Ectonucleotide pyrophosphatase/phosphodiesterase family member 7 (ENPP7) is an alkaline sphingomyelin phosphodiesterase (EC 3.1.4.12) that hydrolyzes sphingomyelin to ceramide and phosphocholine. Unlike other ENPP family members that degrade nucleotides, ENPP7 evolved specificity for phospholipid substrates: structural analysis (PDB 5TCD) shows the catalytic site is solvent-exposed with no nucleotide-binding slot, and the choline headgroup is stabilized by a cation-pi box formed by tyrosines Tyr109, Tyr166, and Tyr194. Expressed primarily in intestinal epithelium and human liver/bile, the enzyme requires specific bile salts (taurocholate, taurochenodeoxycholate) for activity, and a nearby hydrophobic loop (342-351) with surface cation patches likely mediates interaction with bile salt micelles. ENPP7 is a single-pass type I membrane protein anchored to the plasma membrane via a C-terminal hydrophobic domain with the catalytic domain extending extracellularly; pancreatic trypsin can cleave it from the mucosa, releasing a soluble active form into the intestinal lumen. The enzyme functions in dietary sphingomyelin digestion, generates anti-proliferative ceramide, inactivates pro-inflammatory platelet-activating factor (PAF), and regulates cholesterol absorption. Reduced ENPP7 activity is associated with colorectal cancer, cholangiocarcinoma, and inflammatory bowel disease. Circulating plasma ENPP7 has been identified as a biomarker associated with faster glycaemic deterioration in type 2 diabetes (Slieker et al. 2023).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0008081 phosphoric diester hydrolase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phosphoric diester hydrolase activity based on phylogenetic inference. ENPP7 hydrolyzes the phosphodiester bond in sphingomyelin between ceramide and phosphocholine. Reason: This correctly describes ENPP7's core enzymatic activity. The enzyme catalyzes hydrolysis of the phosphodiester bond in sphingomyelin. While sphingomyelin phosphodiesterase activity (GO:0004767) is more specific, this parent term is appropriate. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md The primary enzymatic function of ENPP7 is the hydrolysis of sphingomyelin, a major dietary and membrane phospholipid, cleaving the phosphodiester bond between the ceramide backbone and the choline headgroup to generate two products: ceramide and free phosphocholine file:human/ENPP7/ENPP7-deep-research-perplexity-lite.md See deep research file for comprehensive analysis |
| GO:0004767 sphingomyelin phosphodiesterase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Sphingomyelin phosphodiesterase activity - the primary molecular function of ENPP7 (EC 3.1.4.12). Reason: This is the core molecular function of ENPP7. The enzyme is also known as alkaline sphingomyelinase and specifically hydrolyzes sphingomyelin to ceramide and phosphocholine. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md ENPP7, also designated as ectonucleotide pyrophosphatase/phosphodiesterase family member 7 and commonly known as alkaline sphingomyelin phosphodiesterase (alk-SMase) or intestinal alkaline sphingomyelinase |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma membrane localization - ENPP7 is anchored to the cell membrane via C-terminal hydrophobic domain. Reason: ENPP7 is a membrane-anchored ecto-enzyme with its catalytic domain extending extracellularly. The C-terminal hydrophobic signal anchor domain embeds it within cell membranes. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md The protein is synthesized with an N-terminal signal peptide important for transport to the endoplasmic reticulum and a C-terminal hydrophobic signal anchor domain that embeds it within cell membranes |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000043 | ACCEPT | Summary: Lipid metabolic process - ENPP7 functions in sphingolipid metabolism by hydrolyzing sphingomyelin. Reason: Accurate parent term. ENPP7 is the key enzyme for dietary sphingomyelin digestion and generates ceramide, a bioactive lipid. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md ENPP7 occupies a critical position as the entry point for dietary sphingomyelin into the major ceramide-generating pathway of the intestinal epithelium |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Hydrolase activity - general enzyme class for ENPP7. Reason: Correct parent term. ENPP7 is a hydrolase that cleaves phosphodiester bonds in sphingomyelin and other substrates. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md The primary enzymatic function of ENPP7 is the hydrolysis of sphingomyelin |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | MODIFY | Summary: Metal ion binding - ENPP7 contains a dizinc catalytic center essential for activity. Reason: While correct, the more specific term GO:0008270 (zinc ion binding) is more appropriate since ENPP7 specifically requires zinc ions (not general metal ions) for catalysis. Proposed replacements: zinc ion binding Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md The catalytic mechanism of ENPP7 depends on a conserved dizinc center nearly identical in arrangement to other members of the ENPP family |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding from large-scale interactome study. Reason: Per curation guidelines, generic "protein binding" is uninformative and should be avoided. This high-throughput study does not provide mechanistic insight into ENPP7's function as a sphingomyelin phosphodiesterase. The enzyme's function is best captured by its enzymatic activity rather than non-specific protein interactions. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0046479 glycosphingolipid catabolic process | TAS Reactome:R-HSA-9840310 | MARK AS OVER ANNOTATED | Summary: Glycosphingolipid catabolic process from Reactome pathway annotation. Sphingomyelin is NOT a glycosphingolipid (it has a phosphocholine headgroup, not a carbohydrate), so this term is a mis-classification of ENPP7's actual reaction. The Reactome source pathway R-HSA-9840310 describes lysosomal ganglioside catabolism, not intestinal sphingomyelin hydrolysis. A more accurate process term is GO:0006684 (sphingomyelin metabolic process). Reason: Sphingomyelin (an ENPP7 substrate) is a phosphosphingolipid, not a glycosphingolipid. ENPP7 acts on phosphodiester bonds of sphingomyelin and lyso-PC; it does not act on glycosphingolipids. Use GO:0006684 sphingomyelin metabolic process instead. Proposed replacements: sphingomyelin metabolic process Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md Sphingomyelin arriving in the intestinal lumen undergoes initial hydrolysis by ENPP7 to generate ceramide and phosphocholine; this ceramide subsequently enters further catabolic pathways through the actions of neutral ceramidase and ceramidase-like enzymes |
| GO:0004767 sphingomyelin phosphodiesterase activity | TAS Reactome:R-HSA-1640164 | ACCEPT | Summary: Sphingomyelin phosphodiesterase activity from Reactome pathway - ENPP7 hydrolyzes sphingomyelin. Reason: Core molecular function. ENPP7 is an alkaline sphingomyelinase that hydrolyzes sphingomyelin to ceramide and phosphocholine. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md ENPP7, also designated as ectonucleotide pyrophosphatase/phosphodiesterase family member 7 and commonly known as alkaline sphingomyelin phosphodiesterase (alk-SMase) or intestinal alkaline sphingomyelinase |
| GO:0004767 sphingomyelin phosphodiesterase activity | IDA PMID:16255717 Intestinal alkaline sphingomyelinase hydrolyses and inactiva... | ACCEPT | Summary: Direct assay demonstrating sphingomyelin phosphodiesterase activity and PAF inactivation. Reason: PMID:16255717 demonstrated that ENPP7 has phospholipase C activity toward PAF and lysophosphatidylcholine in addition to sphingomyelin, providing experimental evidence for the enzyme's catalytic activities. Supporting Evidence: PMID:16255717 Alkaline sphingomyelinase (alk-SMase) is a new member of the NPP (nucleotide pyrophosphatase/phosphodiesterase) family that hydrolyses SM (sphingomyelin) to generate ceramide in the intestinal tract file:human/ENPP7/ENPP7-deep-research-perplexity.md ENPP7 acts as an inactivator of platelet-activating factor (PAF), a potent pro-inflammatory phosphodiester-linked lipid synthesized during immune responses and inflammation file:human/ENPP7/ENPP7-deep-research-falcon.md Beyond sphingomyelin, ENPP7 is reported to function as a **lyso-phospholipase C (lyso-PLC)** and to hydrolyze **Lysophosphatidylcholine (LPC/lyso-PC)** and **platelet-activating factor (PAF)** to yield phosphocholine-containing products PMID:34958798 ENPP7, also known as alkaline sphingomyelinase (Alk-SMase), hydrolyzes SM to ceramide and phosphocholine. Additionally, it can function as a lyso-PLC that hydrolyzes LPC and PAF to generate phosphocholine, similar to ENNP6, and the artificial substrate para-nitrophenylphosphorylcholine (pNPPC) |
| GO:0008081 phosphoric diester hydrolase activity | IDA PMID:16255717 Intestinal alkaline sphingomyelinase hydrolyses and inactiva... | ACCEPT | Summary: Direct assay showing phosphodiesterase activity toward sphingomyelin and PAF. Reason: PMID:16255717 experimentally demonstrated that ENPP7 hydrolyzes phosphodiester bonds in both sphingomyelin and platelet-activating factor. Supporting Evidence: PMID:16255717 alkSMase cleaved the phosphocholine head group from PAF and generated 1-O-alkyl-2-acetyl-sn-glycerol file:human/ENPP7/ENPP7-deep-research-perplexity.md The primary enzymatic function of ENPP7 is the hydrolysis of sphingomyelin, a major dietary and membrane phospholipid, cleaving the phosphodiester bond between the ceramide backbone and the choline headgroup |
| GO:0044241 lipid digestion | ISS GO_REF:0000024 | ACCEPT | Summary: Lipid digestion - ENPP7 is the primary enzyme for dietary sphingomyelin digestion in the intestine. Reason: Knockout mouse studies definitively established ENPP7's essential role in sphingomyelin digestion. ENPP7-deficient mice showed 6-fold accumulation of undigested sphingomyelin and 95% reduction in fatty acid absorption from sphingomyelin. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md Knockout studies in mice definitively established this role: ENPP7-deficient mice displayed a dramatic six-fold accumulation of undigested radiolabeled sphingomyelin in intestinal contents one hour after gavage feeding |
| GO:0045797 positive regulation of intestinal cholesterol absorption | ISS GO_REF:0000024 | MODIFY | Summary: ENPP7 indirectly affects cholesterol absorption through sphingomyelin depletion. Reason: The relationship is complex - sphingomyelin inhibits cholesterol absorption, and ENPP7-mediated depletion of sphingomyelin could enhance cholesterol bioavailability. However, the ceramide generated also inhibits cholesterol absorption. The net effect may be negative regulation rather than positive. This annotation may be inaccurate. Proposed replacements: regulation of intestinal cholesterol absorption Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md Dietary supplementation with sphingomyelin inhibits cholesterol absorption in the gastrointestinal tract... When ENPP7 hydrolyzes sphingomyelin to ceramide, the depletion of sphingomyelin in mixed micelles and the simultaneous generation of ceramide further enhances the inhibition of cholesterol absorption |
| GO:0055089 fatty acid homeostasis | ISS GO_REF:0000024 | ACCEPT | Summary: Fatty acid homeostasis - ENPP7 enables absorption of fatty acids from sphingomyelin. Reason: ENPP7-mediated sphingomyelin digestion is required for absorption of the fatty acid component. Knockout mice showed 95% reduction in fatty acid absorption from sphingomyelin. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md absorption of the fatty acid component of sphingomyelin was reduced by 95 percent in knockout mice compared to wild-type controls, demonstrating that sphingomyelin digestion is not merely a secondary function but is mechanistically coupled to lipid absorption |
| GO:1904729 regulation of intestinal lipid absorption | ISS GO_REF:0000024 | ACCEPT | Summary: Regulation of intestinal lipid absorption through sphingomyelin digestion. Reason: ENPP7 is essential for intestinal absorption of sphingolipid-derived fatty acids and regulates cholesterol absorption through sphingomyelin/ceramide balance. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md ENPP7 indirectly modulates cholesterol absorption through its regulation of sphingomyelin levels in the intestinal lumen, reflecting a sophisticated lipid-lipid interaction mechanism |
| GO:2000304 positive regulation of ceramide biosynthetic process | ISS GO_REF:0000024 | MODIFY | Summary: Positive regulation of ceramide biosynthesis - ENPP7 generates ceramide by hydrolyzing sphingomyelin. Reason: ENPP7 does not regulate ceramide biosynthesis - it directly produces ceramide by hydrolyzing sphingomyelin. This is a catabolic reaction, not regulation of biosynthesis. A more accurate term would be related to ceramide generation from sphingomyelin catabolism. Proposed replacements: ceramide metabolic process Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md The primary enzymatic function of ENPP7 is the hydrolysis of sphingomyelin, a major dietary and membrane phospholipid, cleaving the phosphodiester bond between the ceramide backbone and the choline headgroup to generate two products: ceramide and free phosphocholine |
| GO:2000755 positive regulation of sphingomyelin catabolic process | ISS GO_REF:0000024 | MODIFY | Summary: Positive regulation of sphingomyelin catabolic process. Reason: ENPP7 does not regulate sphingomyelin catabolism - it directly catalyzes sphingomyelin catabolism. The enzyme IS the sphingomyelin catabolic process in the intestine. A more accurate annotation would be the catabolic process itself. Proposed replacements: sphingomyelin metabolic process Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md The primary enzymatic function of ENPP7 is the hydrolysis of sphingomyelin |
| GO:0004767 sphingomyelin phosphodiesterase activity | IDA PMID:28292932 Crystal structure of the human alkaline sphingomyelinase pro... | ACCEPT | Summary: Crystal structure study (PDB 5TCD, 5UDY) revealing sphingomyelin phosphodiesterase mechanism and substrate specificity. Reason: PMID:28292932 determined the crystal structure of human ENPP7, revealing the aromatic box (Tyr109, Tyr166, Tyr194) that specifically recognizes the choline headgroup of sphingomyelin through cation-Ο interactions. Supporting Evidence: PMID:28292932 alk-SMase recognizes the choline moiety of its substrates via an NPP7-specific aromatic box composed of tyrosine residues file:human/ENPP7/ENPP7-deep-research-perplexity.md The crystal structure of human ENPP7 in complex with phosphocholine, determined in 2017 and deposited as PDB structures 5TCD and 5UDY, revealed the molecular basis for ENPP7's remarkable substrate specificity for sphingomyelin within the NPP family file:human/ENPP7/ENPP7-deep-research-falcon.md The choline moiety is stabilized by a "cationβΟ box" composed of Tyr109, Tyr166, and Tyr194, providing a structural rationale for preference toward choline-containing substrates. PMID:34958798 The ENPP7 catalytic site is more solvent-exposed compared with ENPP6 (Fig. 2). Moreover, there is no nucleotide-binding slot, and the choline moiety is surrounded and stabilized by tyrosines (Tyr109, Tyr166, and Tyr194), referred to as the cation-Ο box |
| GO:0005886 plasma membrane | IDA PMID:15205117 Pancreatic trypsin cleaves intestinal alkaline sphingomyelin... | ACCEPT | Summary: Plasma membrane localization demonstrated - ENPP7 can be cleaved by pancreatic trypsin and released from membrane. Reason: PMID:15205117 showed that ENPP7 is anchored to the plasma membrane and can be cleaved by pancreatic trypsin at a site just above the membrane anchor, releasing an active form into the intestinal lumen. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md pancreatic trypsin can proteolytically cleave ENPP7 at a tryptic recognition site positioned just above the membrane-embedded hydrophobic anchor, generating a form with higher specific activity that circulates freely in the intestinal lumen PMID:15205117 Pancreatic trypsin cleaves intestinal alkaline sphingomyelinase from mucosa and enhances the sphingomyelinase activity. PMID:34958798 ENPP4, ENPP5, and ENPP7 are single-pass type I membrane proteins file:human/ENPP7/ENPP7-deep-research-falcon.md ENPP7 is a **single-pass type I membrane protein** adapted as a phospholipase rather than a nucleotide-hydrolyzing ENPP. |
| GO:0006684 sphingomyelin metabolic process | IDA PMID:28292932 Crystal structure of the human alkaline sphingomyelinase pro... | ACCEPT | Summary: Sphingomyelin metabolic process demonstrated through structural and biochemical characterization. Reason: The crystal structure study confirmed ENPP7's role in sphingomyelin metabolism by revealing the structural basis for substrate recognition and catalysis. Supporting Evidence: PMID:28292932 Absorption of dietary sphingomyelin (SM) requires its initial degradation into ceramide, a process catalyzed by the intestinal enzyme alkaline sphingomyelinase (alk-SMase, NPP7, ENPP7) file:human/ENPP7/ENPP7-deep-research-perplexity.md ENPP7 occupies a critical position as the entry point for dietary sphingomyelin into the major ceramide-generating pathway of the intestinal epithelium |
| GO:0008270 zinc ion binding | IDA PMID:28292932 Crystal structure of the human alkaline sphingomyelinase pro... | ACCEPT | Summary: Crystal structure reveals dizinc catalytic center essential for ENPP7 activity. Reason: PMID:28292932 determined the crystal structure showing the dizinc center coordinated by seven amino acid residues (His353, His203, Asp199 for Zn1; His247, Asp246, Asp39, Thr75 for Zn2). Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md Within the catalytic site depression lies a carefully orchestrated arrangement of two zinc ions, designated Zn1 and Zn2, coordinated by seven amino acid residues from the protein backbone PMID:28292932 2017 Mar 14. Crystal structure of the human alkaline sphingomyelinase provides insights into substrate recognition. file:human/ENPP7/ENPP7-deep-research-falcon.md ENPP7 uses the ENPP/alkaline phosphatase superfamily catalytic architecture with **two ZnΒ²βΊ ions** in the active site. PMID:34958798 The catalytic site is characterized by two zinc ions essential for catalysis and located in a shallow groove, where the substrate binds. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1640164 | ACCEPT | Summary: Plasma membrane localization from Reactome pathway for ENPP7 sphingomyelin hydrolysis. Reason: ENPP7 is a membrane-anchored ecto-enzyme localized to the plasma membrane of intestinal epithelial cells. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md ENPP7 is localized specifically to the surface of intestinal epithelial cells lining the microvilli |
| GO:0004767 sphingomyelin phosphodiesterase activity | IDA PMID:12671034 Purification, localization, and expression of human intestin... | ACCEPT | Summary: Purification study demonstrating sphingomyelin phosphodiesterase activity in human intestine. Reason: PMID:12671034 reported purification, localization, and expression of human intestinal alkaline sphingomyelinase, providing direct experimental evidence for this activity. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md The enzyme was originally discovered in 1969 by Nilsson as a sphingomyelinase activity in intestinal tissue operating at alkaline pH PMID:12671034 2003 Apr 1. Purification, localization, and expression of human intestinal alkaline sphingomyelinase. |
| GO:0004767 sphingomyelin phosphodiesterase activity | IDA PMID:12885774 Identification of human intestinal alkaline sphingomyelinase... | ACCEPT | Summary: Identification of ENPP7 as an alkaline sphingomyelinase with the novel finding of relationship to NPP family. Reason: PMID:12885774 identified human intestinal alkaline sphingomyelinase as a member of the nucleotide phosphodiesterase family, providing key molecular characterization. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md it was not until molecular cloning studies decades later that its evolutionary relationship to the broader NPP family was revealed PMID:12885774 2003 Jul 28. Identification of human intestinal alkaline sphingomyelinase as a novel ecto-enzyme related to the nucleotide phosphodiesterase family. |
| GO:0005794 Golgi apparatus | IDA PMID:12671034 Purification, localization, and expression of human intestin... | ACCEPT | Summary: Golgi apparatus localization during protein processing and transit to plasma membrane. Reason: ENPP7 is a secretory protein that transits through the Golgi apparatus during biosynthesis before reaching the plasma membrane. PMID:12671034 localization studies detected ENPP7 in Golgi compartments. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md The protein is synthesized with an N-terminal signal peptide important for transport to the endoplasmic reticulum PMID:12671034 2003 Apr 1. Purification, localization, and expression of human intestinal alkaline sphingomyelinase. |
| GO:0005902 microvillus | IDA PMID:12671034 Purification, localization, and expression of human intestin... | ACCEPT | Summary: Microvillus localization - ENPP7 is localized to intestinal microvilli where it functions in sphingomyelin digestion. Reason: PMID:12671034 demonstrated that ENPP7 localizes specifically to the microvilli of intestinal epithelial cells, consistent with its role as a digestive enzyme at the brush border. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md ENPP7 is localized specifically to the surface of intestinal epithelial cells lining the microvilli, with particular abundance in the middle jejunum PMID:12671034 2003 Apr 1. Purification, localization, and expression of human intestinal alkaline sphingomyelinase. PMID:37137910 ENPP7 (Ectonucleotide pyrophosphatase/phosphodiesterase-7) is strongly expressed in the small intestine where it is involved in sphingomyelin hydrolysis and the absorption of ceramide and phosphocholine |
| GO:0006684 sphingomyelin metabolic process | IDA PMID:12671034 Purification, localization, and expression of human intestin... | ACCEPT | Summary: Sphingomyelin metabolic process - ENPP7 is the key enzyme for intestinal sphingomyelin metabolism. Reason: PMID:12671034 demonstrated ENPP7's role in sphingomyelin metabolism in the intestine. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md ENPP7 occupies a critical position as the entry point for dietary sphingomyelin into the major ceramide-generating pathway PMID:12671034 2003 Apr 1. Purification, localization, and expression of human intestinal alkaline sphingomyelinase. PMID:37137910 ENPP7 (Ectonucleotide pyrophosphatase/phosphodiesterase-7) is strongly expressed in the small intestine where it is involved in sphingomyelin hydrolysis and the absorption of ceramide and phosphocholine |
| GO:0006684 sphingomyelin metabolic process | IDA PMID:12885774 Identification of human intestinal alkaline sphingomyelinase... | ACCEPT | Summary: Sphingomyelin metabolic process characterized through molecular identification of ENPP7. Reason: PMID:12885774 provided key molecular characterization establishing ENPP7's role in sphingomyelin metabolism. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md The primary enzymatic function of ENPP7 is the hydrolysis of sphingomyelin PMID:12885774 2003 Jul 28. Identification of human intestinal alkaline sphingomyelinase as a novel ecto-enzyme related to the nucleotide phosphodiesterase family. |
| GO:0008156 negative regulation of DNA replication | IDA PMID:12671034 Purification, localization, and expression of human intestin... | KEEP AS NON CORE | Summary: Negative regulation of DNA replication - ceramide generated by ENPP7 has anti-proliferative effects. Reason: This is an indirect effect mediated through ceramide, a bioactive lipid produced by ENPP7 that inhibits cell proliferation. Not a direct function of ENPP7 itself but a downstream consequence of ceramide generation. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md Ceramide operates through multiple molecular mechanisms to suppress cancer cell survival: it activates pro-apoptotic signaling cascades, inhibits anti-apoptotic serine/threonine kinases including AKT, disrupts cell cycle progression PMID:12671034 2003 Apr 1. Purification, localization, and expression of human intestinal alkaline sphingomyelinase. |
| GO:0008285 negative regulation of cell population proliferation | IDA PMID:12671034 Purification, localization, and expression of human intestin... | KEEP AS NON CORE | Summary: Negative regulation of cell proliferation through ceramide generation. Reason: This is an indirect, downstream effect of ENPP7 activity. The ceramide product of sphingomyelin hydrolysis is a well-characterized anti-proliferative lipid. Reduced ENPP7 activity is associated with colorectal cancer, consistent with loss of ceramide-mediated growth suppression. Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md The primary therapeutic interest in ENPP7 derives from its capacity to generate ceramide, a well-characterized bioactive lipid that inhibits cell proliferation and promotes apoptotic cell death across diverse cell types PMID:12671034 2003 Apr 1. Purification, localization, and expression of human intestinal alkaline sphingomyelinase. |
| GO:0016020 membrane | NAS PMID:12885774 Identification of human intestinal alkaline sphingomyelinase... | MODIFY | Summary: General membrane localization - overly broad term. Reason: This is an overly general term. ENPP7 specifically localizes to plasma membrane and microvillus membrane of intestinal epithelial cells. More specific terms (GO:0005886 plasma membrane, GO:0005902 microvillus) are already annotated. Proposed replacements: plasma membrane Supporting Evidence: file:human/ENPP7/ENPP7-deep-research-perplexity.md ENPP7 is localized specifically to the surface of intestinal epithelial cells lining the microvilli PMID:12885774 2003 Jul 28. Identification of human intestinal alkaline sphingomyelinase as a novel ecto-enzyme related to the nucleotide phosphodiesterase family. |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)