Q9WUZ9 (ENTP5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ectonucleoside triphosphate diphosphohydrolase 5
Short name=NTPDase 5
EC=3.6.1.6

Alternative name(s):
CD39 antigen-like 4
ER-UDPase
Guanosine-diphosphatase ENTPD5
Short name=GDPase ENTPD5
EC=3.6.1.42
Nucleoside diphosphatase
Uridine-diphosphatase ENTPD5
Short name=UDPase ENTPD5

Gene names

Name:	Entpd5
Synonyms:	Cd39l4

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	427 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Uridine diphosphatase (UDPase) that promotes protein N-glycosylation and ATP level regulation. UDP hydrolysis promotes protein N-glycosylation and folding in the endoplasmic reticulum, as well as elevated ATP consumption in the cytosol via an ATP hydrolysis cycle. Together with CMPK1 and AK1, constitutes an ATP hydrolysis cycle that converts ATP to AMP and results in a compensatory increase in aerobic glycolysis. Also hydrolyzes GDP and IDP but not any other nucleoside di-, mono- or triphosphates, nor thiamine pyrophosphate. Plays a key role in the AKT1-PTEN signaling pathway by promoting glycolysis in proliferating cells in response to phosphoinositide 3-kinase (PI3K) signaling. Ref.2 Ref.8
Catalytic activity	GDP + H2O = GMP + phosphate. Ref.8 A nucleoside diphosphate + H2O = a nucleotide + phosphate. Ref.8
Cofactor	Calcium. Ref.2 Magnesium. Ref.2
Pathway	Protein modification; protein glycosylation.
Subcellular location	Endoplasmic reticulum lumen Ref.2 Ref.8.
Tissue specificity	Ubiquitous.
Induction	Expressed in response to phosphoinositide 3-kinase (PI3K) signaling. Activation of PI3K results in FOXO phosphorylation by AKT1 and loss of ENTPD5 transcriptional repression. Up-regulated in PTEN-deficient cells. Ref.8
Post-translational modification	N-glycosylated; high-mannose type. Ref.2 Ref.8
Disruption phenotype	Mice display hepatopathy and aspermia. The hepatopathy is progressive and characterized by centrilobular hepatocyte hypertrophy, oval cell proliferation, bile staining of Kupffer cells, and hepatocyte degeneration with increasing incidence and severity of degenerative lesions, development of multiple foci of cellular alteration, and hepatocellular neoplasia with age. Ref.7
Sequence similarities	Belongs to the GDA1/CD39 NTPase family.
Biophysicochemical properties	pH dependence: Optimum pH is 7. Ref.2

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Domain	Signal
Ligand	Calcium Magnesium
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	'de novo' posttranslational protein folding Inferred from mutant phenotype Ref.8. Source: UniProtKB ATP metabolic process Inferred from mutant phenotype Ref.8. Source: UniProtKB cell growth Inferred from mutant phenotype Ref.8. Source: UniProtKB cell proliferation Inferred from mutant phenotype Ref.8. Source: UniProtKB glycolysis Inferred from mutant phenotype Ref.8. Source: UniProtKB protein N-linked glycosylation Inferred from mutant phenotype Ref.8. Source: UniProtKB regulation of phosphatidylinositol 3-kinase cascade Inferred from mutant phenotype Ref.8. Source: UniProtKB
Cellular component	endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	guanosine-diphosphatase activity Inferred from direct assay Ref.8. Source: UniProtKB uridine-diphosphatase activity Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 427	409	Ectonucleoside triphosphate diphosphohydrolase 5		PRO_0000019910
Sites
	Active site	171	1	Proton acceptor Probable
Amino acid modifications
	Glycosylation	41	1	N-linked (GlcNAc...) Potential
	Glycosylation	231	1	N-linked (GlcNAc...) Potential
Experimental info
	Mutagenesis	171	1	E → A: Abolishes enzyme activity. Ref.8
	Sequence conflict	218	1	Q → K in BAC27461. Ref.4
	Sequence conflict	390	1	F → L in AAC05181. Ref.1
	Sequence conflict	394 – 427	34	DGTLL…LGITS → ERHPLTAHKESEQHRDWLGL GGHLSPAPVSGHHQLRPSST SEACISEPVFSQEGVDSETF SDLSGKAWPETR in AAC05181. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9WUZ9 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 2F9DA2C342C55577	FASTA	427	47,102
	10 20 30 40 50 60 MATSWGAVFM LIIACVGSTV FYREQQTWFE GVFLSSMCPI NVSAGTFYGI MFDAGSTGTR 70 80 90 100 110 120 IHVYTFVQKT AGQLPFLEGE IFDSVKPGLS AFVDQPKQGA ETVQELLEVA KDSIPRSHWE 130 140 150 160 170 180 RTPVVLKATA GLRLLPEQKA QALLLEVEEI FKNSPFLVPD GSVSIMDGSY EGILAWVTVN 190 200 210 220 230 240 FLTGQLHGRG QETVGTLDLG GASTQITFLP QFEKTLEQTP RGYLTSFEMF NSTFKLYTHS 250 260 270 280 290 300 YLGFGLKAAR LATLGALEAK GTDGHTFRSA CLPRWLEAEW IFGGVKYQYG GNQEGEMGFE 310 320 330 340 350 360 PCYAEVLRVV QGKLHQPEEV RGSAFYAFSY YYDRAADTHL IDYEKGGVLK VEDFERKARE 370 380 390 400 410 420 VCDNLGSFSS GSPFLCMDLT YITALLKDGF GFADGTLLQL TKKVNNIETG WALGATFHLL QSLGITS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and chromosomal mapping of a mouse gene with homology to NTPases." Chadwick B.P., Williamson J., Sheer D., Frischauf A.-M. Mamm. Genome 9:162-164(1998) [PubMed: 9457681] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[2]	"Glycoprotein reglucosylation and nucleotide sugar utilization in the secretory pathway: identification of a nucleoside diphosphatase in the endoplasmic reticulum." Trombetta E.S., Helenius A. EMBO J. 18:3282-3292(1999) [PubMed: 10369669] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES. Tissue: Liver.
[3]	"cDNA isolation, expression, and chromosomal localization of the mouse pcph proto-oncogene." Recio J.A., Zambrano N., de La Pena L., Powers C., Siwarski D., Huppi K., Notario V. Mol. Carcinog. 26:130-136(1999) [PubMed: 10506756] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6J. Tissue: Thymus.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Bone, Corpora quadrigemina, Head, Kidney, Testis, Thymus and Urinary bladder.
[5]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Strain: FVB/N. Tissue: Kidney.
[7]	"Ectonucleoside triphosphate diphosphohydrolase type 5 (Entpd5)-deficient mice develop progressive hepatopathy, hepatocellular tumors, and spermatogenic arrest." Read R., Hansen G., Kramer J., Finch R., Li L., Vogel P. Vet. Pathol. 46:491-504(2009) [PubMed: 19176496] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[8]	"The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway." Fang M., Shen Z., Huang S., Zhao L., Chen S., Mak T.W., Wang X. Cell 143:711-724(2010) [PubMed: 21074248] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, GLYCOSYLATION, SUBCELLULAR LOCATION, INDUCTION, MUTAGENESIS OF GLU-171.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF006482 mRNA. Translation: AAC05181.1. AJ238636 mRNA. Translation: CAB45533.1. AF136571 mRNA. Translation: AAK82949.1. AK002618 mRNA. Translation: BAB22234.1. AK031581 mRNA. Translation: BAC27461.1. AK036641 mRNA. Translation: BAC29515.1. AK037736 mRNA. Translation: BAC29861.1. AK045828 mRNA. Translation: BAC32507.1. AK079267 mRNA. Translation: BAC37592.1. AK080265 mRNA. Translation: BAC37862.1. AK081435 mRNA. Translation: BAC38219.1. AK088455 mRNA. Translation: BAC40362.1. AK160950 mRNA. Translation: BAE36110.1. CH466590 Genomic DNA. Translation: EDL02793.1. CH466590 Genomic DNA. Translation: EDL02796.1. CH466590 Genomic DNA. Translation: EDL02797.1. BC015247 mRNA. Translation: AAH15247.1.
IPI	IPI00125514.
RefSeq	NP_001021385.1. NM_001026214.1. NP_031673.2. NM_007647.2.
UniGene	Mm.10211.
3D structure databases
ProteinModelPortal	Q9WUZ9.
SMR	Q9WUZ9. Positions 46-426.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9WUZ9.
Proteomic databases
PRIDE	Q9WUZ9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000021662; ENSMUSP00000021662; ENSMUSG00000021236. ENSMUST00000110272; ENSMUSP00000105901; ENSMUSG00000021236. ENSMUST00000117286; ENSMUSP00000114011; ENSMUSG00000021236. ENSMUST00000120942; ENSMUSP00000112516; ENSMUSG00000021236. ENSMUST00000122194; ENSMUSP00000113106; ENSMUSG00000021236.
GeneID	12499.
KEGG	mmu:12499.
Organism-specific databases
CTD	957.
MGI	MGI:1321385. Entpd5.
Phylogenomic databases
eggNOG	roNOG11142.
GeneTree	ENSGT00510000046675.
HOVERGEN	HBG018208.
InParanoid	Q9WUZ9.
OrthoDB	EOG4JDH6Q.
PhylomeDB	Q9WUZ9.
Gene expression databases
ArrayExpress	Q9WUZ9.
Bgee	Q9WUZ9.
CleanEx	MM_ENTPD5.
Genevestigator	Q9WUZ9.
GermOnline	ENSMUSG00000021236. Mus musculus.
Family and domain databases
InterPro	IPR000407. GDA1_CD39_NTPase. [Graphical view]
KO	K01511.
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	281440.
SOURCE	Search...

Entry information

Entry name

ENTP5_MOUSE

Accession

Primary (citable) accession number: Q9WUZ9
Secondary accession number(s): O70214 , Q544J4, Q8BR23, Q8CD29

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 29, 2001
Last sequence update:	November 1, 1999
Last modified:	November 16, 2011
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program