Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Ectonucleoside triphosphate diphosphohydrolase 5

Gene

Entpd5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. The nucleotide hydrolyzing preference is GDP > IDP > UDP, 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.2 Publications

Catalytic activityi

GDP + H2O = GMP + phosphate.1 Publication
A nucleoside diphosphate + H2O = a nucleoside phosphate + phosphate.1 Publication

Cofactori

Ca2+1 Publication, Mg2+1 Publication

pH dependencei

Optimum pH is 7.1 Publication

Pathwayi: protein glycosylation

This protein is involved in the pathway protein glycosylation, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein glycosylation and in Protein modification.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei171 – 1711Proton acceptorCurated

GO - Molecular functioni

  • guanosine-diphosphatase activity Source: UniProtKB
  • uridine-diphosphatase activity Source: UniProtKB

GO - Biological processi

  • 'de novo' posttranslational protein folding Source: UniProtKB
  • ATP metabolic process Source: UniProtKB
  • cell growth Source: UniProtKB
  • cell proliferation Source: UniProtKB
  • positive regulation of glycolytic process Source: UniProtKB
  • protein N-linked glycosylation Source: UniProtKB
  • regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Calcium, Magnesium

Enzyme and pathway databases

UniPathwayiUPA00378.

Names & Taxonomyi

Protein namesi
Recommended name:
Ectonucleoside triphosphate diphosphohydrolase 5 (EC:3.6.1.6)
Short name:
NTPDase 5
Alternative name(s):
CD39 antigen-like 4
ER-UDPase
Guanosine-diphosphatase ENTPD5 (EC:3.6.1.42)
Short name:
GDPase ENTPD5
Nucleoside diphosphatase
Uridine-diphosphatase ENTPD5
Short name:
UDPase ENTPD5
Gene namesi
Name:Entpd5
Synonyms:Cd39l4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1321385. Entpd5.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • extracellular exosome Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Secreted

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi171 – 1711E → A: Abolishes enzyme activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence analysisAdd
BLAST
Chaini25 – 427403Ectonucleoside triphosphate diphosphohydrolase 5PRO_0000019910Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi231 – 2311N-linked (GlcNAc...)Sequence analysis
Disulfide bondi271 ↔ 302By similarity
Disulfide bondi362 ↔ 376By similarity

Post-translational modificationi

N-glycosylated; high-mannose type.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9WUZ9.
MaxQBiQ9WUZ9.
PaxDbiQ9WUZ9.
PRIDEiQ9WUZ9.

PTM databases

iPTMnetiQ9WUZ9.
PhosphoSiteiQ9WUZ9.

Expressioni

Tissue specificityi

Ubiquitous.

Inductioni

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.1 Publication

Gene expression databases

BgeeiQ9WUZ9.
CleanExiMM_ENTPD5.
ExpressionAtlasiQ9WUZ9. baseline and differential.
GenevisibleiQ9WUZ9. MM.

Interactioni

Subunit structurei

Exists both as a monomer and a disulfide-linked homodimer, the dimers are enzymatically inactive.By similarity

Protein-protein interaction databases

MINTiMINT-1863980.
STRINGi10090.ENSMUSP00000071939.

Structurei

3D structure databases

ProteinModelPortaliQ9WUZ9.
SMRiQ9WUZ9. Positions 48-419.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the GDA1/CD39 NTPase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1385. Eukaryota.
COG5371. LUCA.
GeneTreeiENSGT00510000046675.
HOGENOMiHOG000220904.
HOVERGENiHBG018208.
InParanoidiQ9WUZ9.
KOiK01511.
OrthoDBiEOG7QVM2K.

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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9WUZ9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATSWGAVFM LIIACVGSTV FYREQQTWFE GVFLSSMCPI NVSAGTFYGI
60 70 80 90 100
MFDAGSTGTR IHVYTFVQKT AGQLPFLEGE IFDSVKPGLS AFVDQPKQGA
110 120 130 140 150
ETVQELLEVA KDSIPRSHWE RTPVVLKATA GLRLLPEQKA QALLLEVEEI
160 170 180 190 200
FKNSPFLVPD GSVSIMDGSY EGILAWVTVN FLTGQLHGRG QETVGTLDLG
210 220 230 240 250
GASTQITFLP QFEKTLEQTP RGYLTSFEMF NSTFKLYTHS YLGFGLKAAR
260 270 280 290 300
LATLGALEAK GTDGHTFRSA CLPRWLEAEW IFGGVKYQYG GNQEGEMGFE
310 320 330 340 350
PCYAEVLRVV QGKLHQPEEV RGSAFYAFSY YYDRAADTHL IDYEKGGVLK
360 370 380 390 400
VEDFERKARE VCDNLGSFSS GSPFLCMDLT YITALLKDGF GFADGTLLQL
410 420
TKKVNNIETG WALGATFHLL QSLGITS
Length:427
Mass (Da):47,102
Last modified:November 1, 1999 - v1
Checksum:i2F9DA2C342C55577
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti218 – 2181Q → K in BAC27461 (PubMed:16141072).Curated
Sequence conflicti390 – 3901F → L in AAC05181 (PubMed:9457681).Curated
Sequence conflicti394 – 42734DGTLL…LGITS → ERHPLTAHKESEQHRDWLGL GGHLSPAPVSGHHQLRPSST SEACISEPVFSQEGVDSETF SDLSGKAWPETR in AAC05181 (PubMed:9457681).CuratedAdd
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS26045.1.
RefSeqiNP_001021385.1. NM_001026214.2.
NP_001272978.1. NM_001286049.1.
NP_001272987.1. NM_001286058.1.
NP_031673.2. NM_007647.3.
XP_006515511.1. XM_006515448.2.
XP_006515512.1. XM_006515449.2.
XP_006515514.1. XM_006515451.2.
UniGeneiMm.10211.

Genome annotation databases

EnsembliENSMUST00000021662; ENSMUSP00000021662; ENSMUSG00000021236.
ENSMUST00000110272; ENSMUSP00000105901; ENSMUSG00000021236.
ENSMUST00000117286; ENSMUSP00000114011; ENSMUSG00000021236.
ENSMUST00000120942; ENSMUSP00000112516; ENSMUSG00000021236.
ENSMUST00000122194; ENSMUSP00000113106; ENSMUSG00000021236.
GeneIDi12499.
KEGGimmu:12499.
UCSCiuc007ofd.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS26045.1.
RefSeqiNP_001021385.1. NM_001026214.2.
NP_001272978.1. NM_001286049.1.
NP_001272987.1. NM_001286058.1.
NP_031673.2. NM_007647.3.
XP_006515511.1. XM_006515448.2.
XP_006515512.1. XM_006515449.2.
XP_006515514.1. XM_006515451.2.
UniGeneiMm.10211.

3D structure databases

ProteinModelPortaliQ9WUZ9.
SMRiQ9WUZ9. Positions 48-419.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-1863980.
STRINGi10090.ENSMUSP00000071939.

PTM databases

iPTMnetiQ9WUZ9.
PhosphoSiteiQ9WUZ9.

Proteomic databases

EPDiQ9WUZ9.
MaxQBiQ9WUZ9.
PaxDbiQ9WUZ9.
PRIDEiQ9WUZ9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021662; ENSMUSP00000021662; ENSMUSG00000021236.
ENSMUST00000110272; ENSMUSP00000105901; ENSMUSG00000021236.
ENSMUST00000117286; ENSMUSP00000114011; ENSMUSG00000021236.
ENSMUST00000120942; ENSMUSP00000112516; ENSMUSG00000021236.
ENSMUST00000122194; ENSMUSP00000113106; ENSMUSG00000021236.
GeneIDi12499.
KEGGimmu:12499.
UCSCiuc007ofd.2. mouse.

Organism-specific databases

CTDi957.
MGIiMGI:1321385. Entpd5.

Phylogenomic databases

eggNOGiKOG1385. Eukaryota.
COG5371. LUCA.
GeneTreeiENSGT00510000046675.
HOGENOMiHOG000220904.
HOVERGENiHBG018208.
InParanoidiQ9WUZ9.
KOiK01511.
OrthoDBiEOG7QVM2K.

Enzyme and pathway databases

UniPathwayiUPA00378.

Miscellaneous databases

ChiTaRSiEntpd5. mouse.
NextBioi281440.
PROiQ9WUZ9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9WUZ9.
CleanExiMM_ENTPD5.
ExpressionAtlasiQ9WUZ9. baseline and differential.
GenevisibleiQ9WUZ9. MM.

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. "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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brown adipose tissue, Kidney, Liver, Lung and Testis.
  9. "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] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, GLYCOSYLATION, SUBCELLULAR LOCATION, INDUCTION, MUTAGENESIS OF GLU-171.

Entry informationi

Entry nameiENTP5_MOUSE
AccessioniPrimary (citable) accession number: Q9WUZ9
Secondary accession number(s): O70214
, Q544J4, Q8BR23, Q8CD29
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2001
Last sequence update: November 1, 1999
Last modified: March 16, 2016
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.