UniProtKB - O75354 (ENTP6_HUMAN)
Protein
Ectonucleoside triphosphate diphosphohydrolase 6
Gene
ENTPD6
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the hydrolysis of nucleoside triphosphates and diphosphates in a calcium- or magnesium-dependent manner. Has a strong preference for nucleoside diphosphates, preferentially hydrolyzes GDP, IDP, and UDP, with slower hydrolysis of CDP, ITP, GTP, CTP, ADP, and UTP and virtually no hydrolysis of ATP (PubMed:10948193, PubMed:14529283, PubMed:11041856). The membrane bound form might support glycosylation reactions in the Golgi apparatus and, when released from cells, might catalyze the hydrolysis of extracellular nucleotides (PubMed:10948193, PubMed:14529283, PubMed:11041856).3 Publications
Catalytic activityi
- a ribonucleoside 5'-diphosphate + H2O = a ribonucleoside 5'-phosphate + H+ + phosphate3 PublicationsEC:3.6.1.63 Publications
- EC:3.6.1.62 Publications
- EC:3.6.1.62 Publications
- EC:3.6.1.62 Publications
Cofactori
Ca2+3 Publications, Mg2+3 PublicationsNote: Strongly and equally activated by either Ca2+ or Mg2+.1 Publication
Activity regulationi
Glycosylation does not appear to be required for enzymatic activity.1 Publication
Kineticsi
- KM=130 µM for GDP (in the presence of Ca2+)1 Publication
- Vmax=60000 µmol/h/mg enzyme with GDP as substrate1 Publication
pH dependencei
Optimum pH is 7.0 to 7.4.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 224 | Proton acceptorBy similarity | 1 |
GO - Molecular functioni
- cytidine-diphosphatase activity Source: UniProtKB
- guanosine-5'-triphosphate,3'-diphosphate diphosphatase activity Source: Ensembl
- guanosine-diphosphatase activity Source: UniProtKB
- inosine-diphosphatase activity Source: UniProtKB
- nucleoside-diphosphatase activity Source: UniProtKB
- nucleoside-triphosphatase activity Source: Ensembl
- uridine-diphosphatase activity Source: UniProtKB
GO - Biological processi
- nucleobase-containing small molecule catabolic process Source: Reactome
- nucleoside diphosphate catabolic process Source: GO_Central
- response to calcium ion Source: Ensembl
- response to magnesium ion Source: Ensembl
Keywordsi
Molecular function | Hydrolase |
Ligand | Calcium, Magnesium |
Enzyme and pathway databases
BRENDAi | 3.6.1.6, 2681 |
PathwayCommonsi | O75354 |
Reactomei | R-HSA-8850843, Phosphate bond hydrolysis by NTPDase proteins |
Names & Taxonomyi
Protein namesi | Recommended name: Ectonucleoside triphosphate diphosphohydrolase 6 (EC:3.6.1.63 Publications)Short name: NTPDase 6 Alternative name(s): CD39 antigen-like 2 |
Gene namesi | Name:ENTPD6 Synonyms:CD39L2, IL6ST2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3368, ENTPD6 |
MIMi | 603160, gene |
neXtProti | NX_O75354 |
VEuPathDBi | HostDB:ENSG00000197586.12 |
Subcellular locationi
Extracellular region or secreted
- Secreted 2 Publications
Plasma membrane
- Cell membrane 2 Publications; Single-pass type II membrane protein Sequence analysis
Golgi apparatus
- Golgi apparatus membrane By similarity; Single-pass type II membrane protein Sequence analysis
Note: Exists as a secreted and membrane-bound forms in the medium of transfected cells, the secreted form is predominant.2 Publications
Extracellular region or secreted
- extracellular region Source: UniProtKB
- extracellular space Source: Ensembl
Golgi apparatus
- Golgi apparatus Source: HPA
- Golgi membrane Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- cell surface Source: Ensembl
- integral component of membrane Source: UniProtKB-KW
- membrane Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 39 | CytoplasmicSequence analysisAdd BLAST | 39 | |
Transmembranei | 40 – 60 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 61 – 484 | LumenalSequence analysisAdd BLAST | 424 |
Keywords - Cellular componenti
Cell membrane, Golgi apparatus, Membrane, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 215 | C → S: Does not affect nucleoside-triphosphatase activity. Does not affeet KM for GDP. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 955 |
OpenTargetsi | ENSG00000197586 |
PharmGKBi | PA27803 |
Miscellaneous databases
Pharosi | O75354, Tbio |
Genetic variation databases
BioMutai | ENTPD6 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000209913 | 1 – 484 | Ectonucleoside triphosphate diphosphohydrolase 6Add BLAST | 484 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 220 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 284 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 325 ↔ 356 | 1 Publication | ||
Disulfide bondi | 416 ↔ 430 | 1 Publication |
Post-translational modificationi
The secreted form may be produced by intracellular processing.1 Publication
N-glycosylated.2 Publications
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | O75354 |
MassIVEi | O75354 |
MaxQBi | O75354 |
PaxDbi | O75354 |
PeptideAtlasi | O75354 |
PRIDEi | O75354 |
ProteomicsDBi | 49920 [O75354-1] 49921 [O75354-2] 63663 |
PTM databases
GlyGeni | O75354, 3 sites, 1 O-linked glycan (1 site) |
iPTMneti | O75354 |
PhosphoSitePlusi | O75354 |
Expressioni
Tissue specificityi
Expressed in most tissues, but predominantly in heart.1 Publication
Gene expression databases
Bgeei | ENSG00000197586, Expressed in adenohypophysis and 220 other tissues |
ExpressionAtlasi | O75354, baseline and differential |
Genevisiblei | O75354, HS |
Organism-specific databases
HPAi | ENSG00000197586, Low tissue specificity |
Interactioni
Subunit structurei
Monomer.
1 PublicationProtein-protein interaction databases
BioGRIDi | 107393, 18 interactors |
IntActi | O75354, 9 interactors |
MINTi | O75354 |
STRINGi | 9606.ENSP00000365840 |
Miscellaneous databases
RNActi | O75354, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the GDA1/CD39 NTPase family.Curated
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1385, Eukaryota |
GeneTreei | ENSGT01000000214587 |
InParanoidi | O75354 |
OMAi | CLPPGFK |
OrthoDBi | 1337265at2759 |
PhylomeDBi | O75354 |
TreeFami | TF315029 |
Family and domain databases
InterProi | View protein in InterPro IPR000407, GDA1_CD39_NTPase |
PANTHERi | PTHR11782, PTHR11782, 1 hit |
Pfami | View protein in Pfam PF01150, GDA1_CD39, 1 hit |
PROSITEi | View protein in PROSITE PS01238, GDA1_CD39_NTPASE, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 10 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: O75354-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ5QPI9 | Q5QPI9_HUMAN | Ectonucleoside triphosphate diphosp... | ENTPD6 | 437 | Annotation score: | ||
Q5QPJ6 | Q5QPJ6_HUMAN | Ectonucleoside triphosphate diphosp... | ENTPD6 | 296 | Annotation score: | ||
Q5QPJ3 | Q5QPJ3_HUMAN | Ectonucleoside triphosphate diphosp... | ENTPD6 | 300 | Annotation score: | ||
Q5QPI7 | Q5QPI7_HUMAN | Ectonucleoside triphosphate diphosp... | ENTPD6 | 226 | Annotation score: | ||
Q5QPJ7 | Q5QPJ7_HUMAN | Ectonucleoside triphosphate diphosp... | ENTPD6 | 194 | Annotation score: | ||
H0Y3D0 | H0Y3D0_HUMAN | Ectonucleoside triphosphate diphosp... | ENTPD6 | 295 | Annotation score: | ||
Q5QPJ4 | Q5QPJ4_HUMAN | Ectonucleoside triphosphate diphosp... | ENTPD6 | 188 | Annotation score: | ||
H0Y473 | H0Y473_HUMAN | Ectonucleoside triphosphate diphosp... | ENTPD6 | 313 | Annotation score: | ||
H0Y5X0 | H0Y5X0_HUMAN | Ectonucleoside triphosphate diphosp... | ENTPD6 | 150 | Annotation score: | ||
H0Y6Q1 | H0Y6Q1_HUMAN | Ectonucleoside triphosphate diphosp... | ENTPD6 | 311 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_027812 | 14 | S → N1 PublicationCorresponds to variant dbSNP:rs2076559Ensembl. | 1 | |
Natural variantiVAR_017863 | 138 | L → V1 PublicationCorresponds to variant dbSNP:rs1044567Ensembl. | 1 | |
Natural variantiVAR_050309 | 157 | R → Q. Corresponds to variant dbSNP:rs34007133Ensembl. | 1 | |
Natural variantiVAR_027813 | 202 | K → E5 PublicationsCorresponds to variant dbSNP:rs6050446Ensembl. | 1 | |
Natural variantiVAR_027814 | 323 | S → N. Corresponds to variant dbSNP:rs6138541Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_039122 | 1 – 18 | MKKGI…SYIFQ → M in isoform 2. 1 PublicationAdd BLAST | 18 | |
Alternative sequenceiVSP_054314 | 19 | Missing in isoform 3. 1 Publication | 1 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000354989; ENSP00000347084; ENSG00000197586 [O75354-2] ENST00000360031; ENSP00000353131; ENSG00000197586 [O75354-3] ENST00000376652; ENSP00000365840; ENSG00000197586 [O75354-1] |
GeneIDi | 955 |
KEGGi | hsa:955 |
UCSCi | uc002wuj.3, human [O75354-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
SMRi | O75354 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 107393, 18 interactors |
IntActi | O75354, 9 interactors |
MINTi | O75354 |
STRINGi | 9606.ENSP00000365840 |
PTM databases
GlyGeni | O75354, 3 sites, 1 O-linked glycan (1 site) |
iPTMneti | O75354 |
PhosphoSitePlusi | O75354 |
Genetic variation databases
BioMutai | ENTPD6 |
Proteomic databases
jPOSTi | O75354 |
MassIVEi | O75354 |
MaxQBi | O75354 |
PaxDbi | O75354 |
PeptideAtlasi | O75354 |
PRIDEi | O75354 |
ProteomicsDBi | 49920 [O75354-1] 49921 [O75354-2] 63663 |
Protocols and materials databases
Antibodypediai | 24986, 97 antibodies |
DNASUi | 955 |
Genome annotation databases
Ensembli | ENST00000354989; ENSP00000347084; ENSG00000197586 [O75354-2] ENST00000360031; ENSP00000353131; ENSG00000197586 [O75354-3] ENST00000376652; ENSP00000365840; ENSG00000197586 [O75354-1] |
GeneIDi | 955 |
KEGGi | hsa:955 |
UCSCi | uc002wuj.3, human [O75354-1] |
Organism-specific databases
CTDi | 955 |
DisGeNETi | 955 |
GeneCardsi | ENTPD6 |
HGNCi | HGNC:3368, ENTPD6 |
HPAi | ENSG00000197586, Low tissue specificity |
MIMi | 603160, gene |
neXtProti | NX_O75354 |
OpenTargetsi | ENSG00000197586 |
PharmGKBi | PA27803 |
VEuPathDBi | HostDB:ENSG00000197586.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1385, Eukaryota |
GeneTreei | ENSGT01000000214587 |
InParanoidi | O75354 |
OMAi | CLPPGFK |
OrthoDBi | 1337265at2759 |
PhylomeDBi | O75354 |
TreeFami | TF315029 |
Enzyme and pathway databases
BRENDAi | 3.6.1.6, 2681 |
PathwayCommonsi | O75354 |
Reactomei | R-HSA-8850843, Phosphate bond hydrolysis by NTPDase proteins |
Miscellaneous databases
BioGRID-ORCSi | 955, 1 hit in 993 CRISPR screens |
ChiTaRSi | ENTPD6, human |
GeneWikii | ENTPD6 |
GenomeRNAii | 955 |
Pharosi | O75354, Tbio |
PROi | PR:O75354 |
RNActi | O75354, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000197586, Expressed in adenohypophysis and 220 other tissues |
ExpressionAtlasi | O75354, baseline and differential |
Genevisiblei | O75354, HS |
Family and domain databases
InterProi | View protein in InterPro IPR000407, GDA1_CD39_NTPase |
PANTHERi | PTHR11782, PTHR11782, 1 hit |
Pfami | View protein in Pfam PF01150, GDA1_CD39, 1 hit |
PROSITEi | View protein in PROSITE PS01238, GDA1_CD39_NTPASE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ENTP6_HUMAN | |
Accessioni | O75354Primary (citable) accession number: O75354 Secondary accession number(s): A6NCX6 Q9UJD1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 29, 2001 |
Last sequence update: | January 11, 2011 | |
Last modified: | April 7, 2021 | |
This is version 187 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 20
Human chromosome 20: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families