49961 baseline and differential
GenevisibleiP49961 HS

Family and domain databases

InterProiView protein in InterPro
IPR000407 GDA1_CD39_NTPase
PANTHERiPTHR11782 PTHR11782, 1 hit
PfamiView protein in Pfam
PF01150 GDA1_CD39, 1 hit
PROSITEiView protein in PROSITE
PS01238 GDA1_CD39_NTPASE, 1 hit
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 historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: October 10, 2018
This is version 178 of the entry and version 1 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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