ENTP2_HUMAN
ID ENTP2_HUMAN Reviewed; 495 AA.
AC Q9Y5L3; O15464; Q5SPY6; Q5SPY7;
DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Ectonucleoside triphosphate diphosphohydrolase 2;
DE Short=NTPDase 2;
DE EC=3.6.1.-;
DE AltName: Full=CD39 antigen-like 1;
DE AltName: Full=Ecto-ATP diphosphohydrolase 2;
DE Short=Ecto-ATPDase 2;
DE Short=Ecto-ATPase 2;
GN Name=ENTPD2; Synonyms=CD39L1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RC TISSUE=Keratinocyte;
RX PubMed=9271669; DOI=10.1007/s003359900534;
RA Chadwick B.P., Frischauf A.-M.;
RT "Cloning and mapping of a human and mouse gene with homology to ecto-ATPase
RT genes.";
RL Mamm. Genome 8:668-672(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), CATALYTIC ACTIVITY, COFACTOR,
RP AND CHARACTERIZATION.
RX PubMed=10510450; DOI=10.1038/sj.bjp.0702805;
RA Mateo J., Harden T.K., Boyer J.L.;
RT "Functional expression of a cDNA encoding a human ecto-ATPase.";
RL Br. J. Pharmacol. 128:396-402(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RX PubMed=16101300; DOI=10.1021/bi050019k;
RA Mukasa T., Lee Y., Knowles A.F.;
RT "Either the carboxyl- or the amino-terminal region of the human ecto-ATPase
RT (E-NTPDase 2) confers detergent and temperature sensitivity to the chicken
RT ecto-ATP-diphosphohydrolase (E-NTPDase 8).";
RL Biochemistry 44:11160-11170(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, MUTAGENESIS OF CYS-399 AND
RP ASN-443, AND GLYCOSYLATION AT ASN-443.
RX PubMed=12888562; DOI=10.1074/jbc.m307854200;
RA Mateo J., Kreda S., Henry C.E., Harden T.K., Boyer J.L.;
RT "Requirement of Cys399 for processing of the human ecto-ATPase (NTPDase2)
RT and its implications for determination of the activities of splice variants
RT of the enzyme.";
RL J. Biol. Chem. 278:39960-39968(2003).
CC -!- FUNCTION: In the nervous system, could hydrolyze ATP and other
CC nucleotides to regulate purinergic neurotransmission. Hydrolyzes ADP
CC only to a marginal extent. The order of activity with different
CC substrates is ATP > GTP > CTP = ITP > UTP >> ADP = UDP.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:10510450};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10510450};
CC -!- INTERACTION:
CC Q9Y5L3; P42858: HTT; NbExp=3; IntAct=EBI-3913907, EBI-466029;
CC Q9Y5L3; Q96CV9: OPTN; NbExp=3; IntAct=EBI-3913907, EBI-748974;
CC -!- SUBCELLULAR LOCATION: [Isoform Long]: Cell membrane; Multi-pass
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform Short]: Endoplasmic reticulum membrane;
CC Multi-pass membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform gamma]: Endoplasmic reticulum membrane;
CC Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Long; Synonyms=alpha;
CC IsoId=Q9Y5L3-1; Sequence=Displayed;
CC Name=Short; Synonyms=beta;
CC IsoId=Q9Y5L3-2; Sequence=VSP_003610;
CC Name=gamma;
CC IsoId=Q9Y5L3-3; Sequence=VSP_003610, VSP_053548;
CC -!- TISSUE SPECIFICITY: Brain, placenta, skeletal muscle, kidney, pancreas,
CC heart, ovary, testis, colon, small intestine, prostate and pancreas. No
CC expression in adult thymus, spleen, lung, liver and peripheral blood
CC leukocytes.
CC -!- MISCELLANEOUS: [Isoform Short]: Catalytically inactive. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform gamma]: Catalytically inactive. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the GDA1/CD39 NTPase family. {ECO:0000305}.
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DR EMBL; U91510; AAB81013.1; -; mRNA.
DR EMBL; AF144748; AAD40239.1; -; mRNA.
DR EMBL; EF495152; ABP58644.1; -; mRNA.
DR EMBL; AL807752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW88336.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW88337.1; -; Genomic_DNA.
DR EMBL; BC035738; AAH35738.1; -; mRNA.
DR CCDS; CCDS7025.1; -. [Q9Y5L3-2]
DR CCDS; CCDS7026.1; -. [Q9Y5L3-1]
DR RefSeq; NP_001237.1; NM_001246.3. [Q9Y5L3-2]
DR RefSeq; NP_982293.1; NM_203468.2. [Q9Y5L3-1]
DR AlphaFoldDB; Q9Y5L3; -.
DR SMR; Q9Y5L3; -.
DR BioGRID; 107392; 140.
DR IntAct; Q9Y5L3; 3.
DR STRING; 9606.ENSP00000347213; -.
DR BindingDB; Q9Y5L3; -.
DR ChEMBL; CHEMBL5049; -.
DR GuidetoPHARMACOLOGY; 2889; -.
DR GlyConnect; 1193; 45 N-Linked glycans (5 sites).
DR GlyGen; Q9Y5L3; 5 sites, 47 N-linked glycans (5 sites).
DR iPTMnet; Q9Y5L3; -.
DR PhosphoSitePlus; Q9Y5L3; -.
DR BioMuta; ENTPD2; -.
DR DMDM; 18203633; -.
DR CPTAC; CPTAC-1489; -.
DR EPD; Q9Y5L3; -.
DR jPOST; Q9Y5L3; -.
DR MassIVE; Q9Y5L3; -.
DR MaxQB; Q9Y5L3; -.
DR PaxDb; Q9Y5L3; -.
DR PeptideAtlas; Q9Y5L3; -.
DR PRIDE; Q9Y5L3; -.
DR ProteomicsDB; 86440; -. [Q9Y5L3-1]
DR ProteomicsDB; 86441; -. [Q9Y5L3-2]
DR Antibodypedia; 2981; 220 antibodies from 32 providers.
DR DNASU; 954; -.
DR Ensembl; ENST00000312665.7; ENSP00000312494.5; ENSG00000054179.12. [Q9Y5L3-2]
DR Ensembl; ENST00000355097.7; ENSP00000347213.2; ENSG00000054179.12. [Q9Y5L3-1]
DR GeneID; 954; -.
DR KEGG; hsa:954; -.
DR MANE-Select; ENST00000355097.7; ENSP00000347213.2; NM_203468.3; NP_982293.1.
DR UCSC; uc004ckw.3; human. [Q9Y5L3-1]
DR CTD; 954; -.
DR DisGeNET; 954; -.
DR GeneCards; ENTPD2; -.
DR HGNC; HGNC:3364; ENTPD2.
DR HPA; ENSG00000054179; Tissue enhanced (brain).
DR MIM; 602012; gene.
DR neXtProt; NX_Q9Y5L3; -.
DR OpenTargets; ENSG00000054179; -.
DR PharmGKB; PA27799; -.
DR VEuPathDB; HostDB:ENSG00000054179; -.
DR eggNOG; KOG1386; Eukaryota.
DR GeneTree; ENSGT01050000244835; -.
DR HOGENOM; CLU_010246_2_3_1; -.
DR InParanoid; Q9Y5L3; -.
DR OMA; QTWAELQ; -.
DR OrthoDB; 231215at2759; -.
DR PhylomeDB; Q9Y5L3; -.
DR TreeFam; TF332859; -.
DR BioCyc; MetaCyc:ENSG00000054179-MON; -.
DR BRENDA; 3.6.1.5; 2681.
DR PathwayCommons; Q9Y5L3; -.
DR Reactome; R-HSA-8850843; Phosphate bond hydrolysis by NTPDase proteins.
DR SABIO-RK; Q9Y5L3; -.
DR SignaLink; Q9Y5L3; -.
DR BioGRID-ORCS; 954; 15 hits in 1062 CRISPR screens.
DR ChiTaRS; ENTPD2; human.
DR GeneWiki; ENTPD2; -.
DR GenomeRNAi; 954; -.
DR Pharos; Q9Y5L3; Tchem.
DR PRO; PR:Q9Y5L3; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9Y5L3; protein.
DR Bgee; ENSG00000054179; Expressed in dorsal root ganglion and 127 other tissues.
DR Genevisible; Q9Y5L3; HS.
DR GO; GO:0005604; C:basement membrane; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004382; F:guanosine-diphosphatase activity; IBA:GO_Central.
DR GO; GO:0017110; F:nucleoside-diphosphatase activity; IBA:GO_Central.
DR GO; GO:0017111; F:nucleoside-triphosphatase activity; IEA:Ensembl.
DR GO; GO:0045134; F:uridine-diphosphatase activity; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0009134; P:nucleoside diphosphate catabolic process; IBA:GO_Central.
DR GO; GO:0030168; P:platelet activation; IEA:Ensembl.
DR GO; GO:0009181; P:purine ribonucleoside diphosphate catabolic process; IEA:Ensembl.
DR InterPro; IPR000407; GDA1_CD39_NTPase.
DR PANTHER; PTHR11782; PTHR11782; 1.
DR Pfam; PF01150; GDA1_CD39; 1.
DR PROSITE; PS01238; GDA1_CD39_NTPASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Calcium; Cell membrane; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Magnesium; Membrane;
KW Nucleotide-binding; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..495
FT /note="Ectonucleoside triphosphate diphosphohydrolase 2"
FT /id="PRO_0000209906"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..462
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 463..483
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 484..495
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 165
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O35795"
FT BINDING 204..208
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35795"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 129
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 378
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 443
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12888562"
FT DISULFID 75..99
FT /evidence="ECO:0000250|UniProtKB:O35795"
FT DISULFID 242..284
FT /evidence="ECO:0000250|UniProtKB:O35795"
FT DISULFID 265..310
FT /evidence="ECO:0000250|UniProtKB:O35795"
FT DISULFID 323..328
FT /evidence="ECO:0000250|UniProtKB:O35795"
FT DISULFID 377..399
FT /evidence="ECO:0000250|UniProtKB:O35795"
FT VAR_SEQ 383..405
FT /note="Missing (in isoform Short and isoform gamma)"
FT /evidence="ECO:0000303|PubMed:9271669"
FT /id="VSP_003610"
FT VAR_SEQ 406..428
FT /note="Missing (in isoform gamma)"
FT /evidence="ECO:0000305"
FT /id="VSP_053548"
FT VARIANT 103
FT /note="A -> V (in dbSNP:rs34618694)"
FT /id="VAR_050307"
FT MUTAGEN 399
FT /note="C->S: Abolishes ecto-ATPase activity, accumulates
FT intracellularly."
FT /evidence="ECO:0000269|PubMed:12888562"
FT MUTAGEN 443
FT /note="N->D: 7% of wild-type ATPase activity, accumulates
FT intracellularly."
FT /evidence="ECO:0000269|PubMed:12888562"
SQ SEQUENCE 495 AA; 53665 MW; 3BDBA114A679B422 CRC64;
MAGKVRSLLP PLLLAAAGLA GLLLLCVPTR DVREPPALKY GIVLDAGSSH TSMFIYKWPA
DKENDTGIVG QHSSCDVPGG GISSYADNPS GASQSLVGCL EQALQDVPKE RHAGTPLYLG
ATAGMRLLNL TNPEASTSVL MAVTHTLTQY PFDFRGARIL SGQEEGVFGW VTANYLLENF
IKYGWVGRWF RPRKGTLGAM DLGGASTQIT FETTSPAEDR ASEVQLHLYG QHYRVYTHSF
LCYGRDQVLQ RLLASALQTH GFHPCWPRGF STQVLLGDVY QSPCTMAQRP QNFNSSARVS
LSGSSDPHLC RDLVSGLFSF SSCPFSRCSF NGVFQPPVAG NFVAFSAFFY TVDFLRTSMG
LPVATLQQLE AAAVNVCNQT WAQLQARVPG QRARLADYCA GAMFVQQLLS RGYGFDERAF
GGVIFQKKAA DTAVGWALGY MLNLTNLIPA DPPGLRKGTD FSSWVVLLLL FASALLAALV
LLLRQVHSAK LPSTI
