ID ENTP8_HUMAN Reviewed; 495 AA.
AC Q5MY95; A2BG17; Q6UVZ0;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 2.
DT 27-MAR-2024, entry version 150.
DE RecName: Full=Ectonucleoside triphosphate diphosphohydrolase 8;
DE Short=E-NTPDase 8;
DE Short=NTPDase 8;
DE Short=NTPDase8;
DE EC=3.6.1.5;
GN Name=ENTPD8; ORFNames=UNQ2492/PRO5779;
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 1), FUNCTION, ENZYME ACTIVITY, DOMAIN,
RP GLYCOSYLATION, AND VARIANT PRO-62.
RX PubMed=16752921; DOI=10.1021/bi052268e;
RA Knowles A.F., Li C.;
RT "Molecular cloning and characterization of expressed human ecto-nucleoside
RT triphosphate diphosphohydrolase 8 (E-NTPDase 8) and its soluble
RT extracellular domain.";
RL Biochemistry 45:7323-7333(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND VARIANT PRO-62.
RC TISSUE=Liver;
RX PubMed=17095758; DOI=10.1152/ajpgi.00293.2006;
RA Fausther M., Lecka J., Kukulski F., Levesque S.A., Pelletier J.,
RA Zimmermann H., Dranoff J.A., Sevigny J.;
RT "Cloning, purification, and identification of the liver canalicular ecto-
RT ATPase as NTPDase8.";
RL Am. J. Physiol. 292:G785-G795(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT PRO-62.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
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 MRNA] (ISOFORM 2), AND VARIANT PRO-62.
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 [6]
RP ACTIVITY REGULATION.
RX PubMed=17603550; DOI=10.1038/sj.bjp.0707361;
RA Levesque S.A., Lavoie E.G., Lecka J., Bigonnesse F., Sevigny J.;
RT "Specificity of the ecto-ATPase inhibitor ARL 67156 on human and mouse
RT ectonucleotidases.";
RL Br. J. Pharmacol. 152:141-150(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Canalicular ectonucleoside NTPDase responsible for the main
CC hepatic NTPDase activity. Ectonucleoside NTPDases catalyze the
CC hydrolysis of gamma- and beta-phosphate residues of nucleotides,
CC playing a central role in concentration of extracellular nucleotides.
CC Has activity toward ATP, ADP, UTP and UDP, but not toward AMP.
CC {ECO:0000269|PubMed:16752921, ECO:0000269|PubMed:17095758}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + 2 H2O = a ribonucleoside
CC 5'-phosphate + 2 H(+) + 2 phosphate; Xref=Rhea:RHEA:36795,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58043, ChEBI:CHEBI:61557; EC=3.6.1.5;
CC Evidence={ECO:0000269|PubMed:16752921, ECO:0000269|PubMed:17095758};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Ca(2+) or Mg(2+). Has lower efficiency with Mg(2+). {ECO:0000250};
CC -!- ACTIVITY REGULATION: Not inhibited by ARL 67156.
CC {ECO:0000269|PubMed:17603550}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=81 uM for ATP {ECO:0000269|PubMed:17095758};
CC KM=137 uM for ADP {ECO:0000269|PubMed:17095758};
CC KM=480 uM for UTP {ECO:0000269|PubMed:17095758};
CC KM=241 uM for UDP {ECO:0000269|PubMed:17095758};
CC Vmax=790 nmol/min/mg enzyme with ATP as substrate
CC {ECO:0000269|PubMed:17095758};
CC Vmax=163 nmol/min/mg enzyme with ADP as substrate
CC {ECO:0000269|PubMed:17095758};
CC Vmax=1100 nmol/min/mg enzyme with UTP as substrate
CC {ECO:0000269|PubMed:17095758};
CC Vmax=110 nmol/min/mg enzyme with UDP as substrate
CC {ECO:0000269|PubMed:17095758};
CC -!- INTERACTION:
CC Q5MY95-2; Q9UHP7-3: CLEC2D; NbExp=3; IntAct=EBI-12909060, EBI-11749983;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5MY95-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5MY95-2; Sequence=VSP_028559;
CC -!- DOMAIN: The transmembranous domains are involved in regulation of
CC enzyme activity. {ECO:0000269|PubMed:16752921}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16752921}.
CC -!- SIMILARITY: Belongs to the GDA1/CD39 NTPase family. {ECO:0000305}.
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DR EMBL; AY903953; AAW83515.1; -; Transcribed_RNA.
DR EMBL; AY903954; AAW83516.1; -; mRNA.
DR EMBL; AY430414; AAR04374.1; -; mRNA.
DR EMBL; AY359088; AAQ89446.1; -; mRNA.
DR EMBL; BX322799; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC141810; AAI41811.1; -; mRNA.
DR CCDS; CCDS43913.1; -. [Q5MY95-1]
DR CCDS; CCDS7043.1; -. [Q5MY95-2]
DR RefSeq; NP_001028285.1; NM_001033113.1. [Q5MY95-1]
DR RefSeq; NP_940987.2; NM_198585.2. [Q5MY95-2]
DR AlphaFoldDB; Q5MY95; -.
DR SMR; Q5MY95; -.
DR BioGRID; 132022; 4.
DR IntAct; Q5MY95; 1.
DR STRING; 9606.ENSP00000360561; -.
DR BindingDB; Q5MY95; -.
DR ChEMBL; CHEMBL5338; -.
DR GlyCosmos; Q5MY95; 3 sites, No reported glycans.
DR GlyGen; Q5MY95; 3 sites.
DR iPTMnet; Q5MY95; -.
DR PhosphoSitePlus; Q5MY95; -.
DR BioMuta; ENTPD8; -.
DR DMDM; 158705943; -.
DR EPD; Q5MY95; -.
DR jPOST; Q5MY95; -.
DR MassIVE; Q5MY95; -.
DR PaxDb; 9606-ENSP00000360561; -.
DR PeptideAtlas; Q5MY95; -.
DR ProteomicsDB; 63592; -. [Q5MY95-1]
DR ProteomicsDB; 63593; -. [Q5MY95-2]
DR Antibodypedia; 19016; 174 antibodies from 20 providers.
DR DNASU; 377841; -.
DR Ensembl; ENST00000344119.6; ENSP00000344089.2; ENSG00000188833.10. [Q5MY95-2]
DR Ensembl; ENST00000371506.7; ENSP00000360561.2; ENSG00000188833.10. [Q5MY95-1]
DR GeneID; 377841; -.
DR KEGG; hsa:377841; -.
DR MANE-Select; ENST00000371506.7; ENSP00000360561.2; NM_001033113.2; NP_001028285.1.
DR UCSC; uc004cmw.3; human. [Q5MY95-1]
DR AGR; HGNC:24860; -.
DR CTD; 377841; -.
DR DisGeNET; 377841; -.
DR GeneCards; ENTPD8; -.
DR HGNC; HGNC:24860; ENTPD8.
DR HPA; ENSG00000188833; Tissue enhanced (intestine, liver, stomach).
DR MIM; 616748; gene.
DR neXtProt; NX_Q5MY95; -.
DR OpenTargets; ENSG00000188833; -.
DR PharmGKB; PA142671906; -.
DR VEuPathDB; HostDB:ENSG00000188833; -.
DR eggNOG; KOG1386; Eukaryota.
DR GeneTree; ENSGT01100000263542; -.
DR HOGENOM; CLU_010246_2_3_1; -.
DR InParanoid; Q5MY95; -.
DR OMA; TVNTTIW; -.
DR OrthoDB; 180318at2759; -.
DR PhylomeDB; Q5MY95; -.
DR TreeFam; TF332859; -.
DR BRENDA; 3.6.1.5; 2681.
DR PathwayCommons; Q5MY95; -.
DR Reactome; R-HSA-8850843; Phosphate bond hydrolysis by NTPDase proteins.
DR SABIO-RK; Q5MY95; -.
DR SignaLink; Q5MY95; -.
DR BioGRID-ORCS; 377841; 13 hits in 1149 CRISPR screens.
DR GenomeRNAi; 377841; -.
DR Pharos; Q5MY95; Tbio.
DR PRO; PR:Q5MY95; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q5MY95; Protein.
DR Bgee; ENSG00000188833; Expressed in mucosa of transverse colon and 69 other cell types or tissues.
DR ExpressionAtlas; Q5MY95; baseline and differential.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004050; F:apyrase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004382; F:GDP phosphatase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017111; F:ribonucleoside triphosphate phosphatase activity; IEA:Ensembl.
DR GO; GO:0045134; F:UDP phosphatase activity; IBA:GO_Central.
DR GO; GO:0009133; P:nucleoside diphosphate biosynthetic process; IEA:Ensembl.
DR GO; GO:0009134; P:nucleoside diphosphate catabolic process; IBA:GO_Central.
DR GO; GO:0009124; P:nucleoside monophosphate biosynthetic process; IEA:Ensembl.
DR CDD; cd00012; NBD_sugar-kinase_HSP70_actin; 1.
DR Gene3D; 3.30.420.40; -; 1.
DR Gene3D; 3.30.420.150; Exopolyphosphatase. Domain 2; 1.
DR InterPro; IPR000407; GDA1_CD39_NTPase.
DR PANTHER; PTHR11782; ADENOSINE/GUANOSINE DIPHOSPHATASE; 1.
DR PANTHER; PTHR11782:SF31; ECTONUCLEOSIDE TRIPHOSPHATE DIPHOSPHOHYDROLASE 8; 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 Glycoprotein; Hydrolase; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..495
FT /note="Ectonucleoside triphosphate diphosphohydrolase 8"
FT /id="PRO_0000306882"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..471
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 472..492
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 493..495
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 168
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O35795"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 304
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 363
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 78..102
FT /evidence="ECO:0000250"
FT DISULFID 246..292
FT /evidence="ECO:0000250"
FT DISULFID 329..335
FT /evidence="ECO:0000250"
FT DISULFID 381..403
FT /evidence="ECO:0000250"
FT VAR_SEQ 351..387
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_028559"
FT VARIANT 62
FT /note="L -> P (in dbSNP:rs6606582)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16752921,
FT ECO:0000269|PubMed:17095758"
FT /id="VAR_035339"
FT VARIANT 428
FT /note="E -> K (in dbSNP:rs61491031)"
FT /id="VAR_061385"
SQ SEQUENCE 495 AA; 53904 MW; 030200E15F662D82 CRC64;
MGLSRKEQVF LALLGASGVS GLTALILLLV EATSVLLPTD IKFGIVFDAG SSHTSLFLYQ
WLANKENGTG VVSQALACQV EGPGISSYTS NAAQAGESLQ GCLEEALVLI PEAQHRKTPT
FLGATAGMRL LSRKNSSQAR DIFAAVTQVL GRSPVDFWGA ELLAGQAEGA FGWITVNYGL
GTLVKYSFTG EWIQPPEEML VGALDMGGAS TQITFVPGGP ILDKSTQADF RLYGSDYSVY
THSYLCFGRD QMLSRLLVGL VQSRPAALLR HPCYLSGYQT TLALGPLYES PCVHATPPLS
LPQNLTVEGT GNPGACVSAI RELFNFSSCQ GQEDCAFDGV YQPPLRGQFY AFSNFYYTFH
FLNLTSRQPL STVNATIWEF CQRPWKLVEA SYPGQDRWLR DYCASGLYIL TLLHEGYGFS
EETWPSLEFR KQAGGVDIGW TLGYMLNLTG MIPADAPAQW RAESYGVWVA KVVFMVLALV
AVVGAALVQL FWLQD
//
