ENTPD1 encodes CD39/NTPDase1, a cell-surface ectonucleotidase that hydrolyzes extracellular nucleoside triphosphates and diphosphates. Its ATP and ADP hydrolysis produces AMP and inorganic phosphate and requires divalent cations. By removing extracellular platelet-activating ADP, CD39 suppresses platelet aggregation and modulates extracellular nucleotide signaling. Conversion of the resulting AMP to adenosine requires a separate ecto-5-prime-nucleotidase such as CD73. By lowering extracellular ATP and ADP and supplying AMP for CD73-dependent adenosine formation, CD39 contributes to purinergic immune regulation. The full-length protein has a large extracellular catalytic region flanked by membrane-spanning segments; reported alternative products differ at their termini or within this region and are not all functionally characterized.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003924 GTPase activity | EXP PMID:8529670 Purification and properties of human placental ATP diphospho... | ACCEPT | Summary: Purified human placental ATP diphosphohydrolase hydrolyzes GTP. Reason: Table 3 measures phosphate release with GTP; the purified preparation lacks detectable monophosphate and nonspecific alkaline-phosphatase activity. Methods and Fig. 4 establish divalent-cation-dependent catalysis. This supports GTPase activity as substrate chemistry, without assigning a signaling-GTPase mechanism or equal activity to all natural products. See PMID:8529670, pp.67,70–71, Enzymic assays, Fig.2, Fig.4 and Table3; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1995.066_c.x. Supporting Evidence: |
| GO:0003924 GTPase activity | EXP PMID:8626624 CD39 is an ecto-(Ca2+,Mg2+)-apyrase. | ACCEPT | Summary: Independent original human enzyme measurements support GTPase activity. Reason: Only Methods, part of Results and Discussion were recovered for PMID:8626624; its full substrate table remains inaccessible. The biological claim is nevertheless established independently by PMID:8529670, Materials and Methods (Enzymic assays) and Table3 p71: purified human placental enzyme hydrolyzes GTP with phosphate release. The enzyme preparation was not isoform resolved, so no activity is assigned equally to all six natural products. This accepts the supported whole-gene activity without claiming the unread portion of the original citation was verified. Original: https://doi.org/10.1111/j.1432-1033.1995.066_c.x. |
| GO:0003924 GTPase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea maps the measured guanine-triphosphate hydrolysis reaction. Reason: RHEA:19669 is GTP + water to GDP + inorganic phosphate. Human placental Table 3 directly tests GTP; this is nucleotide hydrolysis, without implying a G-protein signaling switch. Evidence: Rhea https://www.rhea-db.org/rhea/19669; human PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:19669 SUPPORTS TRANSFER GTP + H2O = GDP + phosphate + H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. |
| GO:0004050 apyrase activity | EXP PMID:8529670 Purification and properties of human placental ATP diphospho... | ACCEPT | Summary: Purified human placental ATP diphosphohydrolase hydrolyzes ATP and ADP. Reason: Table 3 measures phosphate release with ATP and ADP; the purified preparation lacks detectable monophosphate and nonspecific alkaline-phosphatase activity. Methods and Fig. 4 establish divalent-cation-dependent catalysis. This supports apyrase activity as substrate chemistry, without assigning equal activity to all natural products. See PMID:8529670, pp.67,70–71, Enzymic assays, Fig.2, Fig.4 and Table3; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1995.066_c.x. Supporting Evidence: |
| GO:0004050 apyrase activity | EXP PMID:8626624 CD39 is an ecto-(Ca2+,Mg2+)-apyrase. | ACCEPT | Summary: Independent original human enzyme measurements support apyrase activity. Reason: Only Methods, part of Results and Discussion were recovered for PMID:8626624; its full substrate table remains inaccessible. The biological claim is nevertheless established independently by PMID:8529670, Materials and Methods (Enzymic assays) and Table3 p71: purified human placental enzyme hydrolyzes ATP and ADP with phosphate release. The enzyme preparation was not isoform resolved, so no activity is assigned equally to all six natural products. This accepts the supported whole-gene activity without claiming the unread portion of the original citation was verified. Original: https://doi.org/10.1111/j.1432-1033.1995.066_c.x. Independent intact human/pig endothelial assays also support ATP/ADP hydrolysis (PMID:8996251 Methods sec8 and Results sec20/Fig2; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/); pig TLC and human-cell observations remain distinct. |
| GO:0004050 apyrase activity | EXP PMID:8955160 Identification and characterization of CD39/vascular ATP dip... | ACCEPT | Summary: Independent original human enzyme measurements support apyrase activity. Reason: PMID:8955160 was verified by PubMed/publisher metadata and abstract; operative full text remains inaccessible. The biological claim is nevertheless established independently by PMID:8529670, Materials and Methods (Enzymic assays) and Table3 p71: purified human placental enzyme hydrolyzes ATP and ADP with phosphate release. The enzyme preparation was not isoform resolved, so no activity is assigned equally to all six natural products. This accepts the supported whole-gene activity without claiming the unread portion of the original citation was verified. Original: https://doi.org/10.1111/j.1432-1033.1995.066_c.x. Independent intact human/pig endothelial assays also support ATP/ADP hydrolysis (PMID:8996251 Methods sec8 and Results sec20/Fig2; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/); pig TLC and human-cell observations remain distinct. |
| GO:0004050 apyrase activity | EXP PMID:8996251 Loss of ATP diphosphohydrolase activity with endothelial cel... | ACCEPT | Summary: Endothelial ATPDase hydrolyzes extracellular ATP and ADP with inorganic phosphate release. Reason: Methods assay intact human and porcine EC with ATP or ADP and quantify inorganic phosphate. Results establish divalent-cation-dependent ATPDase activity; porcine Fig.2 resolves ADP conversion to AMP. Human surface CD39 is demonstrated in Fig.5. Together these support apyrase activity; ATP and ADP instantiate the broader nucleotide classes, without claiming every nucleotide or every isoform was tested. Adenosine appears downstream through a separate 5-prime-nucleotidase step, not ENTPD1 monophosphatase activity. See PMID:8996251, sec8 Methods, sec20 Results/Fig.2 and sec22/Fig.5; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/. Supporting Evidence: |
| GO:0004050 apyrase activity | IEA GO_REF:0000120 | ACCEPT | Summary: ENTPD1 catalyzes successive NTP and NDP hydrolysis to NMP. Reason: The ATP/ADP chemistry is established by the human placental and endothelial originals and RHEA:20988/36795. ARBA00098101 currently returns 404, but that provenance gap does not negate the independently supported apyrase activity. The merged row does not establish every listed nucleotide reaction equally: the UTP-specific route is inferred from rat evidence, and individual CDP/UDP judgments remain separate. Evidence: Rhea https://www.rhea-db.org/rhea/20988 and https://www.rhea-db.org/rhea/36795; PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x); PMID8996251 Methodssec8/Resultssec20 (https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/). Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00098101 SOURCE STALE OR MISSING Current official endpoint returns404; historical rule content was not recovered. Independent routes are evaluated separately. RHEA:20988 SUPPORTS TRANSFER ATP + 2 H2O = AMP + 2 phosphate + 2 H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. RHEA:36795 SUPPORTS TRANSFER a ribonucleoside 5'-triphosphate + 2 H2O = a ribonucleoside 5'-phosphate + 2 phosphate + 2 H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. RHEA:64896 SOURCE WEAK OR INFERRED UTP + 2 H2O = UMP + 2 phosphate + 2 H(+). Human record is inferred from rat P97687; operative rat UTP result not recovered here. RHEA:64904 SUPPORTS TRANSFER GTP + 2 H2O = GMP + 2 phosphate + 2 H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. RHEA:64908 SUPPORTS TRANSFER CTP + 2 H2O = CMP + 2 phosphate + 2 H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. RHEA:77735 SUPPORTS TRANSFER ITP + 2 H2O = IMP + 2 phosphate + 2 H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. EC:3.6.1.5 SUPPORTS TRANSFER UniProt source EC designation corresponds to the supported apyrase chemistry; individual nucleotide specificity is not inferred from EC membership alone. |
| GO:0004382 GDP phosphatase activity | EXP PMID:8529670 Purification and properties of human placental ATP diphospho... | ACCEPT | Summary: Purified human placental ATP diphosphohydrolase hydrolyzes GDP. Reason: Table 3 measures phosphate release with GDP; the purified preparation lacks detectable monophosphate and nonspecific alkaline-phosphatase activity. Methods and Fig. 4 establish divalent-cation-dependent catalysis. This supports GDP phosphatase activity as substrate chemistry, without assigning equal activity to all natural products. See PMID:8529670, pp.67,70–71, Enzymic assays, Fig.2, Fig.4 and Table3; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1995.066_c.x. Supporting Evidence: |
| GO:0004382 GDP phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The ancestral GDP-phosphatase assertion is retained in the ENTPD1 lineage. Reason: Human placental Table 3 independently measures GDP hydrolysis. Target membership and the actual IBD node support inheritance; the target P49961 appearing among the experimental donors is valid grounding, not circularity. PANTHER PTHR11782 target PTN002483056 descends from PTN000207579; the pinned IBD row exactly matches the imported donor set and no NOT record for this term appears on the target path. Current MSA ungapped target sequence matches P49961 exactly. Evidence: PAINT PTHR11782/PTN000207579 (https://www.pantherdb.org/panther/family.do?clsAccession=PTHR11782); PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000207579 SUPPORTS TRANSFER Actual IBD at PTN000207579 and matching donor set recovered; P49961 descends from this node with no term-specific target-path NOT. Self-donor presence is valid experimental grounding where present. |
| GO:0004382 GDP phosphatase activity | IEA GO_REF:0000116 | ACCEPT | Summary: GDP is hydrolyzed to GMP with release of inorganic phosphate. Reason: RHEA:22156 has the correct GDP-phosphatase chemistry, and human placental Table 3 independently measures GDP turnover. Evidence: https://www.rhea-db.org/rhea/22156; PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:22156 SUPPORTS TRANSFER GDP + H2O = GMP + phosphate + H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. |
| GO:0005515 protein binding | IPI PMID:16478441 RanBPM associates with CD39 and modulates ecto-nucleotidase ... | KEEP AS NON CORE | Summary: Supported RanBPM association. Reason: PMID:16478441 Results, Table 1 and Figures 1–2 combine human N-terminal bait, reciprocal transfected-cell co-immunoprecipitation and endogenous human B-cell complexes to support RanBPM association. Figure 3 shows RanBPM decreasing CD39 ATP/ADP hydrolysis; CD39 is the regulated enzyme in that experiment, not an enzyme regulator or adapter. The association is supported as a contextual interaction, but no evidence-backed, more specific molecular-function replacement for CD39 is established. Original: https://doi.org/10.1042/BJ20051568; https://pmc.ncbi.nlm.nih.gov/articles/PMC1449986/ (Experimental, Results, Table 1 and Figures 1–3). Supporting Evidence: |
| GO:0005604 basement membrane | IEA GO_REF:0000107 | REMOVE | Summary: The basement-membrane transfer misinterprets the donor localization evidence. Reason: GO:0005604 describes extracellular matrix, not an endothelial cell membrane adjacent to it. Current mouse P55772 traces to PMID:11929769 IDA. The original mouse-tissue Methods and Results with Figures3–5 captions distinguish NTPDase1 on endothelium and some smooth muscle from NTPDase2 on adventitial cells/pericytes associated with laminin and basal membrane. They do not demonstrate NTPDase1 as a basement-membrane component. Orthology is correct; the source localization interpretation is the problem. This judgment follows the actual original, not the paralog in its title. Evidence: PMID11929769 DOI https://doi.org/10.1182/blood.v99.8.2801; author original linked in ENTPD1-reference-guide.md. Immunohistochemistry/Triple staining Methods; localization Results and Figures3–5 captions. GO definition https://www.ebi.ac.uk/QuickGO/term/GO:0005604; donor https://www.uniprot.org/uniprotkb/P55772/entry. Propagation Review Root cause: SOURCE BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:P55772 SOURCE BAD Mouse Entpd1 orthology is correct. The current donor GO0005604 IDA cites PMID11929769; actual tissue localization distinguishes endothelial NTPDase1 from pericyte/adventitial NTPDase2 and does not establish NTPDase1 in basement-membrane matrix. ensembl:ENSMUSP00000107850 SOURCE BAD Mouse Entpd1 orthology is correct. The current donor GO0005604 IDA cites PMID11929769; actual tissue localization distinguishes endothelial NTPDase1 from pericyte/adventitial NTPDase2 and does not establish NTPDase1 in basement-membrane matrix. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ENTPD1 inherits plasma-membrane localization. Reason: The target lies within the Bilateria IBD clade for this location. Human endothelial surface CD39 and intact-cell ectonucleotidase assays independently support the location; the target self-donor is legitimate experimental grounding. PANTHER PTHR11782 target PTN002483056 descends from PTN000925965; the pinned IBD row exactly matches the imported donor set and no NOT record for this term appears on the target path. Current MSA ungapped target sequence matches P49961 exactly. Evidence: PAINT PTHR11782/PTN000925965 (https://www.pantherdb.org/panther/family.do?clsAccession=PTHR11782); PMID8996251 sec22/Fig5 (https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000925965 SUPPORTS TRANSFER Actual IBD at PTN000925965 and matching donor set recovered; P49961 descends from this node with no term-specific target-path NOT. Self-donor presence is valid experimental grounding where present. |
| GO:0005886 plasma membrane | IDA PMID:10636909 Palmitoylation targets CD39/endothelial ATP diphosphohydrola... | ACCEPT | Summary: CD39 localizes to the plasma membrane. Reason: PMID:10636909 Figures 4–5 localize human CD39 antigen and activity at the cell surface. Original: https://doi.org/10.1074/jbc.275.3.2057 (Experimental Procedures and localization Results/Figures4–5). Supporting Evidence: |
| GO:0005886 plasma membrane | NAS PMID:8955160 Identification and characterization of CD39/vascular ATP dip... | ACCEPT | Summary: Human CD39 is localized to the plasma membrane. Reason: PMID:8955160 is abstract-only in the reviewed access set. Independently, PMID:10636909 Experimental Procedures (Cell Culture, Enzyme Cytochemistry and Immunostaining) and Results (Electron Microscopy and Cytochemistry; Figs4–5) identify native human HUVEC surface CD39 and human CD39 expressed in COS-7 cells. PMID:8996251 sec22/Fig5 also detects surface CD39 in human endothelial cells. These inspected originals establish the plasma-membrane location; they do not identify all natural products or reverify the unread 1996 assay. https://doi.org/10.1074/jbc.275.3.2057; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/. |
| GO:0005886 plasma membrane | TAS PMID:7930580 The CD39 lymphoid cell activation antigen. Molecular cloning... | ACCEPT | Summary: CD39 is a plasma-membrane ectonucleotidase; this location is independently established in native human endothelial cells. Reason: PMID:7930580 describes human CD39 cell-surface topology in its accessible publisher abstract, although its full PDF was not recovered. Independent original evidence in PMID:10636909, Experimental Procedures (Cell Culture, Enzyme Cytochemistry and Immunostaining with Anti-CD39) and Results (Electron Microscopy and Cytochemistry; Figure 5A–B), detects endogenous CD39 antigen and enzyme activity in native human HUVEC plasmalemmal caveolae-like structures. Figure 4B separately examines human CD39 expressed in COS-7 cells. These experiments support plasma-membrane localization without assigning all natural isoforms the same distribution or claiming that the 1994 full text was read. Public originals: https://doi.org/10.4049/jimmunol.153.8.3574; https://doi.org/10.1074/jbc.275.3.2057. See ENTPD1-reference-guide.md for access limits. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8850846 | ACCEPT | Summary: Reactome places the NTP-hydrolyzing ENTPD1 catalyst at the plasma membrane. Reason: Event8850846 uses catalyst8850850 and complex8850845, containing NTPDase1 complex8850847 and human protein913566, whose reference identifier is P49961 (residues1–510). The event converts extracellular NTP to NDP plus inorganic phosphate. This verifies the specific human protein rather than relying on a pathway label. Evidence: Reactome https://reactome.org/content/detail/R-HSA-8850846; catalyst8850850 -> complex8850845 -> complex8850847 -> protein913566/P49961. Supporting Evidence: Reactome:R-HSA-8850846 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8850854 | ACCEPT | Summary: Reactome places the NDP-hydrolyzing ENTPD1 catalyst at the plasma membrane. Reason: Event8850854 uses catalyst8850852 and complex8850845, through8850847 to human protein913566/P49961 (residues1–510). The event converts extracellular NDP to NMP plus inorganic phosphate. Calcium/magnesium is modeled as a set of alternatives, not a requirement for both simultaneously. Evidence: Reactome https://reactome.org/content/detail/R-HSA-8850854; catalyst8850852 -> complex8850845 -> complex8850847 -> protein913566/P49961. Supporting Evidence: Reactome:R-HSA-8850854 |
| GO:0005901 caveola | IDA PMID:10636909 Palmitoylation targets CD39/endothelial ATP diphosphohydrola... | KEEP AS NON CORE | Summary: Caveolar localization is supported. Reason: PMID:10636909 Figures 4–5 support caveolar enrichment in the studied cells, a contextual location within the plasma membrane. Original: https://doi.org/10.1074/jbc.275.3.2057 (Experimental Procedures and localization Results/Figures4–5). Supporting Evidence: |
| GO:0005901 caveola | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Caveolar enrichment is a supported cellular context for CD39. Reason: The official SL-0035 mapping is caveola. The target UniProt location cites PMID:10636909, whose human HUVEC/COS-7 experiments support membrane-domain association. Retain as a contextual specialization consistent with the experimental caveola row, without making every cell type or natural product caveolar. Synthetic N-terminal deletion is not a natural-isoform experiment. Evidence: PMID10636909 https://doi.org/10.1074/jbc.275.3.2057, Experimental Procedures and localization Results/Figs4–5; mapping https://rest.uniprot.org/locations/SL-0035.json. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0035 SUPPORTS TRANSFER Official location-to-GO mapping verified; target experimental location and the scope of the refinement are assessed separately. |
| GO:0007155 cell adhesion | NAS PMID:7930580 The CD39 lymphoid cell activation antigen. Molecular cloning... | UNDECIDED | Summary: The scope of the reported antibody-induced homotypic B-cell adhesion remains unresolved from the accessible source. Reason: The publisher abstract of PMID:7930580 describes an earlier observation that ligation by a subset of anti-CD39 antibodies promotes homotypic B-cell adhesion and then describes cloning and epitope mapping. The operative full text and adhesion experiments were not recovered. GO:0007155 concerns attachment through cell-adhesion molecules; the accessible evidence does not resolve how CD39 contributes to that attachment or whether a regulatory term would better capture the reported experiment. Preserve uncertainty without denying the biological observation, requiring CD39 to be the only adhesion component, or inferring a curator error from incomplete access. Public originals: https://doi.org/10.4049/jimmunol.153.8.3574. See ENTPD1-reference-guide.md for access limits. Supporting Evidence: |
| GO:0007596 blood coagulation | TAS PMID:8955160 Identification and characterization of CD39/vascular ATP dip... | MODIFY | Summary: Extracellular ADP hydrolysis negatively regulates platelet aggregation. Reason: PMID:8955160 is correctly identified but its operative full text was not recovered. Independently read PMID:8996251 Methods and Results sec19/Fig1 establish inhibition of human platelet aggregation by human and porcine endothelial cells; inhibition is lost for nonhydrolyzable ADP-beta-S, connecting the effect to extracellular nucleotide hydrolysis. Negative regulation of platelet aggregation captures this demonstrated enzymatic contribution more precisely than the imported blood coagulation term. This is refinement using independent original evidence, not an assertion that the unread experimental citation is wrong. See https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/, sec19/Fig1. Proposed replacements: negative regulation of platelet aggregation |
| GO:0009134 nucleoside diphosphate catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: ENTPD1 directly catalyzes nucleoside-diphosphate degradation. Reason: The Eukaryota IBD ancestor places this catalytic process on the target lineage. Human ADP/GDP/IDP phosphate-release assays establish that the enzyme performs the chemical step; this is not an inference from a substrate merely being necessary for a process. PANTHER PTHR11782 target PTN002483056 descends from PTN000746626; the pinned IBD row exactly matches the imported donor set and no NOT record for this term appears on the target path. Current MSA ungapped target sequence matches P49961 exactly. Evidence: PAINT PTHR11782/PTN000746626 (https://www.pantherdb.org/panther/family.do?clsAccession=PTHR11782); PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000746626 SUPPORTS TRANSFER Actual IBD at PTN000746626 and matching donor set recovered; P49961 descends from this node with no term-specific target-path NOT. Self-donor presence is valid experimental grounding where present. |
| GO:0009203 ribonucleoside triphosphate catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: ENTPD1 directly catalyzes ribonucleoside-triphosphate degradation. Reason: The Eukaryota IBD ancestor places this process on the target lineage. Human ATP/GTP/ITP/CTP phosphate-release assays directly support catalytic participation in degradation; the enzyme, not a consumed substrate, performs the step. PANTHER PTHR11782 target PTN002483056 descends from PTN000746626; the pinned IBD row exactly matches the imported donor set and no NOT record for this term appears on the target path. Current MSA ungapped target sequence matches P49961 exactly. Evidence: PAINT PTHR11782/PTN000746626 (https://www.pantherdb.org/panther/family.do?clsAccession=PTHR11782); PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000746626 SUPPORTS TRANSFER Actual IBD at PTN000746626 and matching donor set recovered; P49961 descends from this node with no term-specific target-path NOT. Self-donor presence is valid experimental grounding where present. |
| GO:0009897 external side of plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: The extracellular catalytic domain acts at the external plasma-membrane surface. Reason: Mouse P55772 traces to PMID:17502665: intact-cell phosphate release, CD39-null comparison, surface staining and ADP TLC in Results/Fig3 with Methods sec12–13. The original is mouse T-cell work, not a published human replication. Independent human endothelial intact-cell hydrolysis and surface CD39 corroborate transfer to ENTPD1. No extracellular-matrix localization is inferred. Evidence: PMID17502665 https://pmc.ncbi.nlm.nih.gov/articles/PMC2118603/, Fig3 and Methodssec12–13; PMID8996251 Methodssec8/Resultssec22 (https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P55772 SUPPORTS TRANSFER Mouse Entpd1 donor and original PMID17502665 verified; surface CD39 and CD39-dependent ADP hydrolysis support transfer, independently corroborated in human. ensembl:ENSMUSP00000107850 SUPPORTS TRANSFER Mouse Entpd1 donor and original PMID17502665 verified; surface CD39 and CD39-dependent ADP hydrolysis support transfer, independently corroborated in human. |
| GO:0016020 membrane | EXP PMID:10636909 Palmitoylation targets CD39/endothelial ATP diphosphohydrola... | MODIFY | Summary: Refine membrane to plasma membrane. Reason: PMID:10636909 Figures 4–5 support the already annotated plasma-membrane location. Original: https://doi.org/10.1074/jbc.275.3.2057 (Experimental Procedures and localization Results/Figures4–5). Proposed replacements: plasma membrane Supporting Evidence: |
| GO:0016020 membrane | EXP PMID:8955160 Identification and characterization of CD39/vascular ATP dip... | MODIFY | Summary: Human CD39 is localized to the plasma membrane. Reason: PMID:8955160 is abstract-only in the reviewed access set. Independently, PMID:10636909 Experimental Procedures (Cell Culture, Enzyme Cytochemistry and Immunostaining) and Results (Electron Microscopy and Cytochemistry; Figs4–5) identify native human HUVEC surface CD39 and human CD39 expressed in COS-7 cells. PMID:8996251 sec22/Fig5 also detects surface CD39 in human endothelial cells. These inspected originals establish the plasma-membrane location; they do not identify all natural products or reverify the unread 1996 assay. https://doi.org/10.1074/jbc.275.3.2057; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/. Proposed replacements: plasma membrane |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MODIFY | Summary: The broad membrane location can be refined to the independently established plasma membrane. Reason: PMID:19946888 reports high-throughput analysis of YTS NK-like-cell membrane fractions in its accessible abstract. Its full article and ENTPD1-specific entry in jms1696_Suppinfotable1.xls were not recovered, so the original proteomic identification is not independently reverified here. Plasma-membrane localization is nevertheless established by PMID:10636909: native human HUVEC immunostaining and enzyme cytochemistry in Results/Figure 5A–B, and recombinant human CD39 in COS-7 cells in Figure 4B. GO:0005886 is a current is_a child of GO:0016020 and is already represented by the existing plasma-membrane annotations, including the PMID:7930580 row. Refine the broad term using that independent evidence; this does not relabel the YTS preparation itself as a purified plasma-membrane fraction. Public originals: https://doi.org/10.1002/jms.1696; https://doi.org/10.1074/jbc.275.3.2057. See ENTPD1-reference-guide.md for access limits. Proposed replacements: plasma membrane |
| GO:0016020 membrane | IEA GO_REF:0000044 | MODIFY | Summary: The mapped membrane location can be specified as plasma membrane. Reason: SL-0162 supports the broad membrane mapping. Human intact-cell enzyme assays, surface CD39 staining and the resolved Reactome catalyst establish the more informative plasma-membrane location. This does not assign every alternative product the same topology. Evidence: PMID8996251 sec22/Fig5 (https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/); mapping https://rest.uniprot.org/locations/SL-0162.json. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-SubCell:SL-0162 SUPPORTS TRANSFER Official location-to-GO mapping verified; target experimental location and the scope of the refinement are assessed separately. Proposed replacements: plasma membrane |
| GO:0016787 hydrolase activity | IEA GO_REF:0000002 | MODIFY | Summary: The GDA1/CD39 family hydrolase mapping can be refined to apyrase activity. Reason: InterPro IPR000407 is the official nucleoside-phosphatase GDA1/CD39 family and legitimately maps broad hydrolase activity. Human ATP and ADP hydrolysis support the more informative GO:0004050 apyrase activity. The family mapping is not erroneous; the refinement uses target experiments. Evidence: InterPro https://www.ebi.ac.uk/interpro/entry/InterPro/IPR000407/; PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR000407 SUPPORTS TRANSFER Official GDA1/CD39 nucleoside-phosphatase family maps hydrolase activity. Target experiments permit apyrase refinement. Proposed replacements: apyrase activity |
| GO:0016887 ATP hydrolysis activity | EXP PMID:8529670 Purification and properties of human placental ATP diphospho... | ACCEPT | Summary: Purified human placental ATP diphosphohydrolase hydrolyzes ATP. Reason: Table 3 measures phosphate release with ATP; the purified preparation lacks detectable monophosphate and nonspecific alkaline-phosphatase activity. Methods and Fig. 4 establish divalent-cation-dependent catalysis. This supports ATP hydrolysis activity as substrate chemistry, without assigning equal activity to all natural products. See PMID:8529670, pp.67,70–71, Enzymic assays, Fig.2, Fig.4 and Table3; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1995.066_c.x. Supporting Evidence: |
| GO:0016887 ATP hydrolysis activity | EXP PMID:8626624 CD39 is an ecto-(Ca2+,Mg2+)-apyrase. | ACCEPT | Summary: Human CD39 confers extracellular ATP-hydrolyzing activity in COS-7 cells. Reason: The accessible original Methods measure terminal-phosphate release from ATP; Results establish Ca2+/Mg2+-dependent activity in intact human LG2 cells and increased Ca2+-ATPase activity after human CD39 expression in COS-7 cells. ATP is a ribonucleoside triphosphate, supporting this catalytic term without requiring unobserved alternative-substrate results. See PMID:8626624, Assay of Apyrase Activity, initial Results and Demonstration of CD39 as an Ecto-apyrase (partial); https://www.sciencedirect.com/science/article/pii/S0021925817310347. Correct DOI is 10.1074/jbc.271.17.9898; the conflicting Europe PMC DOI is a metadata defect. Supporting Evidence: |
| GO:0016887 ATP hydrolysis activity | EXP PMID:8955160 Identification and characterization of CD39/vascular ATP dip... | ACCEPT | Summary: Independent original human enzyme measurements support ATP hydrolysis activity. Reason: PMID:8955160 was verified by PubMed/publisher metadata and abstract; operative full text remains inaccessible. The biological claim is nevertheless established independently by PMID:8529670, Materials and Methods (Enzymic assays) and Table3 p71: purified human placental enzyme hydrolyzes ATP with phosphate release. The enzyme preparation was not isoform resolved, so no activity is assigned equally to all six natural products. This accepts the supported whole-gene activity without claiming the unread portion of the original citation was verified. Original: https://doi.org/10.1111/j.1432-1033.1995.066_c.x. Independent intact human/pig endothelial assays also support ATP/ADP hydrolysis (PMID:8996251 Methods sec8 and Results sec20/Fig2; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/); pig TLC and human-cell observations remain distinct. |
| GO:0016887 ATP hydrolysis activity | EXP PMID:8996251 Loss of ATP diphosphohydrolase activity with endothelial cel... | ACCEPT | Summary: Endothelial ATPDase hydrolyzes extracellular ATP and ADP with inorganic phosphate release. Reason: Methods assay intact human and porcine EC with ATP or ADP and quantify inorganic phosphate. Results establish divalent-cation-dependent ATPDase activity; porcine Fig.2 resolves ADP conversion to AMP. Human surface CD39 is demonstrated in Fig.5. Together these support ATP hydrolysis activity; ATP and ADP instantiate the broader nucleotide classes, without claiming every nucleotide or every isoform was tested. Adenosine appears downstream through a separate 5-prime-nucleotidase step, not ENTPD1 monophosphatase activity. See PMID:8996251, sec8 Methods, sec20 Results/Fig.2 and sec22/Fig.5; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/. Supporting Evidence: |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: Independent Rhea and human experiments support ATP hydrolysis. Reason: RHEA:13065 is ATP to ADP plus inorganic phosphate, corroborated by human placental and recombinant CD39 experiments. Current ARBA00043426 has no condition set matched by the captured target FunFam/InterPro/taxon records; that current-rule discrepancy is recorded separately and does not invalidate the independent Rhea route or the biological function. Evidence: Rhea https://www.rhea-db.org/rhea/13065; rule https://rest.uniprot.org/arba/ARBA00043426.json; PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00043426 UNRESOLVED Current rule retrieved, but none of its condition sets matches the captured target FunFam/InterPro/taxon entries. Epoch mismatch is possible; independent Rhea/human ATP evidence supports the term. RHEA:13065 SUPPORTS TRANSFER ATP + H2O = ADP + phosphate + H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. |
| GO:0017110 nucleoside diphosphate phosphatase activity | IDA PMID:10636909 Palmitoylation targets CD39/endothelial ATP diphosphohydrola... | ACCEPT | Summary: The nucleotide-class phosphatase activity is supported by complementary human substrate assays. Reason: PMID:10636909 ATPDase Assays and Results/Figs4–5 use ADP and support the imported catalytic class. The broader class is also independently established by PMID:8529670 Table3, measuring ADP, GDP and IDP with purified human placental enzyme. A single-substrate experiment does not require narrowing the whole-gene class when multiple substrates are directly supported. No claim of uniform kinetics, every possible nucleotide substrate or equal function of all products is made. https://doi.org/10.1074/jbc.275.3.2057; https://doi.org/10.1111/j.1432-1033.1995.066_c.x. |
| GO:0017110 nucleoside diphosphate phosphatase activity | IDA PMID:8529670 Purification and properties of human placental ATP diphospho... | ACCEPT | Summary: Purified human placental ATP diphosphohydrolase hydrolyzes ADP, GDP and IDP. Reason: Table 3 measures phosphate release with ADP, GDP and IDP; the purified preparation lacks detectable monophosphate and nonspecific alkaline-phosphatase activity. Methods and Fig. 4 establish divalent-cation-dependent catalysis. This supports nucleoside diphosphate phosphatase activity as substrate chemistry, without assigning equal activity to all natural products. See PMID:8529670, pp.67,70–71, Enzymic assays, Fig.2, Fig.4 and Table3; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1995.066_c.x. Supporting Evidence: |
| GO:0017110 nucleoside diphosphate phosphatase activity | IDA PMID:8626624 CD39 is an ecto-(Ca2+,Mg2+)-apyrase. | ACCEPT | Summary: Independent original human enzyme measurements support nucleoside diphosphate phosphatase activity. Reason: Only Methods, part of Results and Discussion were recovered for PMID:8626624; its full substrate table remains inaccessible. The biological claim is nevertheless established independently by PMID:8529670, Materials and Methods (Enzymic assays) and Table3 p71: purified human placental enzyme hydrolyzes ADP, GDP and IDP with phosphate release. The enzyme preparation was not isoform resolved, so no activity is assigned equally to all six natural products. This accepts the supported whole-gene activity without claiming the unread portion of the original citation was verified. Original: https://doi.org/10.1111/j.1432-1033.1995.066_c.x. Independent intact human/pig endothelial assays also support ATP/ADP hydrolysis (PMID:8996251 Methods sec8 and Results sec20/Fig2; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/); pig TLC and human-cell observations remain distinct. |
| GO:0017110 nucleoside diphosphate phosphatase activity | IDA PMID:8955160 Identification and characterization of CD39/vascular ATP dip... | ACCEPT | Summary: Independent original human enzyme measurements support nucleoside diphosphate phosphatase activity. Reason: PMID:8955160 was verified by PubMed/publisher metadata and abstract; operative full text remains inaccessible. The biological claim is nevertheless established independently by PMID:8529670, Materials and Methods (Enzymic assays) and Table3 p71: purified human placental enzyme hydrolyzes ADP, GDP and IDP with phosphate release. The enzyme preparation was not isoform resolved, so no activity is assigned equally to all six natural products. This accepts the supported whole-gene activity without claiming the unread portion of the original citation was verified. Original: https://doi.org/10.1111/j.1432-1033.1995.066_c.x. Independent intact human/pig endothelial assays also support ATP/ADP hydrolysis (PMID:8996251 Methods sec8 and Results sec20/Fig2; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/); pig TLC and human-cell observations remain distinct. |
| GO:0017110 nucleoside diphosphate phosphatase activity | IDA PMID:8996251 Loss of ATP diphosphohydrolase activity with endothelial cel... | ACCEPT | Summary: Endothelial ATPDase hydrolyzes extracellular ATP and ADP with inorganic phosphate release. Reason: Methods assay intact human and porcine EC with ATP or ADP and quantify inorganic phosphate. Results establish divalent-cation-dependent ATPDase activity; porcine Fig.2 resolves ADP conversion to AMP. Human surface CD39 is demonstrated in Fig.5. Together these support nucleoside diphosphate phosphatase activity; ATP and ADP instantiate the broader nucleotide classes, without claiming every nucleotide or every isoform was tested. Adenosine appears downstream through a separate 5-prime-nucleotidase step, not ENTPD1 monophosphatase activity. See PMID:8996251, sec8 Methods, sec20 Results/Fig.2 and sec22/Fig.5; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/. Supporting Evidence: |
| GO:0017110 nucleoside diphosphate phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: ENTPD1 hydrolyzes nucleoside diphosphates to monophosphates. Reason: RHEA:36799 gives the appropriate class reaction. The correct mouse ortholog retains NDP hydrolysis, and human Table3 directly measures ADP, GDP and IDP. Preserve the broad class rather than narrowing the enzyme to the one substrate used in a particular interaction experiment. Evidence: Rhea https://www.rhea-db.org/rhea/36799; PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P55772 SUPPORTS TRANSFER P55772 is mouse Entpd1 in PTHR11782:SF32. Human substrate assays independently support the transferred catalytic class. ensembl:ENSMUSP00000107850 SUPPORTS TRANSFER P55772 is mouse Entpd1 in PTHR11782:SF32. Human substrate assays independently support the transferred catalytic class. RHEA:36799 SUPPORTS TRANSFER a ribonucleoside 5'-diphosphate + H2O = a ribonucleoside 5'-phosphate + phosphate + H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. |
| GO:0017111 ribonucleoside triphosphate phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited ribonucleoside-triphosphate phosphatase activity is retained. Reason: The actual Opisthokonta IBD node includes human ENTPD1, with independent target ATP/GTP/ITP/CTP assays. Target self-donor evidence is expected and valid; no function-loss assertion on the target path was recovered. PANTHER PTHR11782 target PTN002483056 descends from PTN000207579; the pinned IBD row exactly matches the imported donor set and no NOT record for this term appears on the target path. Current MSA ungapped target sequence matches P49961 exactly. Evidence: PAINT PTHR11782/PTN000207579 (https://www.pantherdb.org/panther/family.do?clsAccession=PTHR11782); PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000207579 SUPPORTS TRANSFER Actual IBD at PTN000207579 and matching donor set recovered; P49961 descends from this node with no term-specific target-path NOT. Self-donor presence is valid experimental grounding where present. |
| GO:0017111 ribonucleoside triphosphate phosphatase activity | IDA PMID:10636909 Palmitoylation targets CD39/endothelial ATP diphosphohydrola... | ACCEPT | Summary: The nucleotide-class phosphatase activity is supported by complementary human substrate assays. Reason: PMID:10636909 ATPDase Assays and Results/Figs4–5 use ATP and support the imported catalytic class. The broader class is also independently established by PMID:8529670 Table3, measuring ATP, GTP, ITP and CTP with purified human placental enzyme. A single-substrate experiment does not require narrowing the whole-gene class when multiple substrates are directly supported. No claim of uniform kinetics, every possible nucleotide substrate or equal function of all products is made. https://doi.org/10.1074/jbc.275.3.2057; https://doi.org/10.1111/j.1432-1033.1995.066_c.x. |
| GO:0017111 ribonucleoside triphosphate phosphatase activity | IDA PMID:8529670 Purification and properties of human placental ATP diphospho... | ACCEPT | Summary: Purified human placental ATP diphosphohydrolase hydrolyzes ATP, GTP, ITP and CTP. Reason: Table 3 measures phosphate release with ATP, GTP, ITP and CTP; the purified preparation lacks detectable monophosphate and nonspecific alkaline-phosphatase activity. Methods and Fig. 4 establish divalent-cation-dependent catalysis. This supports ribonucleoside triphosphate phosphatase activity as substrate chemistry, without assigning equal activity to all natural products. See PMID:8529670, pp.67,70–71, Enzymic assays, Fig.2, Fig.4 and Table3; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1995.066_c.x. Supporting Evidence: |
| GO:0017111 ribonucleoside triphosphate phosphatase activity | IDA PMID:8626624 CD39 is an ecto-(Ca2+,Mg2+)-apyrase. | ACCEPT | Summary: Human CD39 confers extracellular ATP-hydrolyzing activity in COS-7 cells. Reason: The accessible original Methods measure terminal-phosphate release from ATP; Results establish Ca2+/Mg2+-dependent activity in intact human LG2 cells and increased Ca2+-ATPase activity after human CD39 expression in COS-7 cells. ATP is a ribonucleoside triphosphate, supporting this catalytic term without requiring unobserved alternative-substrate results. See PMID:8626624, Assay of Apyrase Activity, initial Results and Demonstration of CD39 as an Ecto-apyrase (partial); https://www.sciencedirect.com/science/article/pii/S0021925817310347. Correct DOI is 10.1074/jbc.271.17.9898; the conflicting Europe PMC DOI is a metadata defect. Supporting Evidence: |
| GO:0017111 ribonucleoside triphosphate phosphatase activity | IDA PMID:8955160 Identification and characterization of CD39/vascular ATP dip... | ACCEPT | Summary: Independent original human enzyme measurements support ribonucleoside triphosphate phosphatase activity. Reason: PMID:8955160 was verified by PubMed/publisher metadata and abstract; operative full text remains inaccessible. The biological claim is nevertheless established independently by PMID:8529670, Materials and Methods (Enzymic assays) and Table3 p71: purified human placental enzyme hydrolyzes ATP, GTP, ITP and CTP with phosphate release. The enzyme preparation was not isoform resolved, so no activity is assigned equally to all six natural products. This accepts the supported whole-gene activity without claiming the unread portion of the original citation was verified. Original: https://doi.org/10.1111/j.1432-1033.1995.066_c.x. Independent intact human/pig endothelial assays also support ATP/ADP hydrolysis (PMID:8996251 Methods sec8 and Results sec20/Fig2; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/); pig TLC and human-cell observations remain distinct. |
| GO:0017111 ribonucleoside triphosphate phosphatase activity | IDA PMID:8996251 Loss of ATP diphosphohydrolase activity with endothelial cel... | ACCEPT | Summary: Endothelial ATPDase hydrolyzes extracellular ATP and ADP with inorganic phosphate release. Reason: Methods assay intact human and porcine EC with ATP or ADP and quantify inorganic phosphate. Results establish divalent-cation-dependent ATPDase activity; porcine Fig.2 resolves ADP conversion to AMP. Human surface CD39 is demonstrated in Fig.5. Together these support ribonucleoside triphosphate phosphatase activity; ATP and ADP instantiate the broader nucleotide classes, without claiming every nucleotide or every isoform was tested. Adenosine appears downstream through a separate 5-prime-nucleotidase step, not ENTPD1 monophosphatase activity. See PMID:8996251, sec8 Methods, sec20 Results/Fig.2 and sec22/Fig.5; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/. Supporting Evidence: |
| GO:0017111 ribonucleoside triphosphate phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Rhea and orthology support ribonucleoside-triphosphate phosphatase activity. Reason: The generic RHEA:23680 reaction is independently supported by human ATP/GTP/ITP/CTP turnover and the correct mouse ortholog. RHEA:64900 specifically denotes UTP hydrolysis and traces to rat similarity; that substrate-specific route is less directly verified here. Acceptance of the class term does not claim that every listed substrate route was experimentally checked in human. Evidence: Rhea https://www.rhea-db.org/rhea/23680 and https://www.rhea-db.org/rhea/64900; PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P55772 SUPPORTS TRANSFER P55772 is mouse Entpd1 in PTHR11782:SF32. Human substrate assays independently support the transferred catalytic class. ensembl:ENSMUSP00000107850 SUPPORTS TRANSFER P55772 is mouse Entpd1 in PTHR11782:SF32. Human substrate assays independently support the transferred catalytic class. RHEA:23680 SUPPORTS TRANSFER a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. RHEA:64900 SOURCE WEAK OR INFERRED UTP + H2O = UDP + phosphate + H(+). Human record is inferred from rat P97687; operative rat UTP result not recovered here. |
| GO:0017111 ribonucleoside triphosphate phosphatase activity | ISS GO_REF:0000024 | ACCEPT | Summary: The correct rat ENTPD1 ortholog supports the broad NTP-phosphatase function. Reason: P97687 is rat Entpd1 in the same ENTPD1 subfamily, not another NTPDase paralog. Its curated reaction record and the accessible original PMID:22100451 introduction describe ATPase assays of an engineered rat ectodomain. The full original substrate table was not recovered. Human ATP/GTP/ITP/CTP experiments independently support this broad term, so acceptance does not depend on unseen rat alternative-substrate measurements. Evidence: Rat https://www.uniprot.org/uniprotkb/P97687/entry; PMID22100451 https://doi.org/10.1016/j.jmb.2011.10.050 (partial original); PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P97687 SUPPORTS TRANSFER Rat Entpd1 identity and ENTPD1 subfamily verified. PMID22100451 original only partly accessible; human NTP assays independently establish the broad target activity. |
| GO:0036384 CDP phosphatase activity | IEA GO_REF:0000116 | UNDECIDED | Summary: The CDP-specific reaction is mapped correctly, but direct substrate support is unresolved. Reason: RHEA:64880 means CDP to CMP plus inorganic phosphate. Target UniProt attaches ECO:0000305 to this reaction and ECO:0000269 to its physiological direction with PMID:8529670. The original Table3 tests ADP/GDP/IDP but not CDP; CTP hydrolysis alone does not establish the subsequent CDP step. This does not refute CDP activity or invalidate the citation: the source is partly curatorial inference and another unrecovered assay might resolve it. Retain unresolved status rather than converting class specificity into a measured CDP result. Evidence: Rhea https://www.rhea-db.org/rhea/64880; human UniProt https://www.uniprot.org/uniprotkb/P49961/entry catalytic evidence; PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: UNRESOLVED Sources checked: RHEA:64880 UNRESOLVED CDP + H2O = CMP + phosphate + H(+). Chemistry matches the term; source-specific substrate evidence is incompletely adjudicated. |
| GO:0043262 ADP phosphatase activity | EXP PMID:8529670 Purification and properties of human placental ATP diphospho... | ACCEPT | Summary: Purified human placental ATP diphosphohydrolase hydrolyzes ADP. Reason: Table 3 measures phosphate release with ADP; the purified preparation lacks detectable monophosphate and nonspecific alkaline-phosphatase activity. Methods and Fig. 4 establish divalent-cation-dependent catalysis. This supports ADP phosphatase activity as substrate chemistry, without assigning equal activity to all natural products. See PMID:8529670, pp.67,70–71, Enzymic assays, Fig.2, Fig.4 and Table3; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1995.066_c.x. Supporting Evidence: |
| GO:0043262 ADP phosphatase activity | EXP PMID:8626624 CD39 is an ecto-(Ca2+,Mg2+)-apyrase. | ACCEPT | Summary: Independent original human enzyme measurements support ADP phosphatase activity. Reason: Only Methods, part of Results and Discussion were recovered for PMID:8626624; its full substrate table remains inaccessible. The biological claim is nevertheless established independently by PMID:8529670, Materials and Methods (Enzymic assays) and Table3 p71: purified human placental enzyme hydrolyzes ADP with phosphate release. The enzyme preparation was not isoform resolved, so no activity is assigned equally to all six natural products. This accepts the supported whole-gene activity without claiming the unread portion of the original citation was verified. Original: https://doi.org/10.1111/j.1432-1033.1995.066_c.x. Independent intact human/pig endothelial assays also support ATP/ADP hydrolysis (PMID:8996251 Methods sec8 and Results sec20/Fig2; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/); pig TLC and human-cell observations remain distinct. |
| GO:0043262 ADP phosphatase activity | EXP PMID:8955160 Identification and characterization of CD39/vascular ATP dip... | ACCEPT | Summary: Independent original human enzyme measurements support ADP phosphatase activity. Reason: PMID:8955160 was verified by PubMed/publisher metadata and abstract; operative full text remains inaccessible. The biological claim is nevertheless established independently by PMID:8529670, Materials and Methods (Enzymic assays) and Table3 p71: purified human placental enzyme hydrolyzes ADP with phosphate release. The enzyme preparation was not isoform resolved, so no activity is assigned equally to all six natural products. This accepts the supported whole-gene activity without claiming the unread portion of the original citation was verified. Original: https://doi.org/10.1111/j.1432-1033.1995.066_c.x. Independent intact human/pig endothelial assays also support ATP/ADP hydrolysis (PMID:8996251 Methods sec8 and Results sec20/Fig2; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/); pig TLC and human-cell observations remain distinct. |
| GO:0043262 ADP phosphatase activity | EXP PMID:8996251 Loss of ATP diphosphohydrolase activity with endothelial cel... | ACCEPT | Summary: Endothelial ATPDase hydrolyzes extracellular ATP and ADP with inorganic phosphate release. Reason: Methods assay intact human and porcine EC with ATP or ADP and quantify inorganic phosphate. Results establish divalent-cation-dependent ATPDase activity; porcine Fig.2 resolves ADP conversion to AMP. Human surface CD39 is demonstrated in Fig.5. Together these support ADP phosphatase activity; ATP and ADP instantiate the broader nucleotide classes, without claiming every nucleotide or every isoform was tested. Adenosine appears downstream through a separate 5-prime-nucleotidase step, not ENTPD1 monophosphatase activity. See PMID:8996251, sec8 Methods, sec20 Results/Fig.2 and sec22/Fig.5; https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/. Supporting Evidence: |
| GO:0043262 ADP phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: ADP hydrolysis has independent human experimental and Rhea support. Reason: RHEA:61436 is ADP to AMP plus inorganic phosphate; human placental and endothelial originals establish this chemistry. The correct mouse ortholog supplies a second transfer route. ARBA00086495 currently returns 404; the missing current rule does not negate these independent routes. Evidence: Rhea https://www.rhea-db.org/rhea/61436; PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x); PMID8996251 sec20/Fig2 (https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/). Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00086495 SOURCE STALE OR MISSING Current official endpoint returns404; historical rule content was not recovered. Independent routes are evaluated separately. UniProtKB:P55772 SUPPORTS TRANSFER P55772 is mouse Entpd1 in PTHR11782:SF32. Human substrate assays independently support the transferred catalytic class. ensembl:ENSMUSP00000107850 SUPPORTS TRANSFER P55772 is mouse Entpd1 in PTHR11782:SF32. Human substrate assays independently support the transferred catalytic class. RHEA:61436 SUPPORTS TRANSFER ADP + H2O = AMP + phosphate + H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. |
| GO:0043273 CTPase activity | EXP PMID:8529670 Purification and properties of human placental ATP diphospho... | ACCEPT | Summary: Purified human placental ATP diphosphohydrolase hydrolyzes CTP. Reason: Table 3 measures phosphate release with CTP; the purified preparation lacks detectable monophosphate and nonspecific alkaline-phosphatase activity. Methods and Fig. 4 establish divalent-cation-dependent catalysis. This supports CTPase activity as substrate chemistry, without assigning equal activity to all natural products. See PMID:8529670, pp.67,70–71, Enzymic assays, Fig.2, Fig.4 and Table3; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1995.066_c.x. Supporting Evidence: |
| GO:0043273 CTPase activity | EXP PMID:8626624 CD39 is an ecto-(Ca2+,Mg2+)-apyrase. | ACCEPT | Summary: Independent original human enzyme measurements support CTPase activity. Reason: Only Methods, part of Results and Discussion were recovered for PMID:8626624; its full substrate table remains inaccessible. The biological claim is nevertheless established independently by PMID:8529670, Materials and Methods (Enzymic assays) and Table3 p71: purified human placental enzyme hydrolyzes CTP with phosphate release. The enzyme preparation was not isoform resolved, so no activity is assigned equally to all six natural products. This accepts the supported whole-gene activity without claiming the unread portion of the original citation was verified. Original: https://doi.org/10.1111/j.1432-1033.1995.066_c.x. |
| GO:0043273 CTPase activity | IEA GO_REF:0000116 | ACCEPT | Summary: The mapped CTP hydrolysis reaction agrees with human substrate measurements. Reason: RHEA:29387 converts CTP to CDP plus inorganic phosphate. Human placental Table3 measures CTP hydrolysis. This supports CTPase activity without additionally treating the untested CDP substrate as directly measured. Evidence: Rhea https://www.rhea-db.org/rhea/29387; PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:29387 SUPPORTS TRANSFER CTP + H2O = CDP + phosphate + H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. |
| GO:0045134 UDP phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT ancestral UDP-phosphatase assertion is retained for ENTPD1. Reason: The verified PTN000207579 IBD places UDP-phosphatase activity in the inherited Opisthokonta clade, and the target lies within that clade with no target-path loss annotation or target-specific contrary evidence identified. This is a phylogenetic curator judgment supported by its full descendant evidence set, not a pairwise transfer requiring the single rat paper to stand alone. The rat-specific original remains partially inaccessible; no human UDP assay is claimed. PANTHER PTHR11782 target PTN002483056 descends from PTN000207579; the pinned IBD row exactly matches the imported donor set and no NOT record for this term appears on the target path. Current MSA ungapped target sequence matches P49961 exactly. Evidence: PAINT PTHR11782/PTN000207579 (https://www.pantherdb.org/panther/family.do?clsAccession=PTHR11782), IBD GO0045134; rat PMID22100451 https://doi.org/10.1016/j.jmb.2011.10.050 (partial original). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000207579 SUPPORTS TRANSFER Actual IBD at PTN000207579 and matching donor set recovered; P49961 descends from this node with no term-specific target-path NOT. Self-donor presence is valid experimental grounding where present. |
| GO:0045134 UDP phosphatase activity | IEA GO_REF:0000116 | UNDECIDED | Summary: The UDP-specific Rhea chemistry is correct, but the target evidence chain remains incompletely adjudicated. Reason: RHEA:64876 is UDP to UMP plus inorganic phosphate. Target UniProt infers this from rat P97687, whose experimental record cites PMID:22100451. Only the original abstract, introduction and short section snippets were accessible, not operative UDP methods/results. This narrower source-specific route remains unresolved despite the independent PAINT ancestral assertion; there is no evidence here that UDP hydrolysis is absent. Evidence: Rhea https://www.rhea-db.org/rhea/64876; rat UniProt https://www.uniprot.org/uniprotkb/P97687/entry; PMID22100451 https://doi.org/10.1016/j.jmb.2011.10.050 (operative UDP assay unavailable). Propagation Review Root cause: UNRESOLVED Sources checked: RHEA:64876 UNRESOLVED UDP + H2O = UMP + phosphate + H(+). Chemistry matches the term; source-specific substrate evidence is incompletely adjudicated. |
| GO:0045134 UDP phosphatase activity | ISS GO_REF:0000024 | UNDECIDED | Summary: The rat ortholog is correct, but its cited UDP experiment was not recovered. Reason: P97687 is rat Entpd1 in the same ENTPD1 subfamily and currently carries experimental UDP-phosphatase annotation to PMID:22100451. The accessible original concerns engineered rat ectodomains; its operative UDP substrate assay remains inaccessible. This source-specific transfer therefore remains unresolved, without claiming wrong paralog, absent UDP activity or equivalence to any human natural product. Evidence: Rat UniProt https://www.uniprot.org/uniprotkb/P97687/entry; PMID22100451 https://doi.org/10.1016/j.jmb.2011.10.050 (operative UDP assay unavailable). Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P97687 UNRESOLVED Rat Entpd1 identity and ENTPD1 subfamily verified. PMID22100451 original only partly accessible; UDP-specific operative assay remains unread. |
| GO:0046032 ADP catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: ENTPD1 directly catalyzes extracellular ADP degradation. Reason: Mouse P55772 traces to PMID:17502665: CD39-null T cells show impaired ADP phosphohydrolysis in Fig3 with TLC Methods sec13. Human placental/endothelial experiments independently support ADP to AMP. CD39 performs the ADP degradation step; CD73 supplies the subsequent AMP-to-adenosine step, so this does not assign ENTPD1 adenosine-forming AMPase activity. Evidence: PMID17502665 https://pmc.ncbi.nlm.nih.gov/articles/PMC2118603/, Fig3/Methodssec13; PMID8996251 sec20/Fig2 (https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P55772 SUPPORTS TRANSFER Mouse Entpd1 donor and original PMID17502665 verified; surface CD39 and CD39-dependent ADP hydrolysis support transfer, independently corroborated in human. ensembl:ENSMUSP00000107850 SUPPORTS TRANSFER Mouse Entpd1 donor and original PMID17502665 verified; surface CD39 and CD39-dependent ADP hydrolysis support transfer, independently corroborated in human. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | UNDECIDED | Summary: The original human B-cell exosome purification and proteomics methods were read, but the ENTPD1-specific supplementary identification remains inaccessible. Reason: PMID:20458337, Results (Identification of exosomal proteins), Figure 1 and Methods (Cell culture and exosome isolation, Mass spectrometry, MS data analysis), describes differential centrifugation, sucrose flotation and anti-MHC-II capture of exosomes from human RN B cells. The whole-exosome list is Supplementary Table 1, with at least two unique peptides in at least two of three independent experiments. The ENTPD1/CD39 identifier and peptide entry in that table were not recovered; the accessible article body does not individually identify ENTPD1. Keep the source-specific localization unresolved rather than reject the experimental annotation. The separate MHC-II co-immunoprecipitation experiment and main Table 1 do not establish an ENTPD1 interaction or a role in exosome biogenesis. Public originals: https://doi.org/10.1038/icb.2010.64. See ENTPD1-reference-guide.md for access limits. Supporting Evidence: |
| GO:0070527 platelet aggregation | IMP PMID:8955160 Identification and characterization of CD39/vascular ATP dip... | MODIFY | Summary: Extracellular ADP hydrolysis negatively regulates platelet aggregation. Reason: PMID:8955160 is correctly identified but its operative full text was not recovered. Independently read PMID:8996251 Methods and Results sec19/Fig1 establish inhibition of human platelet aggregation by human and porcine endothelial cells; inhibition is lost for nonhydrolyzable ADP-beta-S, connecting the effect to extracellular nucleotide hydrolysis. Negative regulation of platelet aggregation captures this demonstrated enzymatic contribution more precisely than the imported platelet aggregation term. This is refinement using independent original evidence, not an assertion that the unread experimental citation is wrong. See https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/, sec19/Fig1. Proposed replacements: negative regulation of platelet aggregation |
| GO:0070527 platelet aggregation | IMP PMID:8996251 Loss of ATP diphosphohydrolase activity with endothelial cel... | MODIFY | Summary: Endothelial ATPDase suppresses platelet aggregation by removing extracellular ADP. Reason: Human and porcine EC inhibit human platelet aggregation; the nonhydrolyzable ADP-beta-S control loses this inhibition, supporting the enzyme’s catalytic contribution to negative regulation. The specific regulatory term describes the demonstrated function more accurately than platelet aggregation itself. See PMID:8996251, sec19 Results and Fig.1 (indexed blocks51–56); https://pmc.ncbi.nlm.nih.gov/articles/PMC2196106/. Human and pig EC observations are distinguished from the rat kidney experiment. Proposed replacements: negative regulation of platelet aggregation Supporting Evidence: |
| GO:0103023 ITPase activity | EXP PMID:8529670 Purification and properties of human placental ATP diphospho... | ACCEPT | Summary: Purified human placental ATP diphosphohydrolase hydrolyzes ITP. Reason: Table 3 measures phosphate release with ITP; the purified preparation lacks detectable monophosphate and nonspecific alkaline-phosphatase activity. Methods and Fig. 4 establish divalent-cation-dependent catalysis. This supports ITPase activity as substrate chemistry, without assigning equal activity to all natural products. See PMID:8529670, pp.67,70–71, Enzymic assays, Fig.2, Fig.4 and Table3; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1995.066_c.x. Supporting Evidence: |
| GO:0103023 ITPase activity | IEA GO_REF:0000116 | ACCEPT | Summary: ITP hydrolysis is supported by the mapped reaction and human substrate assay. Reason: RHEA:28330 converts ITP to IDP plus inorganic phosphate. Human placental Table3 directly measures ITP turnover; this does not imply a signaling or transport activity. Evidence: Rhea https://www.rhea-db.org/rhea/28330; PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:28330 SUPPORTS TRANSFER ITP + H2O = IDP + phosphate + H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. |
| GO:1990003 IDP phosphatase activity | EXP PMID:8529670 Purification and properties of human placental ATP diphospho... | ACCEPT | Summary: Purified human placental ATP diphosphohydrolase hydrolyzes IDP. Reason: Table 3 measures phosphate release with IDP; the purified preparation lacks detectable monophosphate and nonspecific alkaline-phosphatase activity. Methods and Fig. 4 establish divalent-cation-dependent catalysis. This supports IDP phosphatase activity as substrate chemistry, without assigning equal activity to all natural products. See PMID:8529670, pp.67,70–71, Enzymic assays, Fig.2, Fig.4 and Table3; https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1995.066_c.x. Supporting Evidence: |
| GO:1990003 IDP phosphatase activity | IEA GO_REF:0000116 | ACCEPT | Summary: IDP hydrolysis is supported by the mapped reaction and human substrate assay. Reason: RHEA:35207 converts IDP to IMP plus inorganic phosphate. Human placental Table3 directly measures IDP turnover, while monophosphate substrates were inactive. Evidence: Rhea https://www.rhea-db.org/rhea/35207; PMID8529670 Table3 (https://doi.org/10.1111/j.1432-1033.1995.066_c.x). Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:35207 SUPPORTS TRANSFER IDP + H2O = IMP + phosphate + H(+). Target human nucleotide-hydrolysis evidence supports this reaction class or substrate; see reason for assay scope. |
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Download this section (compressed HTML)Q: In the antibody-induced homotypic B-cell adhesion reported in the abstract of PMID:7930580, does CD39 participate in adhesive contact or alter adhesion through extracellular nucleotide metabolism and purinergic signaling? The operative historical assay remains inaccessible; this is an unresolved mechanism in the reviewed evidence, not a claim that no later study has addressed it.
Q: What are the product-resolved CDP-to-CMP and UDP-to-UMP rates of human CD39 under matched substrate and divalent-cation conditions? PMID:8529670 Table 3 does not test these diphosphates, and the operative rat UDP assay in PMID:22100451 remains unread; PAINT supports inherited UDP activity but does not supply a measured human rate or establish equivalence of all six natural products.
Q: For ENTPD1, should GO:0003924 GTPase activity continue to represent the GTP-to-GDP-plus-phosphate chemistry measured in PMID:8529670 Table 3, or should ontology guidance distinguish this ectonucleotidase chemistry from signaling and translation GTPases while retaining the established nucleoside-triphosphatase activity? No signaling-switch mechanism is inferred.
Experiment: After recovering and reproducing the PMID:7930580 adhesion conditions, compare matched human B-cell systems expressing wild-type CD39 or a catalytically inactive construct whose surface expression and antibody binding are verified. Measure cell-contact formation and extracellular ATP/ADP/AMP in parallel, with matched antibody-crosslinking controls and purinergic-receptor or CD73 perturbations. Treat engineered constructs separately from natural products; this design distinguishes candidate mechanisms rather than asserting a direct adhesion function.
Hypothesis: The antibody-triggered B-cell aggregation phenotype can depend on CD39-mediated nucleotide turnover, physical adhesive association, or both.
Type: Cell adhesion with nucleotide-metabolism and surface-expression controls
Experiment: Test separately expressed, sequence-verified human products with CDP and UDP alongside ATP/ADP positive controls under matched calcium/magnesium conditions. Quantify CMP/UMP and inorganic phosphate with time courses, enzyme-free and catalytically inactive controls, and verify expression, purification and membrane context. Report each product independently; nucleotide-triphosphate turnover alone does not establish its diphosphate reaction.
Hypothesis: Human CD39 can have distinguishable CDP and UDP hydrolysis rates that are not resolved by the inspected substrate panel.
Type: Product-resolved substrate kinetics
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