CEPT1 (choline/ethanolamine phosphotransferase 1) is a dual-specificity, polytopic integral membrane enzyme of the CDP-alcohol phosphatidyltransferase class-I family that catalyzes the final, committed step of both the CDP-choline and CDP-ethanolamine (Kennedy) branches of glycerophospholipid biosynthesis. It transfers a phosphobase group from a CDP-linked donor to the sn-3 hydroxyl of 1,2-diacyl-sn-glycerol (DAG): using CDP-choline it produces phosphatidylcholine plus CMP (diacylglycerol cholinephosphotransferase activity, EC 2.7.8.2), and using CDP-ethanolamine it produces phosphatidylethanolamine plus CMP (ethanolaminephosphotransferase activity, EC 2.7.8.1). Catalysis requires a divalent metal cofactor, preferring Mg2+ (Mn2+ supports roughly half-maximal activity), coordinated by a conserved di-aspartate CDP-binding motif; the enzyme also has a minor 1-alkenyl/1-alkyl-2-acylglycerol choline phosphotransferase side activity that yields ether (plasmenyl/plasmanyl) choline phospholipids and platelet-activating-factor precursors. CEPT1 is a homodimer with ten transmembrane helices per protomer and a hydrophobic chamber that accommodates the DAG acyl tails during catalysis. It resides in the endoplasmic reticulum membrane and the nuclear (inner) membrane, where channeling of CDP-choline generated by the upstream rate-limiting enzyme CCTalpha drives de novo phosphatidylcholine synthesis. CEPT1 is ubiquitously expressed.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004142 diacylglycerol cholinephosphotransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. CEPT1 transfers phosphocholine from CDP-choline to DAG to make phosphatidylcholine; this phylogenetic inference is fully consistent with direct experimental assays in human/yeast systems. Reason: The IBA is corroborated by direct experimental characterization of the human enzyme (IDA, PMID:10191259, PMID:37137909) and the UniProt catalytic-activity record (EC 2.7.8.2). |
| GO:0004307 ethanolaminephosphotransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. CEPT1 also uses CDP-ethanolamine as phosphobase donor to make phosphatidylethanolamine; this is the second arm of its dual specificity. Reason: Corroborated by direct experimental assay of the human enzyme (IDA, PMID:10191259; TAS PMID:10191259) and the UniProt catalytic-activity record (EC 2.7.8.1). |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Core localization. CEPT1 is an integral ER membrane enzyme; this IBA agrees with the direct human localization study. Reason: Directly supported by immunofluorescence/subcellular fractionation of human CEPT1 (IDA, PMID:12221122) and UniProt subcellular location. |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Golgi localization is a phylogenetic inference (driven in part by fly and mouse orthologs) that is contradicted for the human enzyme. The definitive human study shows CEPT1 is NOT relocalized by brefeldin A (unlike the Golgi-resident paralog CPT1) and localizes to the ER and nuclear membranes, not the Golgi. Reason: Retained (an experimental IBA reflecting ortholog behavior) but marked non-core because direct human evidence places CEPT1 in the ER and nuclear membrane, explicitly excluding the Golgi (PMID:12221122). Supporting Evidence: PMID:12221122 brefeldin A treatment relocalizes CPT1, but not CEPT1, implying CPT1 is found in the Golgi. |
| GO:0006646 phosphatidylethanolamine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Core biological process. CEPT1 catalyzes the last step of the CDP-ethanolamine (Kennedy) branch producing PE. Reason: Consistent with direct experimental annotation of the human enzyme (IDA, PMID:10191259) and the UniProt PE-biosynthesis pathway record. |
| GO:0004142 diacylglycerol cholinephosphotransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (EC/RHEA-based) assertion of the core cholinephosphotransferase activity; redundant with the experimental IDA annotations of the same term but correct. Reason: EC 2.7.8.2 / RHEA mappings correctly capture the experimentally established activity. |
| GO:0004307 ethanolaminephosphotransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (EC/RHEA-based) assertion of the core ethanolaminephosphotransferase activity; redundant with the experimental annotations but correct. Reason: EC 2.7.8.1 / RHEA mappings correctly capture the experimentally established activity. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Over-general and imprecise. CEPT1 is a multi-pass integral membrane protein of the ER and nuclear membrane; a bare cytoplasm assertion (ARBA machine-learning) does not capture its membrane-embedded localization. Reason: The specific ER-membrane / nuclear-membrane localizations supersede this generic term, which mislocalizes an integral membrane enzyme to the soluble cytoplasm. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Correct core localization, derived electronically from the UniProt Subcellular Location vocabulary. Reason: Agrees with direct experimental localization of human CEPT1 (IDA, PMID:12221122). |
| GO:0008654 phospholipid biosynthetic process | IEA GO_REF:0000002 | MODIFY | Summary: Correct but over-general. CEPT1's role is specifically in phosphatidylcholine and phosphatidylethanolamine biosynthesis, which are more informative child terms already annotated experimentally. Reason: Generalizes over the specific PC/PE biosynthetic processes; replace with the specific children that are experimentally supported. Proposed replacements: phosphatidylcholine biosynthetic process phosphatidylethanolamine biosynthetic process |
| GO:0012505 endomembrane system | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Over-general (ARBA machine-learning). CEPT1 has a specific, experimentally determined ER-membrane and nuclear-membrane localization. Reason: The specific ER/nuclear membrane annotations supersede this broad grouping term. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Correct that CEPT1 is membrane-integral, but far too general given the specific ER-membrane / nuclear-membrane annotations. Reason: Uninformative parent of the specific membrane-location annotations already present. |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | IEA GO_REF:0000002 | MODIFY | Summary: Correct but over-general parent term. This is the direct GO parent of the specific diacylglycerol cholinephosphotransferase (GO:0004142) and ethanolaminephosphotransferase (GO:0004307) activities that are experimentally established. Reason: Generalizes over the specific activities; replace with the experimentally supported children. Proposed replacements: diacylglycerol cholinephosphotransferase activity ethanolaminephosphotransferase activity |
| GO:0031965 nuclear membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Correct secondary localization. CEPT1 resides in the nuclear (inner) membrane in addition to the ER, where substrate channeling from nuclear CCTalpha drives de novo PC synthesis. Reason: Electronic assertion (UniProt Subcellular Location) that is directly supported by the human localization study (PMID:12221122). Supporting Evidence: PMID:12221122 confirmed that CPT1 was found in the Golgi and CEPT1 was found in both the endoplasmic reticulum and nuclear membranes. |
| GO:0047359 1-alkenyl-2-acylglycerol choline phosphotransferase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Real but minor side activity. In addition to using diacylglycerol, CEPT1 can transfer phosphocholine to ether-linked (1-O-alkyl / 1-O-alkenyl) 2-acylglycerols, yielding plasmanyl/plasmenyl choline phospholipids and platelet-activating-factor precursors. Reason: Genuine activity (EC 2.7.8.22; characterized in PMID:10893425 and EXP PMID:10191259) but quantitatively minor relative to PC/PE synthesis on diacylglycerol; retained as a non-core function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare protein-binding annotations from a genome-scale binary (Y2H) interactome map (HuRI). Two partners are recorded via IntAct/UniProt: TMEM14B (Q9NUH8) and SPG21 (Q9NZD8). The interactions are not disputed, but the generic GO:0005515 term conveys no specific molecular function and no functional consequence has been established. Reason: Per curation policy, uninformative bare "protein binding" IPI is retained but flagged as over-annotation; no adapter/scaffold function is defined by the high-throughput data. |
| GO:0006646 phosphatidylethanolamine biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: Correct core biological process, derived electronically from the UniPathway PE-synthesis mapping; redundant with the experimental IDA of the same term. Reason: Matches the experimentally established role in PE biosynthesis (PMID:10191259). |
| GO:0006656 phosphatidylcholine biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: Correct core biological process, derived electronically from the UniPathway PC-synthesis mapping; redundant with the experimental IDA of the same term. Reason: Matches the experimentally established role in PC biosynthesis (PMID:10191259, PMID:37137909). |
| GO:0047359 1-alkenyl-2-acylglycerol choline phosphotransferase activity | EXP PMID:10191259 Cloning and expression of a human choline/ethanolaminephosph... | KEEP AS NON CORE | Summary: Experimentally supported minor side activity (ether-lipid / PAF-precursor choline phosphotransferase). CEPT1 displays broad diradylglycerol specificity and can use alkenyl/alkyl-acylglycerol acceptors. Reason: Real activity but minor relative to the core PC/PE synthesis on diacylglycerol; kept as a non-core function. Supporting Evidence: PMID:10191259 In vitro, hCEPT1p displayed broad substrate specificity, utilizing both CDP-choline and CDP-ethanolamine as phosphobase donors to a broad range of diacylglycerols |
| GO:0004142 diacylglycerol cholinephosphotransferase activity | IDA PMID:10191259 Cloning and expression of a human choline/ethanolaminephosph... | ACCEPT | Summary: Core molecular function, directly demonstrated. Recombinant human CEPT1 expressed in a yeast strain lacking endogenous phosphotransferases synthesizes PC from CDP-choline and diacylglycerol in vitro and in vivo. Reason: Direct assay of the human enzyme; the defining catalytic activity of CEPT1. Supporting Evidence: PMID:10191259 Cholinephosphotransferase catalyses the final step in the synthesis of phosphatidylcholine (PtdCho) via the Kennedy pathway by the transfer of phosphocholine from CDP-choline to diacylglycerol. |
| GO:0004142 diacylglycerol cholinephosphotransferase activity | IDA PMID:37137909 Structural basis for catalysis of human choline/ethanolamine... | ACCEPT | Summary: Core molecular function confirmed structurally and biochemically. The cryo-EM study established an in vitro CMP-release assay showing DAG- and Mg2+-dependent PC synthesis from CDP-choline, with the catalytic aspartate D154 essential. Reason: Direct in vitro assay of purified human CEPT1 with structural mechanism. Supporting Evidence: PMID:37137909 Choline/ethanolamine phosphotransferase 1 (CEPT1) catalyzes the last step of the biosynthesis of PC and PE in the Kennedy pathway by transferring the substituted phosphate group from CDP-choline/ethanolamine to diacylglycerol. |
| GO:0004307 ethanolaminephosphotransferase activity | IDA PMID:10191259 Cloning and expression of a human choline/ethanolaminephosph... | ACCEPT | Summary: Core molecular function, directly demonstrated. CEPT1 uses CDP-ethanolamine as phosphobase donor to synthesize PE, the second arm of its dual specificity. Reason: Direct assay of the human enzyme establishing PE synthesis from CDP-ethanolamine. Supporting Evidence: PMID:10191259 Ethanolaminephosphotransferase catalyses an analogous reaction with CDP-ethanolamine as the phosphobase donor for the synthesis of phosphatidylethanolamine (PtdEtn). |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:12221122 The major sites of cellular phospholipid synthesis and molec... | ACCEPT | Summary: Core localization, directly determined. Coimmunofluorescence and subcellular fractionation with ER, Golgi and nuclear markers place CEPT1 in the ER (and nuclear) membrane and specifically exclude the Golgi. Reason: Direct experimental localization of human CEPT1. Supporting Evidence: PMID:12221122 confirmed that CPT1 was found in the Golgi and CEPT1 was found in both the endoplasmic reticulum and nuclear membranes. |
| GO:0006646 phosphatidylethanolamine biosynthetic process | IDA PMID:10191259 Cloning and expression of a human choline/ethanolaminephosph... | ACCEPT | Summary: Core biological process, directly demonstrated. Yeast expressing hCEPT1 incorporate radiolabelled ethanolamine into phospholipids, reconstituting PE synthesis. Reason: Direct assay establishing CEPT1's role in de novo PE biosynthesis. Supporting Evidence: PMID:10191259 efficiently incorporated both radiolabelled choline and ethanolamine into phospholipids |
| GO:0006656 phosphatidylcholine biosynthetic process | IDA PMID:10191259 Cloning and expression of a human choline/ethanolaminephosph... | ACCEPT | Summary: Core biological process, directly demonstrated. Yeast expressing hCEPT1 incorporate radiolabelled choline into phospholipids, reconstituting PC synthesis in vivo. Reason: Direct assay establishing CEPT1's role in de novo PC biosynthesis. Supporting Evidence: PMID:10191259 efficiently incorporated both radiolabelled choline and ethanolamine into phospholipids |
| GO:0006656 phosphatidylcholine biosynthetic process | IDA PMID:37137909 Structural basis for catalysis of human choline/ethanolamine... | ACCEPT | Summary: Core biological process, supported by the structural/biochemical study, which measures DAG-dependent PC production (CMP release) by purified human CEPT1. Reason: Direct in vitro reconstitution of PC synthesis by purified human CEPT1. Supporting Evidence: PMID:37137909 No CMP release was detected in the absence of DAG, confirming that CMP was not produced by the hydrolysis of CDP-choline |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-1482961 | ACCEPT | Summary: Correct core localization. Reactome places the CEPT1-catalyzed conversion of CDP-choline and DAG to PC at the ER membrane. Reason: Consistent with direct experimental ER localization (PMID:12221122). |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-1482962 | ACCEPT | Summary: Correct core localization. Reactome places the CEPT1/EPT1-catalyzed conversion of CDP-ethanolamine and DAG to PE at the ER membrane. Reason: Consistent with direct experimental ER localization (PMID:12221122). |
| GO:0004307 ethanolaminephosphotransferase activity | TAS PMID:10191259 Cloning and expression of a human choline/ethanolaminephosph... | ACCEPT | Summary: Core molecular function (author statement). Independently supported by the direct assay in the same paper demonstrating CDP-ethanolamine-dependent PE synthesis. Reason: Redundant with, and corroborated by, the IDA of the same activity from this paper. Supporting Evidence: PMID:10191259 Ethanolaminephosphotransferase catalyses an analogous reaction with CDP-ethanolamine as the phosphobase donor for the synthesis of phosphatidylethanolamine (PtdEtn). |
| GO:0006629 lipid metabolic process | TAS PMID:10191259 Cloning and expression of a human choline/ethanolaminephosph... | MARK AS OVER ANNOTATED | Summary: Correct but far too general. CEPT1's role is specifically in phosphatidylcholine and phosphatidylethanolamine biosynthesis (already annotated with the specific child terms). Reason: Uninformative high-level parent superseded by the specific PC/PE biosynthetic-process annotations. |
| GO:0016020 membrane | TAS PMID:10191259 Cloning and expression of a human choline/ethanolaminephosph... | MARK AS OVER ANNOTATED | Summary: Correct that CEPT1 is a polytopic membrane protein (the paper notes multiple membrane-spanning domains), but the term is far too general given the specific ER/nuclear membrane annotations. Reason: Uninformative parent of the specific membrane-location annotations already present. |
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