P49961 (ENTP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ectonucleoside triphosphate diphosphohydrolase 1
Short name=NTPDase 1
EC=3.6.1.5

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 names

Name:	ENTPD1
Synonyms:	CD39

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	510 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	In the nervous system, could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission. Could also be implicated in the prevention of platelet aggregation. Hydrolyzes ATP and ADP equally well. Ref.9
Catalytic activity	ATP + 2 H2O = AMP + 2 phosphate.
Cofactor	Calcium. Magnesium.
Subunit structure	Homodimer; disulfide-linked By similarity.
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Expressed primarily on activated lymphoid cells. Also expressed in endothelial tissues. The vascular isoform and the placental isoform II are present in both placenta and umbilical vein, whereas placental isoform I is present in placenta only.
Post-translational modification	The N-terminus is blocked. Palmitoylated in the N-terminal part. Ref.11
Sequence similarities	Belongs to the GDA1/CD39 NTPase family.
Biophysicochemical properties	pH dependence: Optimum pH is 7.0-7.5 with ATP as substrate, and 7.5-8.0 with ADP as substrate.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Calcium Magnesium Nucleotide-binding
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	blood coagulation Traceable author statement. Source: ProtInc cell adhesion Non-traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW hydrolase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Vascular (identifier: P49961-1)

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.

Isoform Placental I (identifier: P49961-2)

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

Isoform Placental II (identifier: P49961-3)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 510	510	Ectonucleoside triphosphate diphosphohydrolase 1		PRO_0000209902
Regions
	Topological domain	1 – 16	16	Cytoplasmic Potential
	Transmembrane	17 – 37	21	Helical; Potential
	Topological domain	38 – 478	441	Extracellular Potential
	Transmembrane	479 – 499	21	Helical; Potential
	Topological domain	500 – 510	11	Cytoplasmic Potential
Sites
	Active site	174	1	Proton acceptor By similarity
Amino acid modifications
	Modified residue	49	1	Phosphotyrosine Ref.12
	Modified residue	65	1	Phosphotyrosine Ref.12
	Lipidation	13	1	S-palmitoyl cysteine Probable
	Glycosylation	73	1	N-linked (GlcNAc...) Ref.13
	Glycosylation	227	1	N-linked (GlcNAc...) Potential
	Glycosylation	292	1	N-linked (GlcNAc...) Ref.13
	Glycosylation	334	1	N-linked (GlcNAc...) Potential
	Glycosylation	371	1	N-linked (GlcNAc...) Potential
	Glycosylation	457	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 4	4	MEDT → MKGTKDLTSQQ in isoform Placental I and isoform Placental II.		VSP_003607
	Alternative sequence	272 – 299	28	VASNE…DLYKT → ASITQSRPAPFTSAPPAPTS CCFLFQIQ in isoform Placental II.		VSP_003608
	Alternative sequence	300 – 510	211	Missing in isoform Placental II.		VSP_003609
	Natural variant	293	1	V → I. Corresponds to variant rs3793744 [ dbSNP | Ensembl ].		VAR_022099
Experimental info
	Sequence conflict	57 – 58	2	SS → G AA sequence Ref.8
	Sequence conflict	162	1	D → K AA sequence Ref.7
	Sequence conflict	208	1	T → TGET AA sequence Ref.8
	Sequence conflict	248	1	V → Y AA sequence Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform Vascular [UniParc]. Last modified October 1, 1996. Version 1. Checksum: BAD87D2499649159	FASTA	510	57,965
	10 20 30 40 50 60 MEDTKESNVK TFCSKNILAI LGFSSIIAVI ALLAVGLTQN KALPENVKYG IVLDAGSSHT 70 80 90 100 110 120 SLYIYKWPAE KENDTGVVHQ VEECRVKGPG ISKFVQKVNE IGIYLTDCME RAREVIPRSQ 130 140 150 160 170 180 HQETPVYLGA TAGMRLLRME SEELADRVLD VVERSLSNYP FDFQGARIIT GQEEGAYGWI 190 200 210 220 230 240 TINYLLGKFS QKTRWFSIVP YETNNQETFG ALDLGGASTQ VTFVPQNQTI ESPDNALQFR 250 260 270 280 290 300 LYGKDYNVYT HSFLCYGKDQ ALWQKLAKDI QVASNEILRD PCFHPGYKKV VNVSDLYKTP 310 320 330 340 350 360 CTKRFEMTLP FQQFEIQGIG NYQQCHQSIL ELFNTSYCPY SQCAFNGIFL PPLQGDFGAF 370 380 390 400 410 420 SAFYFVMKFL NLTSEKVSQE KVTEMMKKFC AQPWEEIKTS YAGVKEKYLS EYCFSGTYIL 430 440 450 460 470 480 SLLLQGYHFT ADSWEHIHFI GKIQGSDAGW TLGYMLNLTN MIPAEQPLST PLSHSTYVFL 490 500 510 MVLFSLVLFT VAIIGLLIFH KPSYFWKDMV
	Isoform Placental I [UniParc]. Checksum: 3E6C59E474010921	FASTA	517	58,706
	10 20 30 40 50 60 MKGTKDLTSQ QKESNVKTFC SKNILAILGF SSIIAVIALL AVGLTQNKAL PENVKYGIVL 70 80 90 100 110 120 DAGSSHTSLY IYKWPAEKEN DTGVVHQVEE CRVKGPGISK FVQKVNEIGI YLTDCMERAR 130 140 150 160 170 180 EVIPRSQHQE TPVYLGATAG MRLLRMESEE LADRVLDVVE RSLSNYPFDF QGARIITGQE 190 200 210 220 230 240 EGAYGWITIN YLLGKFSQKT RWFSIVPYET NNQETFGALD LGGASTQVTF VPQNQTIESP 250 260 270 280 290 300 DNALQFRLYG KDYNVYTHSF LCYGKDQALW QKLAKDIQVA SNEILRDPCF HPGYKKVVNV 310 320 330 340 350 360 SDLYKTPCTK RFEMTLPFQQ FEIQGIGNYQ QCHQSILELF NTSYCPYSQC AFNGIFLPPL 370 380 390 400 410 420 QGDFGAFSAF YFVMKFLNLT SEKVSQEKVT EMMKKFCAQP WEEIKTSYAG VKEKYLSEYC 430 440 450 460 470 480 FSGTYILSLL LQGYHFTADS WEHIHFIGKI QGSDAGWTLG YMLNLTNMIP AEQPLSTPLS 490 500 510 HSTYVFLMVL FSLVLFTVAI IGLLIFHKPS YFWKDMV
	Isoform Placental II [UniParc]. Checksum: E0D3B642D3A5A6C8	FASTA	306	34,175
	10 20 30 40 50 60 MKGTKDLTSQ QKESNVKTFC SKNILAILGF SSIIAVIALL AVGLTQNKAL PENVKYGIVL 70 80 90 100 110 120 DAGSSHTSLY IYKWPAEKEN DTGVVHQVEE CRVKGPGISK FVQKVNEIGI YLTDCMERAR 130 140 150 160 170 180 EVIPRSQHQE TPVYLGATAG MRLLRMESEE LADRVLDVVE RSLSNYPFDF QGARIITGQE 190 200 210 220 230 240 EGAYGWITIN YLLGKFSQKT RWFSIVPYET NNQETFGALD LGGASTQVTF VPQNQTIESP 250 260 270 280 290 300 DNALQFRLYG KDYNVYTHSF LCYGKDQALW QKLAKDIQAS ITQSRPAPFT SAPPAPTSCC FLFQIQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The CD39 lymphoid cell activation antigen. Molecular cloning and structural characterization." Maliszewski C.R., Delespesse G.J.T., Schoenborn M.A., Armitage R.J., Fanslow W.C., Nakajima T., Baker E., Sutherland G.R., Poindexter K., Birks C., Alpert A., Friend D., Gimpel S.D., Gayle R.B. III J. Immunol. 153:3574-3583(1994) [PubMed: 7930580] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VASCULAR).
[2]	"Loss of ATP diphosphohydrolase activity with endothelial cell activation." Robson S.C., Kaczmarek E., Siegel J.B., Candinas D., Koziak K., Millan M., Hancock W.W., Bach F.H. J. Exp. Med. 185:153-163(1997) [PubMed: 8996251] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM VASCULAR). Tissue: Umbilical vein.
[3]	"The cDNA cloning of human placental ecto-ATP diphosphohydrolases I and II." Matsumoto M., Sakurai Y., Kokubo T., Yagi H., Makita K., Matsui T., Titani K., Fujimura Y., Narita N. FEBS Lett. 453:335-340(1999) [PubMed: 10405171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PLACENTAL I AND PLACENTAL II). Tissue: Placenta.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM VASCULAR). Tissue: Trachea.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"Purification and properties of human placental ATP diphosphohydrolase." Christoforidis S., Papamarcaki T., Galaris D., Kellner R., Tsolas O. Eur. J. Biochem. 234:66-74(1995) [PubMed: 8529670] [Abstract] Cited for: PROTEIN SEQUENCE OF 240-242; 162-166; 185-189; 210-223; 243-249 AND 288-297. Tissue: Placenta.
[8]	"Placental ecto-ATP diphosphohydrolase: its structural feature distinct from CD39, localization and inhibition on shear-induced platelet aggregation." Makita K., Shimoyama T., Sakurai Y., Yagi H., Matsumoto M., Narita N., Sakamoto Y., Saito S., Ikeda Y., Suzuki M., Titani K., Fujimura Y. Int. J. Hematol. 68:297-310(1998) [PubMed: 9846014] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-30; 49-65; 94-97; 88-93; 193-223; 245-265; 382-385 AND 399-405 (ISOFORM PLACENTAL I). Tissue: Placenta.
[9]	"Identification and characterization of CD39/vascular ATP diphosphohydrolase." Kaczmarek E., Koziak K., Sevigny J., Siegel J.B., Anrather J., Beaudoin A.R., Bach F.H., Robson S.C. J. Biol. Chem. 271:33116-33122(1996) [PubMed: 8955160] [Abstract] Cited for: FUNCTION.
[10]	"CD39 is an ecto-(Ca2+,Mg2+)-apyrase." Wang T.F., Guidotti G. J. Biol. Chem. 271:9898-9901(1996) [PubMed: 8626624] [Abstract] Cited for: CHARACTERIZATION.
[11]	"Palmitoylation targets CD39/endothelial ATP diphosphohydrolase to caveolae." Koziak K., Kaczmarek E., Kittel A., Sevigny J., Blusztajn J.K., Schulte Am Esch J. II, Imai M., Guckelberger O., Goepfert C., Qawi I., Robson S.C. J. Biol. Chem. 275:2057-2062(2000) [PubMed: 10636909] [Abstract] Cited for: PALMITOYLATION AT CYS-13.
[12]	"Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling." Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A., Lottspeich F., Chen Z. EMBO J. 25:5058-5070(2006) [PubMed: 17053785] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-49 AND TYR-65, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[13]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-73 AND ASN-292, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S73813 mRNA. Translation: AAB32152.1. U87967 mRNA. Translation: AAB47572.1. AJ133133 mRNA. Translation: CAB41886.1. AJ133134 mRNA. Translation: CAB41887.1. AK304018 mRNA. Translation: BAG64933.1. 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.
IPI	IPI00220852. IPI00220853. IPI00382672.
PIR	I56242.
RefSeq	NP_001091645.1. NM_001098175.1. NP_001157650.1. NM_001164178.1. NP_001157653.1. NM_001164181.1. NP_001767.3. NM_001776.5.
UniGene	Hs.576612.
3D structure databases
ProteinModelPortal	P49961.
SMR	P49961. Positions 45-474.
ModBase	Search...
Protein-protein interaction databases
STRING	P49961.
PTM databases
PhosphoSite	P49961.
Polymorphism databases
DMDM	1705710.
Proteomic databases
PRIDE	P49961.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371205; ENSP00000360248; ENSG00000138185.
GeneID	953.
KEGG	hsa:953.
UCSC	uc001klh.2. human.
Organism-specific databases
CTD	953.
GeneCards	GC10P097505.
HGNC	HGNC:3363. ENTPD1.
HPA	CAB002494. HPA014067.
MIM	601752. gene.
neXtProt	NX_P49961.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14506.
HOVERGEN	HBG018982.
OMA	FNTSYCP.
PhylomeDB	P49961.
Gene expression databases
ArrayExpress	P49961.
Bgee	P49961.
CleanEx	HS_ENTPD1.
Genevestigator	P49961.
GermOnline	ENSG00000138185. Homo sapiens.
Family and domain databases
InterPro	IPR000407. GDA1_CD39_NTPase. [Graphical view]
KO	K01510.
PANTHER	PTHR11782. GDA1_CD39_NTPase. 1 hit.
Pfam	PF01150. GDA1_CD39. 1 hit. [Graphical view]
PROSITE	PS01238. GDA1_CD39_NTPASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	3966.
SOURCE	Search...

Entry information

Entry name

ENTP1_HUMAN

Accession

Primary (citable) accession number: P49961
Secondary accession number(s): A9Z1X8 , B4E1X1, Q5T561, Q5T562, Q9UQQ9, Q9Y3Q9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 115 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.