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Protein

Ectonucleoside triphosphate diphosphohydrolase 8

Gene

ENTPD8

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

Functioni

Canalicular ectonucleoside NTPDase responsible for the main hepatic NTPDase activity. Ectonucleoside NTPDases catalyze the hydrolysis of gamma- and beta-phosphate residues of nucleotides, playing a central role in concentration of extracellular nucleotides. Has activity toward ATP, ADP, UTP and UDP, but not toward AMP.2 Publications

Catalytic activityi

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

Cofactori

Ca2+By similarity, Mg2+By similarityNote: Ca(2+) or Mg(2+). Has lower efficiency with Mg2+.By similarity

Enzyme regulationi

Not inhibited by ARL 67156.1 Publication

Kineticsi

  1. KM=81 µM for ATP1 Publication
  2. KM=137 µM for ADP1 Publication
  3. KM=480 µM for UTP1 Publication
  4. KM=241 µM for UDP1 Publication
  1. Vmax=790 nmol/min/mg enzyme with ATP as substrate1 Publication
  2. Vmax=163 nmol/min/mg enzyme with ADP as substrate1 Publication
  3. Vmax=1100 nmol/min/mg enzyme with UTP as substrate1 Publication
  4. Vmax=110 nmol/min/mg enzyme with UDP as substrate1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei168 – 1681Proton acceptorBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

ATP-binding, Calcium, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

SABIO-RKQ5MY95.

Names & Taxonomyi

Protein namesi
Recommended name:
Ectonucleoside triphosphate diphosphohydrolase 8 (EC:3.6.1.5)
Short name:
E-NTPDase 8
Short name:
NTPDase 8
Short name:
NTPDase8
Gene namesi
Name:ENTPD8
ORF Names:UNQ2492/PRO5779
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:24860. ENTPD8.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 88CytoplasmicSequence Analysis
Transmembranei9 – 2921HelicalSequence AnalysisAdd
BLAST
Topological domaini30 – 471442ExtracellularSequence AnalysisAdd
BLAST
Transmembranei472 – 49221HelicalSequence AnalysisAdd
BLAST
Topological domaini493 – 4953CytoplasmicSequence Analysis

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142671906.

Polymorphism and mutation databases

BioMutaiENTPD8.
DMDMi158705943.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 495495Ectonucleoside triphosphate diphosphohydrolase 8PRO_0000306882Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi67 – 671N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi78 ↔ 102By similarity
Disulfide bondi246 ↔ 292By similarity
Glycosylationi304 – 3041N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi329 ↔ 335By similarity
Glycosylationi363 – 3631N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi381 ↔ 403By similarity

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ5MY95.
PRIDEiQ5MY95.

PTM databases

PhosphoSiteiQ5MY95.

Expressioni

Gene expression databases

BgeeiQ5MY95.
CleanExiHS_ENTPD8.
ExpressionAtlasiQ5MY95. baseline.
GenevestigatoriQ5MY95.

Organism-specific databases

HPAiHPA021509.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000360561.

Structurei

3D structure databases

ProteinModelPortaliQ5MY95.
SMRiQ5MY95. Positions 41-458.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The transmembranous domains are involved in regulation of enzyme activity.1 Publication

Sequence similaritiesi

Belongs to the GDA1/CD39 NTPase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG5371.
GeneTreeiENSGT00550000074435.
HOGENOMiHOG000059572.
HOVERGENiHBG018982.
InParanoidiQ5MY95.
KOiK01510.
OMAiVDFWGAE.
OrthoDBiEOG754HPX.
PhylomeDBiQ5MY95.
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5MY95-1) [UniParc]FASTAAdd to basket

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
MGLSRKEQVF LALLGASGVS GLTALILLLV EATSVLLPTD IKFGIVFDAG
60 70 80 90 100
SSHTSLFLYQ WLANKENGTG VVSQALACQV EGPGISSYTS NAAQAGESLQ
110 120 130 140 150
GCLEEALVLI PEAQHRKTPT FLGATAGMRL LSRKNSSQAR DIFAAVTQVL
160 170 180 190 200
GRSPVDFWGA ELLAGQAEGA FGWITVNYGL GTLVKYSFTG EWIQPPEEML
210 220 230 240 250
VGALDMGGAS TQITFVPGGP ILDKSTQADF RLYGSDYSVY THSYLCFGRD
260 270 280 290 300
QMLSRLLVGL VQSRPAALLR HPCYLSGYQT TLALGPLYES PCVHATPPLS
310 320 330 340 350
LPQNLTVEGT GNPGACVSAI RELFNFSSCQ GQEDCAFDGV YQPPLRGQFY
360 370 380 390 400
AFSNFYYTFH FLNLTSRQPL STVNATIWEF CQRPWKLVEA SYPGQDRWLR
410 420 430 440 450
DYCASGLYIL TLLHEGYGFS EETWPSLEFR KQAGGVDIGW TLGYMLNLTG
460 470 480 490
MIPADAPAQW RAESYGVWVA KVVFMVLALV AVVGAALVQL FWLQD
Length:495
Mass (Da):53,904
Last modified:October 2, 2007 - v2
Checksum:i030200E15F662D82
GO
Isoform 2 (identifier: Q5MY95-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     351-387: Missing.

Show »
Length:458
Mass (Da):49,393
Checksum:iC2BEDCB65064B6B3
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti62 – 621L → P.4 Publications
Corresponds to variant rs6606582 [ dbSNP | Ensembl ].
VAR_035339
Natural varianti428 – 4281E → K.
Corresponds to variant rs61491031 [ dbSNP | Ensembl ].
VAR_061385

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei351 – 38737Missing in isoform 2. 2 PublicationsVSP_028559Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY903953 Transcribed RNA. Translation: AAW83515.1.
AY903954 mRNA. Translation: AAW83516.1.
AY430414 mRNA. Translation: AAR04374.1.
AY359088 mRNA. Translation: AAQ89446.1.
BX322799 Genomic DNA. Translation: CAM24777.1.
BC141810 mRNA. Translation: AAI41811.1.
CCDSiCCDS43913.1. [Q5MY95-1]
CCDS7043.1. [Q5MY95-2]
RefSeqiNP_001028285.1. NM_001033113.1. [Q5MY95-1]
NP_940987.2. NM_198585.2. [Q5MY95-2]
UniGeneiHs.512562.

Genome annotation databases

EnsembliENST00000344119; ENSP00000344089; ENSG00000188833. [Q5MY95-2]
ENST00000371506; ENSP00000360561; ENSG00000188833. [Q5MY95-1]
ENST00000472938; ENSP00000420531; ENSG00000188833. [Q5MY95-1]
GeneIDi377841.
KEGGihsa:377841.
UCSCiuc004cmw.3. human. [Q5MY95-1]
uc004cmx.3. human. [Q5MY95-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY903953 Transcribed RNA. Translation: AAW83515.1.
AY903954 mRNA. Translation: AAW83516.1.
AY430414 mRNA. Translation: AAR04374.1.
AY359088 mRNA. Translation: AAQ89446.1.
BX322799 Genomic DNA. Translation: CAM24777.1.
BC141810 mRNA. Translation: AAI41811.1.
CCDSiCCDS43913.1. [Q5MY95-1]
CCDS7043.1. [Q5MY95-2]
RefSeqiNP_001028285.1. NM_001033113.1. [Q5MY95-1]
NP_940987.2. NM_198585.2. [Q5MY95-2]
UniGeneiHs.512562.

3D structure databases

ProteinModelPortaliQ5MY95.
SMRiQ5MY95. Positions 41-458.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000360561.

Chemistry

BindingDBiQ5MY95.
ChEMBLiCHEMBL5338.

PTM databases

PhosphoSiteiQ5MY95.

Polymorphism and mutation databases

BioMutaiENTPD8.
DMDMi158705943.

Proteomic databases

PaxDbiQ5MY95.
PRIDEiQ5MY95.

Protocols and materials databases

DNASUi377841.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344119; ENSP00000344089; ENSG00000188833. [Q5MY95-2]
ENST00000371506; ENSP00000360561; ENSG00000188833. [Q5MY95-1]
ENST00000472938; ENSP00000420531; ENSG00000188833. [Q5MY95-1]
GeneIDi377841.
KEGGihsa:377841.
UCSCiuc004cmw.3. human. [Q5MY95-1]
uc004cmx.3. human. [Q5MY95-2]

Organism-specific databases

CTDi377841.
GeneCardsiGC09M140328.
HGNCiHGNC:24860. ENTPD8.
HPAiHPA021509.
neXtProtiNX_Q5MY95.
PharmGKBiPA142671906.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5371.
GeneTreeiENSGT00550000074435.
HOGENOMiHOG000059572.
HOVERGENiHBG018982.
InParanoidiQ5MY95.
KOiK01510.
OMAiVDFWGAE.
OrthoDBiEOG754HPX.
PhylomeDBiQ5MY95.
TreeFamiTF332859.

Enzyme and pathway databases

SABIO-RKQ5MY95.

Miscellaneous databases

GenomeRNAii377841.
NextBioi100687.
PROiQ5MY95.

Gene expression databases

BgeeiQ5MY95.
CleanExiHS_ENTPD8.
ExpressionAtlasiQ5MY95. baseline.
GenevestigatoriQ5MY95.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and characterization of expressed human ecto-nucleoside triphosphate diphosphohydrolase 8 (E-NTPDase 8) and its soluble extracellular domain."
    Knowles A.F., Li C.
    Biochemistry 45:7323-7333(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME ACTIVITY, DOMAIN, GLYCOSYLATION, VARIANT PRO-62.
  2. "Cloning, purification, and identification of the liver canalicular ecto-ATPase as NTPDase8."
    Fausther M., Lecka J., Kukulski F., Levesque S.A., Pelletier J., Zimmermann H., Dranoff J.A., Sevigny J.
    Am. J. Physiol. 292:G785-G795(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, VARIANT PRO-62.
    Tissue: Liver.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT PRO-62.
  4. "DNA sequence and analysis of human chromosome 9."
    Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
    , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
    Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT PRO-62.
  6. "Specificity of the ecto-ATPase inhibitor ARL 67156 on human and mouse ectonucleotidases."
    Levesque S.A., Lavoie E.G., Lecka J., Bigonnesse F., Sevigny J.
    Br. J. Pharmacol. 152:141-150(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION.
  7. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiENTP8_HUMAN
AccessioniPrimary (citable) accession number: Q5MY95
Secondary accession number(s): A2BG17, Q6UVZ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: October 2, 2007
Last modified: May 27, 2015
This is version 92 of the entry and version 2 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, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.