Q5MY95 (ENTP8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ectonucleoside triphosphate diphosphohydrolase 8
Short name=E-NTPDase 8
Short name=NTPDase 8
Short name=NTPDase8
EC=3.6.1.5

Gene names

Name:	ENTPD8
ORF Names:	UNQ2492/PRO5779

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	495 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.2
Catalytic activity	ATP + 2 H2O = AMP + 2 phosphate. Ref.1 Ref.2
Cofactor	Calcium By similarity.
Enzyme regulation	Not inhibited by ARL 67156. Ref.6
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity.
Domain	The transmembranous domains are involved in regulation of enzyme activity. Ref.1
Post-translational modification	N-glycosylated. Ref.1
Sequence similarities	Belongs to the GDA1/CD39 NTPase family.
Biophysicochemical properties	Kinetic parameters: KM=81 µM for ATP Ref.2 KM=137 µM for ADP KM=480 µM for UTP KM=241 µM for UDP Vmax=790 nmol/min/mg enzyme with ATP as substrate Vmax=163 nmol/min/mg enzyme with ADP as substrate Vmax=1100 nmol/min/mg enzyme with UTP as substrate Vmax=110 nmol/min/mg enzyme with UDP as substrate

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Calcium Nucleotide-binding
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q5MY95-1)

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 2 (identifier: Q5MY95-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 495	495	Ectonucleoside triphosphate diphosphohydrolase 8		PRO_0000306882
Regions
	Topological domain	1 – 8	8	Cytoplasmic Potential
	Transmembrane	9 – 29	21	Helical; Potential
	Topological domain	30 – 471	442	Extracellular Potential
	Transmembrane	472 – 492	21	Helical; Potential
	Topological domain	493 – 495	3	Cytoplasmic Potential
Sites
	Active site	168	1	Proton acceptor By similarity
Amino acid modifications
	Glycosylation	67	1	N-linked (GlcNAc...) Potential
	Glycosylation	304	1	N-linked (GlcNAc...) Potential
	Glycosylation	363	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	351 – 387	37	Missing in isoform 2.		VSP_028559
	Natural variant	62	1	L → P. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs6606582 [ dbSNP | Ensembl ].		VAR_035339
	Natural variant	428	1	E → K. Corresponds to variant rs61491031 [ dbSNP | Ensembl ].		VAR_061385

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 2, 2007. Version 2. Checksum: 030200E15F662D82	FASTA	495	53,904
	10 20 30 40 50 60 MGLSRKEQVF LALLGASGVS GLTALILLLV EATSVLLPTD IKFGIVFDAG SSHTSLFLYQ 70 80 90 100 110 120 WLANKENGTG VVSQALACQV EGPGISSYTS NAAQAGESLQ GCLEEALVLI PEAQHRKTPT 130 140 150 160 170 180 FLGATAGMRL LSRKNSSQAR DIFAAVTQVL GRSPVDFWGA ELLAGQAEGA FGWITVNYGL 190 200 210 220 230 240 GTLVKYSFTG EWIQPPEEML VGALDMGGAS TQITFVPGGP ILDKSTQADF RLYGSDYSVY 250 260 270 280 290 300 THSYLCFGRD QMLSRLLVGL VQSRPAALLR HPCYLSGYQT TLALGPLYES PCVHATPPLS 310 320 330 340 350 360 LPQNLTVEGT GNPGACVSAI RELFNFSSCQ GQEDCAFDGV YQPPLRGQFY AFSNFYYTFH 370 380 390 400 410 420 FLNLTSRQPL STVNATIWEF CQRPWKLVEA SYPGQDRWLR DYCASGLYIL TLLHEGYGFS 430 440 450 460 470 480 EETWPSLEFR KQAGGVDIGW TLGYMLNLTG MIPADAPAQW RAESYGVWVA KVVFMVLALV 490 AVVGAALVQL FWLQD
	Isoform 2 [UniParc]. Checksum: C2BEDCB65064B6B3	FASTA	458	49,393
	10 20 30 40 50 60 MGLSRKEQVF LALLGASGVS GLTALILLLV EATSVLLPTD IKFGIVFDAG SSHTSLFLYQ 70 80 90 100 110 120 WLANKENGTG VVSQALACQV EGPGISSYTS NAAQAGESLQ GCLEEALVLI PEAQHRKTPT 130 140 150 160 170 180 FLGATAGMRL LSRKNSSQAR DIFAAVTQVL GRSPVDFWGA ELLAGQAEGA FGWITVNYGL 190 200 210 220 230 240 GTLVKYSFTG EWIQPPEEML VGALDMGGAS TQITFVPGGP ILDKSTQADF RLYGSDYSVY 250 260 270 280 290 300 THSYLCFGRD QMLSRLLVGL VQSRPAALLR HPCYLSGYQT TLALGPLYES PCVHATPPLS 310 320 330 340 350 360 LPQNLTVEGT GNPGACVSAI RELFNFSSCQ GQEDCAFDGV YQPPLRGQFY VEASYPGQDR 370 380 390 400 410 420 WLRDYCASGL YILTLLHEGY GFSEETWPSL EFRKQAGGVD IGWTLGYMLN LTGMIPADAP 430 440 450 AQWRAESYGV WVAKVVFMVL ALVAVVGAAL VQLFWLQD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 16752921] [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: 17095758] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, VARIANT PRO-62. Tissue: Liver.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] 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: 15164053] [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: 15489334] [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: 17603550] [Abstract] Cited for: ENZYME REGULATION.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00394874. IPI00550288.
RefSeq	NP_001028285.1. NM_001033113.1. NP_940987.2. NM_198585.2.
UniGene	Hs.512562.
3D structure databases
ProteinModelPortal	Q5MY95.
SMR	Q5MY95. Positions 39-465.
ModBase	Search...
Protein-protein interaction databases
STRING	Q5MY95.
Polymorphism databases
DMDM	158705943.
Proteomic databases
PRIDE	Q5MY95.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371506; ENSP00000360561; ENSG00000188833. ENST00000472938; ENSP00000420531; ENSG00000188833.
GeneID	377841.
KEGG	hsa:377841.
UCSC	uc004cmw.1. human. uc004cmx.1. human.
Organism-specific databases
CTD	377841.
GeneCards	GC09M140328.
HGNC	HGNC:24860. ENTPD8.
HPA	HPA021509.
neXtProt	NX_Q5MY95.
PharmGKB	PA142671906.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16923.
GeneTree	ENSGT00550000074435.
HOGENOM	HBG402995.
HOVERGEN	HBG018982.
InParanoid	Q5MY95.
OMA	SYLCFGR.
PhylomeDB	Q5MY95.
Gene expression databases
ArrayExpress	Q5MY95.
Bgee	Q5MY95.
CleanEx	HS_ENTPD8.
Genevestigator	Q5MY95.
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	100687.

Entry information

Entry name

ENTP8_HUMAN

Accession

Primary (citable) accession number: Q5MY95
Secondary accession number(s): A2BG17, Q6UVZ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 2, 2007
Last sequence update:	October 2, 2007
Last modified:	January 25, 2012
This is version 59 of the entry and version 2 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.