NTE1 (Neuropathy Target Esterase homolog) is an intracellular phospholipase B that catalyzes the double deacylation of phosphatidylcholine (PC) to glycerophosphocholine. This lysophospholipase enzyme plays a critical role in membrane lipid homeostasis and phospholipid turnover, particularly in response to environmental conditions like inositol availability, temperature stress, and choline presence. NTE1 activity functionally interacts with the phosphatidylinositol/phosphatidylcholine transfer protein Sec14p and influences transcriptional regulation of phospholipid biosynthetic genes through its impact on the OPI1 repressor.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004622 phosphatidylcholine lysophospholipase A1 activity | IBA GO_REF:0000033 | ACCEPT | Summary: NTE1 hydrolyzes 1-acyl-sn-glycero-3-phosphocholine (lysoPC) to glycerophosphocholine and a fatty acid (EC 3.1.1.5), the lysophospholipase step of PC deacylation; microsomal lysoPC activity is half-maximal at ~0.05 mM. Reason: NTE1 lies in the NTE-family PAINT node PANTHER:PTN000369206 that inherited phosphatidylcholine lysophospholipase activity, with NTE1's own IDA evidence corroborating this ancestral placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000369206 Β· PTN000369206 SUPPORTS TRANSFER This NTE-family PAINT node correctly propagates phosphatidylcholine lysophospholipase activity to yeast Nte1; NTE1 itself contributes descendant experimental support for the same activity. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 PMID:15044461 YML059c, a Saccharomyces cerevisiae protein with sequence homology to NTE, had similar catalytic properties to the mammalian enzyme in assays of microsome preparations file:yeast/NTE1/NTE1-deep-research-falcon.md NTE1/YML059C encodes a **patatin-like serine esterase/phospholipase** |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: GFP-tagged NTE1 shows a reticular ER pattern and immunogold EM places it on ER tubules; the ER is where NTE1 carries out PC deacylation. Reason: NTE1 falls within the PANTHER:PTN000369206 NTE-family node that propagates ER localization, matching the direct ER-localization evidence for yeast Nte1. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000369206 Β· PTN000369206 SUPPORTS TRANSFER This NTE-family PAINT node correctly propagates ER localization to yeast Nte1, whose own direct evidence places the enzyme at the ER. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 PMID:15044461 like NTE, was localized to the endoplasmic reticulum. |
| GO:0004622 phosphatidylcholine lysophospholipase A1 activity | IEA GO_REF:0000120 | ACCEPT | Summary: NTE1 hydrolyzes 1-acyl-sn-glycero-3-phosphocholine (lysoPC) to glycerophosphocholine and a fatty acid (EC 3.1.1.5), the lysophospholipase step of PC deacylation; microsomal lysoPC activity is half-maximal at ~0.05 mM. Reason: Direct experimental (IDA) lysophospholipase activity on lyso-PC; core catalytic MF. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: NTE1 is a multi-pass ER membrane protein (two N-terminal TM helices, large cytoplasmic catalytic region), embedding the lipase at the ER bilayer where its PC substrate resides. Reason: Precise membrane sub-localization consistent with its multi-pass topology; core CC term. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 |
| GO:0005811 lipid droplet | IEA GO_REF:0000044 | REMOVE | Summary: NTE1 reproducibly co-purified with the lipid-droplet fraction, but the follow-up GFP microscopy in the same study did not support lipid-droplet localization. Reason: PMID:24868093 reported Nte1 in the high-confidence lipid-droplet proteomic cluster, then found that Nte1-GFP did not colocalize with lipid droplets and interpreted Nte1 as a co-purifying protein rather than a bona fide lipid-droplet protein. Supporting Evidence: PMID:24868093 three (Ecm29, Nte1, and Taz1) did not show LD localization when we examined C-terminal GFP fusions of them by microscopy, suggesting that they purify with the LD fraction, but do not localize to this organelle. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: This root-level lipid-metabolism term is uninformative for NTE1, whose defined role is phosphatidylcholine deacylation within phospholipid metabolism; the specific PC terms should carry the annotation. Reason: Very broad parent; superseded by specific phosphatidylcholine process terms. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 |
| GO:0016042 lipid catabolic process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: NTE1's catabolic activity is specifically the breakdown of phosphatidylcholine to GPC and fatty acids; the generic 'lipid catabolic process' adds no specificity beyond the dedicated PC catabolic term. Reason: Over-general catabolic parent; the specific PC catabolic process term applies. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: NTE1 is a serine hydrolase, but the bare 'hydrolase activity' parent is uninformative; the specific lysophospholipase/PC-deacylating activity is the experimentally defined function and should be used instead. Reason: Over-general parent; NTE1 already carries specific lysophospholipase and phospholipase B activity annotations that capture its catalytic function. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 |
| GO:0046470 phosphatidylcholine metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: By deacylating PC to GPC, NTE1 is central to PC metabolism and turnover, feeding the PC deacylation/reacylation (remodeling) pathway that maintains PC species composition. Reason: Core PC-metabolism process directly tied to the enzyme's reaction. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 |
| GO:0046486 glycerolipid metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: NTE1 metabolizes the glycerophospholipid PC, but 'glycerolipid metabolic process' is an over-broad parent; the specific phosphatidylcholine metabolic/catabolic terms convey its actual role. Reason: Over-general parent superseded by the specific PC metabolic terms already annotated. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 |
| GO:0102545 B-type glycerophospholipase activity | IEA GO_REF:0000116 | ACCEPT | Summary: NTE1 is a phospholipase B that fully deacylates phosphatidylcholine, removing both sn-1 and sn-2 acyl chains to yield glycerophosphocholine and two free fatty acids; this B-type activity is its defining catalytic function. Reason: Captures the experimentally established double-deacylation (phospholipase B) chemistry; a core MF term. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: GFP-tagged NTE1 shows a reticular ER pattern and immunogold EM places it on ER tubules; the ER is where NTE1 carries out PC deacylation. Supported by HDA, IBA, and direct (IDA) evidence. Reason: Well-supported primary localization where the enzyme acts; core CC term. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 |
| GO:0005783 endoplasmic reticulum | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: GFP-tagged NTE1 shows a reticular ER pattern and immunogold EM places it on ER tubules; the ER is where NTE1 carries out PC deacylation. Supported by HDA, IBA, and direct (IDA) evidence. Reason: Well-supported primary localization where the enzyme acts; core CC term. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 |
| GO:0004622 phosphatidylcholine lysophospholipase A1 activity | IDA PMID:15044461 Neuropathy target esterase and its yeast homologue degrade p... | ACCEPT | Summary: NTE1 hydrolyzes 1-acyl-sn-glycero-3-phosphocholine (lysoPC) to glycerophosphocholine and a fatty acid (EC 3.1.1.5), the lysophospholipase step of PC deacylation; microsomal lysoPC activity is half-maximal at ~0.05 mM. Reason: Direct experimental (IDA) lysophospholipase activity on lyso-PC; core catalytic MF. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 |
| GO:0005783 endoplasmic reticulum | IDA PMID:15044461 Neuropathy target esterase and its yeast homologue degrade p... | ACCEPT | Summary: GFP-tagged NTE1 shows a reticular ER pattern and immunogold EM places it on ER tubules; the ER is where NTE1 carries out PC deacylation. Supported by HDA, IBA, and direct (IDA) evidence. Reason: Well-supported primary localization where the enzyme acts; core CC term. Supporting Evidence: UniProt:Q04958 RecName: Full=Lysophospholipase NTE1; EC=3.1.1.5 |
| GO:0034638 phosphatidylcholine catabolic process | IMP PMID:15044461 Neuropathy target esterase and its yeast homologue degrade p... | ACCEPT | Summary: NTE1 is the major route of intracellular PC catabolism: nte1Ξ cells fail to produce GPC from PC and show markedly slowed PC turnover (~60% label retained vs ~20% in WT after 90 min). Reason: Experimental (IMP) core process directly demonstrated by the deletion phenotype. Supporting Evidence: PMID:15044461 Yeast lacking YML059c were viable under all conditions examined but, unlike the wild-type strain, did not convert PtdCho to GroPCho. |
| GO:0071071 regulation of phospholipid biosynthetic process | IMP PMID:19841481 NTE1-encoded phosphatidylcholine phospholipase b regulates t... | KEEP AS NON CORE | Summary: NTE1-driven PC deacylation modulates the OPI1 repressor and thereby transcription of phospholipid biosynthetic genes; this transcriptional/regulatory effect is a downstream consequence of its catalytic role. Reason: Indirect regulatory effect via OPI1, secondary to the enzyme's catalytic core function. Supporting Evidence: PMID:19841481 We show here that the activity of NTE1-encoded phospholipase B (Nte1p) prevents the attenuation of transcription of genes encoding enzymes involved in phospholipid synthesis in response to increased rates of PC synthesis by affecting the nuclear localization of the transcriptional repressor Opi1p. |
| GO:0004620 glycerophospholipase activity | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: NTE1's specific accepted molecular functions capture its phosphatidylcholine lysophospholipase and B-type glycerophospholipase activities; generic glycerophospholipase adds no precision. Reason: This broad ARBA-inferred molecular-function parent is covered by the experimentally supported PC lysophospholipase/B-type phospholipase activities. Supporting Evidence: PMID:15044461 YML059c, a Saccharomyces cerevisiae protein with sequence homology to NTE, had similar catalytic properties to the mammalian enzyme in assays of microsome preparations |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:15044461 Neuropathy target esterase and its yeast homologue degrade p... | ACCEPT | Summary: NTE1 is a multi-pass ER membrane protein; ER localization was experimentally shown in the Nte1 catalytic paper. Reason: This duplicate direct UniProt row is consistent with the accepted ER and UniProt-SubCell ER-membrane rows. The experiment placed GFP-tagged YML059c/Nte1 at the ER, and UniProt topology resolves the ER-associated protein to the membrane. Supporting Evidence: PMID:15044461 like NTE, was localized to the endoplasmic reticulum. |
| GO:0005811 lipid droplet | EXP PMID:24868093 High confidence proteomic analysis of yeast LDs identifies a... | REMOVE | Summary: NTE1 reproducibly co-purified with the lipid-droplet fraction, but the follow-up GFP microscopy in the same study did not support lipid-droplet localization. Reason: The paper cited for this row explicitly distinguished Nte1 from bona fide LD proteins: the C-terminal GFP fusion did not localize to lipid droplets, suggesting that Nte1 co-purifies with the LD fraction without being located there. Supporting Evidence: PMID:24868093 three (Ecm29, Nte1, and Taz1) did not show LD localization when we examined C-terminal GFP fusions of them by microscopy, suggesting that they purify with the LD fraction, but do not localize to this organelle. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: This root-level lipid-metabolism term is uninformative for NTE1, whose defined role is phosphatidylcholine deacylation within phospholipid metabolism. Reason: This InterPro2GO row duplicates a broad parent already marked as over-annotated; the specific phosphatidylcholine catabolic and metabolic process rows capture the real biological process. Supporting Evidence: PMID:15044461 Yeast lacking YML059c were viable under all conditions examined but, unlike the wild-type strain, did not convert PtdCho to GroPCho. |
| GO:0016020 membrane | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Generic membrane localization is true but less precise than the accepted ER-membrane annotation. Reason: NTE1 is specifically an endoplasmic-reticulum membrane lipase; adding the root membrane term from ARBA loses the important compartmental specificity. Supporting Evidence: PMID:15044461 like NTE, was localized to the endoplasmic reticulum. |
| GO:0052689 carboxylic ester hydrolase activity | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: NTE1 is a serine ester hydrolase, but this parent term is less precise than its accepted phosphatidylcholine lysophospholipase and B-type glycerophospholipase activities. Reason: The ARBA molecular-function row is an over-broad hydrolase parent; NTE1 already carries experimentally supported, substrate-specific phospholipase terms. Supporting Evidence: PMID:15044461 YML059c, a Saccharomyces cerevisiae protein with sequence homology to NTE, had similar catalytic properties to the mammalian enzyme in assays of microsome preparations |
| GO:0102545 B-type glycerophospholipase activity | EXP PMID:15044461 Neuropathy target esterase and its yeast homologue degrade p... | ACCEPT | Summary: NTE1 catalyzes complete deacylation of phosphatidylcholine to glycerophosphocholine and free fatty acids; this EXP row directly supports the same core phospholipase B activity as the RHEA row. Reason: PMID:15044461 is the primary Nte1/YML059c experiment establishing the phospholipase B reaction against phosphatidylcholine in yeast. Supporting Evidence: PMID:15044461 Yeast lacking YML059c were viable under all conditions examined but, unlike the wild-type strain, did not convert PtdCho to GroPCho. |
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Download this section (compressed HTML)Q: How does NTE1 regulate phospholipid homeostasis in the endoplasmic reticulum and what determines its substrate specificity?
Q: What role does NTE1 play in membrane remodeling and how does its activity affect ER morphology and function?
Q: How is NTE1 expression and activity regulated in response to lipid stress and membrane composition changes?
Q: What are the relationships between NTE1 and other phospholipid metabolic enzymes in maintaining cellular lipid balance?
Experiment: Lipidomics analysis of NTE1 knockout strains to characterize changes in phospholipid composition and membrane properties
Experiment: Electron microscopy analysis of ER morphology in NTE1-deficient cells to assess its role in membrane organization
Experiment: Enzyme kinetics studies to characterize NTE1 substrate specificity and regulatory mechanisms
Experiment: Subcellular fractionation and mass spectrometry to study NTE1 localization and protein interactions in different membrane compartments
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Download this section (compressed HTML)Serine esterase; homolog of human neuropathy target esterase (NTE); Nte1p-mediated phosphatidylcholine turnover influences transcription factor Opi1p localization, affecting transcriptional regulation of phospholipid biosynthesis genes
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