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Protein

Ectonucleoside triphosphate diphosphohydrolase 6

Gene

ENTPD6

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

Functioni

Might support glycosylation reactions in the Golgi apparatus and, when released from cells, might catalyze the hydrolysis of extracellular nucleotides. Hydrolyzes preferentially nucleoside 5'-diphosphates, nucleoside 5'-triphosphates are hydrolyzed only to a minor extent, there is no hydrolysis of nucleoside 5'-monophosphates. The order of activity with different substrates is GDP > IDP >> UDP = CDP >> ADP (By similarity).By similarity

Catalytic activityi

A nucleoside diphosphate + H2O = a nucleoside phosphate + phosphate.

Cofactori

Ca2+By similarity, Mg2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei224 – 2241Proton acceptorBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Calcium, Magnesium

Enzyme and pathway databases

BRENDAi3.6.1.6. 2681.

Names & Taxonomyi

Protein namesi
Recommended name:
Ectonucleoside triphosphate diphosphohydrolase 6 (EC:3.6.1.6)
Short name:
NTPDase 6
Alternative name(s):
CD39 antigen-like 2
Gene namesi
Name:ENTPD6
Synonyms:CD39L2, IL6ST2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:3368. ENTPD6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3939CytoplasmicSequence analysisAdd
BLAST
Transmembranei40 – 6021Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini61 – 484424LumenalSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi215 – 2151C → S: No change in activity. 1 Publication

Organism-specific databases

PharmGKBiPA27803.

Polymorphism and mutation databases

BioMutaiENTPD6.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 484484Ectonucleoside triphosphate diphosphohydrolase 6PRO_0000209913Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi220 – 2201N-linked (GlcNAc...)1 Publication
Glycosylationi284 – 2841N-linked (GlcNAc...)1 Publication
Disulfide bondi325 ↔ 3561 Publication
Disulfide bondi416 ↔ 4301 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO75354.
MaxQBiO75354.
PaxDbiO75354.
PeptideAtlasiO75354.
PRIDEiO75354.

PTM databases

iPTMnetiO75354.
PhosphoSiteiO75354.

Expressioni

Tissue specificityi

Expressed in most tissues, but predominantly in heart.1 Publication

Gene expression databases

BgeeiO75354.
CleanExiHS_ENTPD6.
ExpressionAtlasiO75354. baseline and differential.
GenevisibleiO75354. HS.

Organism-specific databases

HPAiCAB025355.

Interactioni

Protein-protein interaction databases

BioGridi107393. 12 interactions.
IntActiO75354. 4 interactions.
MINTiMINT-3039657.
STRINGi9606.ENSP00000365840.

Structurei

3D structure databases

ProteinModelPortaliO75354.
SMRiO75354. Positions 100-331.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the GDA1/CD39 NTPase family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1385. Eukaryota.
COG5371. LUCA.
GeneTreeiENSGT00510000046675.
HOGENOMiHOG000220904.
HOVERGENiHBG018208.
InParanoidiO75354.
KOiK01511.
OMAiEPLYESC.
OrthoDBiEOG7QVM2K.
PhylomeDBiO75354.
TreeFamiTF315029.

Family and domain databases

InterProiIPR000407. GDA1_CD39_NTPase.
[Graphical view]
PANTHERiPTHR11782. PTHR11782. 2 hits.
PfamiPF01150. GDA1_CD39. 1 hit.
[Graphical view]
PROSITEiPS01238. GDA1_CD39_NTPASE. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O75354-1) [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
MKKGIRYETS RKTSYIFQQP QHGPWQTRMR KISNHGSLRV AKVAYPLGLC
60 70 80 90 100
VGVFIYVAYI KWHRATATQA FFSITRAAPG ARWGQQAHSP LGTAADGHEV
110 120 130 140 150
FYGIMFDAGS TGTRVHVFQF TRPPRETPTL THETFKALKP GLSAYADDVE
160 170 180 190 200
KSAQGIRELL DVAKQDIPFD FWKATPLVLK ATAGLRLLPG EKAQKLLQKV
210 220 230 240 250
KKVFKASPFL VGDDCVSIMN GTDEGVSAWI TINFLTGSLK TPGGSSVGML
260 270 280 290 300
DLGGGSTQIA FLPRVEGTLQ ASPPGYLTAL RMFNRTYKLY SYSYLGLGLM
310 320 330 340 350
SARLAILGGV EGQPAKDGKE LVSPCLSPSF KGEWEHAEVT YRVSGQKAAA
360 370 380 390 400
SLHELCAARV SEVLQNRVHR TEEVKHVDFY AFSYYYDLAA GVGLIDAEKG
410 420 430 440 450
GSLVVGDFEI AAKYVCRTLE TQPQSSPFSC MDLTYVSLLL QEFGFPRSKV
460 470 480
LKLTRKIDNV ETSWALGAIF HYIDSLNRQK SPAS
Length:484
Mass (Da):53,246
Last modified:January 11, 2011 - v3
Checksum:i3CBA96040BC196CB
GO
Isoform 2 (identifier: O75354-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: MKKGIRYETSRKTSYIFQ → M

Show »
Length:467
Mass (Da):51,159
Checksum:i6F6A134332D87D20
GO
Isoform 3 (identifier: O75354-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     19-19: Missing.

Note: No experimental confirmation available.
Show »
Length:483
Mass (Da):53,118
Checksum:iF416E68E031BC8CD
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti14 – 141S → N.1 Publication
Corresponds to variant rs2076559 [ dbSNP | Ensembl ].
VAR_027812
Natural varianti138 – 1381L → V.1 Publication
Corresponds to variant rs1044567 [ dbSNP | Ensembl ].
VAR_017863
Natural varianti157 – 1571R → Q.
Corresponds to variant rs34007133 [ dbSNP | Ensembl ].
VAR_050309
Natural varianti202 – 2021K → E.5 Publications
Corresponds to variant rs6050446 [ dbSNP | Ensembl ].
VAR_027813
Natural varianti323 – 3231S → N.
Corresponds to variant rs6138541 [ dbSNP | Ensembl ].
VAR_027814

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1818MKKGI…SYIFQ → M in isoform 2. 1 PublicationVSP_039122Add
BLAST
Alternative sequencei19 – 191Missing in isoform 3. 1 PublicationVSP_054314

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF039916 mRNA. Translation: AAC39883.1.
AY327581 mRNA. Translation: AAP92131.1.
AL834158 mRNA. Translation: CAD38864.2.
AL035252 Genomic DNA. Translation: CAB41571.1.
AL035252 Genomic DNA. Translation: CAI22592.1.
CH471133 Genomic DNA. Translation: EAX10095.1.
CH471133 Genomic DNA. Translation: EAX10097.1.
CH471133 Genomic DNA. Translation: EAX10098.1.
BC025980 mRNA. Translation: AAH25980.1.
CCDSiCCDS13170.1. [O75354-1]
CCDS46586.1. [O75354-2]
RefSeqiNP_001107561.1. NM_001114089.3.
NP_001238.2. NM_001247.4.
NP_001304870.1. NM_001317941.2.
NP_001309307.1. NM_001322378.1.
NP_001309308.1. NM_001322379.1.
NP_001309309.1. NM_001322380.1.
NP_001309310.1. NM_001322381.1.
NP_001309311.1. NM_001322382.1.
NP_001309312.1. NM_001322383.1.
NP_001309313.1. NM_001322384.1.
NP_001309314.1. NM_001322385.1.
NP_001309315.1. NM_001322386.1.
NP_001309316.1. NM_001322387.1.
NP_001309317.1. NM_001322388.1.
NP_001309318.1. NM_001322389.1.
NP_001309319.1. NM_001322390.1.
NP_001309320.1. NM_001322391.1.
NP_001309321.1. NM_001322392.1.
NP_001309322.1. NM_001322393.1.
NP_001309323.1. NM_001322394.1.
NP_001309324.1. NM_001322395.1.
NP_001309325.1. NM_001322396.1.
NP_001309326.1. NM_001322397.1.
NP_001309327.1. NM_001322398.1.
XP_006723728.1. XM_006723665.2. [O75354-3]
XP_011527698.1. XM_011529396.1. [O75354-1]
XP_011527699.1. XM_011529397.1. [O75354-3]
UniGeneiHs.500375.
Hs.667826.

Genome annotation databases

EnsembliENST00000354989; ENSP00000347084; ENSG00000197586. [O75354-2]
ENST00000360031; ENSP00000353131; ENSG00000197586. [O75354-3]
ENST00000376652; ENSP00000365840; ENSG00000197586. [O75354-1]
GeneIDi955.
KEGGihsa:955.
UCSCiuc002wuj.3. human. [O75354-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF039916 mRNA. Translation: AAC39883.1.
AY327581 mRNA. Translation: AAP92131.1.
AL834158 mRNA. Translation: CAD38864.2.
AL035252 Genomic DNA. Translation: CAB41571.1.
AL035252 Genomic DNA. Translation: CAI22592.1.
CH471133 Genomic DNA. Translation: EAX10095.1.
CH471133 Genomic DNA. Translation: EAX10097.1.
CH471133 Genomic DNA. Translation: EAX10098.1.
BC025980 mRNA. Translation: AAH25980.1.
CCDSiCCDS13170.1. [O75354-1]
CCDS46586.1. [O75354-2]
RefSeqiNP_001107561.1. NM_001114089.3.
NP_001238.2. NM_001247.4.
NP_001304870.1. NM_001317941.2.
NP_001309307.1. NM_001322378.1.
NP_001309308.1. NM_001322379.1.
NP_001309309.1. NM_001322380.1.
NP_001309310.1. NM_001322381.1.
NP_001309311.1. NM_001322382.1.
NP_001309312.1. NM_001322383.1.
NP_001309313.1. NM_001322384.1.
NP_001309314.1. NM_001322385.1.
NP_001309315.1. NM_001322386.1.
NP_001309316.1. NM_001322387.1.
NP_001309317.1. NM_001322388.1.
NP_001309318.1. NM_001322389.1.
NP_001309319.1. NM_001322390.1.
NP_001309320.1. NM_001322391.1.
NP_001309321.1. NM_001322392.1.
NP_001309322.1. NM_001322393.1.
NP_001309323.1. NM_001322394.1.
NP_001309324.1. NM_001322395.1.
NP_001309325.1. NM_001322396.1.
NP_001309326.1. NM_001322397.1.
NP_001309327.1. NM_001322398.1.
XP_006723728.1. XM_006723665.2. [O75354-3]
XP_011527698.1. XM_011529396.1. [O75354-1]
XP_011527699.1. XM_011529397.1. [O75354-3]
UniGeneiHs.500375.
Hs.667826.

3D structure databases

ProteinModelPortaliO75354.
SMRiO75354. Positions 100-331.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107393. 12 interactions.
IntActiO75354. 4 interactions.
MINTiMINT-3039657.
STRINGi9606.ENSP00000365840.

PTM databases

iPTMnetiO75354.
PhosphoSiteiO75354.

Polymorphism and mutation databases

BioMutaiENTPD6.

Proteomic databases

EPDiO75354.
MaxQBiO75354.
PaxDbiO75354.
PeptideAtlasiO75354.
PRIDEiO75354.

Protocols and materials databases

DNASUi955.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000354989; ENSP00000347084; ENSG00000197586. [O75354-2]
ENST00000360031; ENSP00000353131; ENSG00000197586. [O75354-3]
ENST00000376652; ENSP00000365840; ENSG00000197586. [O75354-1]
GeneIDi955.
KEGGihsa:955.
UCSCiuc002wuj.3. human. [O75354-1]

Organism-specific databases

CTDi955.
GeneCardsiENTPD6.
HGNCiHGNC:3368. ENTPD6.
HPAiCAB025355.
MIMi603160. gene.
neXtProtiNX_O75354.
PharmGKBiPA27803.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1385. Eukaryota.
COG5371. LUCA.
GeneTreeiENSGT00510000046675.
HOGENOMiHOG000220904.
HOVERGENiHBG018208.
InParanoidiO75354.
KOiK01511.
OMAiEPLYESC.
OrthoDBiEOG7QVM2K.
PhylomeDBiO75354.
TreeFamiTF315029.

Enzyme and pathway databases

BRENDAi3.6.1.6. 2681.

Miscellaneous databases

ChiTaRSiENTPD6. human.
GeneWikiiENTPD6.
GenomeRNAii955.
PROiO75354.
SOURCEiSearch...

Gene expression databases

BgeeiO75354.
CleanExiHS_ENTPD6.
ExpressionAtlasiO75354. baseline and differential.
GenevisibleiO75354. HS.

Family and domain databases

InterProiIPR000407. GDA1_CD39_NTPase.
[Graphical view]
PANTHERiPTHR11782. PTHR11782. 2 hits.
PfamiPF01150. GDA1_CD39. 1 hit.
[Graphical view]
PROSITEiPS01238. GDA1_CD39_NTPASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The CD39-like gene family: identification of three new human members (CD39L2, CD39L3, and CD39L4), their murine homologues, and a member of the gene family from Drosophila melanogaster."
    Chadwick B.P., Frischauf A.-M.
    Genomics 50:357-367(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS VAL-138 AND GLU-202.
    Tissue: Keratinocyte.
  2. "Bacterial expression, characterization, and disulfide bond determination of soluble human NTPDase6 (CD39L2) nucleotidase: implications for structure and function."
    Ivanenkov V.V., Murphy-Piedmonte D.M., Kirley T.L.
    Biochemistry 42:11726-11735(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-220 AND ASN-284, DISULFIDE BONDS, MUTAGENESIS OF CYS-215, VARIANTS ASN-14 AND GLU-202.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLU-202.
    Tissue: Amygdala.
  4. "The DNA sequence and comparative analysis of human chromosome 20."
    Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
    , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
    Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-202.
  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] (ISOFORM 3), VARIANT GLU-202.
    Tissue: Placenta.
  7. "CD39L2, a gene encoding a human nucleoside diphosphatase, predominantly expressed in the heart."
    Yeung G., Mulero J.J., McGowan D.W., Bajwa S.S., Ford J.E.
    Biochemistry 39:12916-12923(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiENTP6_HUMAN
AccessioniPrimary (citable) accession number: O75354
Secondary accession number(s): A6NCX6
, D3DW49, Q5QPJ2, Q5QPJ5, Q7Z5B5, Q8N3H3, Q8TAS7, Q9UJD1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2001
Last sequence update: January 11, 2011
Last modified: July 6, 2016
This is version 151 of the entry and version 3 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 20
    Human chromosome 20: 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.