CHPT1 (cholinephosphotransferase 1, EC 2.7.8.2) is a multipass integral membrane enzyme of the Golgi (and endomembrane) system that catalyzes the final, committed step of the CDP-choline (Kennedy) branch of de novo phosphatidylcholine (PC) biosynthesis. It transfers a phosphocholine group from CDP-choline onto the free 3-hydroxyl of 1,2-diacyl-sn-glycerol (DAG), producing phosphatidylcholine and CMP; the reaction requires Mg2+ or Mn2+. CHPT1 belongs to the CDP-alcohol phosphatidyltransferase class-I family and is choline-specific: unlike its paralog CEPT1, which is a dual choline/ethanolamine phosphotransferase, CHPT1 makes PC but not phosphatidylethanolamine. In addition to bulk PC synthesis it can generate platelet-activating factor and its precursor from the corresponding diradylglycerols. Because PC is the most abundant membrane phospholipid, CHPT1 has a central role in the formation and maintenance of cellular and vesicular membranes. It is broadly expressed with strongly tissue-variable levels, being highest in testis, colon, small intestine, heart, prostate and spleen.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004142 diacylglycerol cholinephosphotransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment of the defining choline phosphotransferase activity. This is the core molecular function of CHPT1 and is independently supported by the experimental IDA (PMID:10893425) and by EC 2.7.8.2 / RHEA mapping. Supporting Evidence: file:human/CHPT1/CHPT1-uniprot.txt Catalyzes the final step of de novo phosphatidylcholine (PC) synthesis, i.e. the transfer of choline phosphate from CDP-choline to |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: ER membrane is a phylogenetic (IBA) call for the family. For human CHPT1 specifically, the experimental study that examined localization found CPT1 in the Golgi and its paralog CEPT1 (not CPT1) in the ER and nuclear membranes. ER localization is therefore plausible for the family/paralogs but not directly demonstrated for CHPT1; retained as non-core rather than a core site. Supporting Evidence: PMID:12221122 confirmed that CPT1 was found in the Golgi and CEPT1 was found in both the endoplasmic reticulum and nuclear |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: Golgi localization is well supported: brefeldin A relocalized CPT1 and immunofluorescence/fractionation placed CPT1 in the Golgi (PMID:12221122), and UniProt records Golgi apparatus membrane. Accept; the more precise Golgi membrane term (GO:0000139, IDA) is the core location. Supporting Evidence: PMID:12221122 brefeldin A treatment relocalizes CPT1, but not CEPT1, implying CPT1 is found in the Golgi |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic mapping from the UniProt Golgi apparatus membrane subcellular-location keyword. Consistent with, and superseded by, the experimental IDA to the same term (PMID:12221122). Accept. Supporting Evidence: file:human/CHPT1/CHPT1-uniprot.txt Golgi apparatus membrane |
| GO:0004142 diacylglycerol cholinephosphotransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of the defining activity from EC 2.7.8.2 / RHEA:32939 and ARBA. Redundant with, and confirmed by, the experimental IDA (PMID:10893425). Accept. Supporting Evidence: file:human/CHPT1/CHPT1-uniprot.txt Reaction=CDP-choline + a 1,2-diacyl-sn-glycerol = a 1,2-diacyl-sn- |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | TOO GENERAL | Summary: True but broad: entailed by Golgi apparatus, Golgi membrane and endoplasmic reticulum membrane, kept in this review. Reason: GO's cytoplasm covers everything inside the plasma membrane except the nucleus, organelles and secretory compartments included, so Golgi apparatus, Golgi membrane and endoplasmic reticulum membrane, kept in this review, entail this term and the claim is true. TOO_GENERAL rather than REMOVE. The objection is a reason not to annotate a narrower term such as cytosol, not to remove this one. Summary at removal: An ARBA electronic default that is incorrect for CHPT1. CHPT1 is a multi-pass integral membrane protein of the Golgi (10 TM helices; UniProt), not a soluble cytoplasmic protein. This bulk-cytoplasm call is a clearly-wrong IEA superseded by the experimental Golgi-membrane localization; remove. Supporting Evidence: file:human/CHPT1/CHPT1-uniprot.txt Multi-pass membrane protein |
| GO:0008654 phospholipid biosynthetic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Correct but over-general InterPro2GO parent term. CHPT1's process is precisely phosphatidylcholine biosynthesis / CDP-choline pathway (GO:0006656/GO:0006657, both descendants of this term), which are annotated experimentally. Mark as over-annotated in favor of the specific terms. |
| GO:0012505 endomembrane system | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Very general ARBA location. Consistent with Golgi/ER membrane residence but far less informative than the specific Golgi membrane annotation; over-annotated. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Root-level location from InterPro2GO. True (CHPT1 is a multi-pass membrane protein) but uninformative; superseded by the specific Golgi membrane annotation. |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO parent of the specific activity. GO:0004142 (diacylglycerol cholinephosphotransferase activity) is a subclass of this term and is annotated experimentally (IDA). Over-annotated in favor of the specific MF. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare protein binding from the HuRI systematic binary (Y2H) interactome screen; the partner is TLCD4 (Q96MV1), matching the UniProt INTERACTION record. This IPI is uninformative about molecular function and its biological significance is unclear. Retained (not removed) but marked as over-annotated per curation policy. Supporting Evidence: file:human/CHPT1/CHPT1-uniprot.txt Q8WUD6; Q96MV1: TLCD4; NbExp=3 |
| GO:0006656 phosphatidylcholine biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: Electronic assignment from UniPathway (phosphatidylcholine biosynthesis, step 2/2). This is a core process for CHPT1 and is independently supported by the experimental IDA (PMID:10893425). Accept. Supporting Evidence: file:human/CHPT1/CHPT1-uniprot.txt phosphatidylcholine from phosphocholine: step 2/2. |
| GO:0000139 Golgi membrane | IDA PMID:12221122 The major sites of cellular phospholipid synthesis and molec... | ACCEPT | Summary: Direct experimental localization of CPT1 to the Golgi (brefeldin A relocalization, co-immunofluorescence, subcellular fractionation). This is the core cellular location where CHPT1 acts. Accept. Supporting Evidence: PMID:12221122 confirmed that CPT1 was found in the Golgi and CEPT1 was found in both the endoplasmic reticulum and nuclear |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-1482973 | ACCEPT | Summary: Reactome traceable assertion that the CHPT1 reaction occurs at the Golgi membrane; consistent with the experimental IDA. Accept. Supporting Evidence: Reactome:R-HSA-1482973 At the Golgi membrane, cholinephosphotransferase 1 (CHPT1) converts CDP-choline (CDP-Cho) and diacylglycerol (DAG) to phosphatidylcholine (PC) |
| GO:0004142 diacylglycerol cholinephosphotransferase activity | IDA PMID:10893425 Cloning, genomic organization, and characterization of a hum... | ACCEPT | Summary: Direct experimental demonstration (in vitro enzyme assay plus yeast reconstitution) that hCPT1 is a cholinephosphotransferase-specific enzyme transferring phosphocholine from CDP-choline to DAG to make PC. This is the core, defining molecular function. Accept. Supporting Evidence: PMID:10893425 codes for a cholinephosphotransferase-specific enzyme |
| GO:0006656 phosphatidylcholine biosynthetic process | IDA PMID:10893425 Cloning, genomic organization, and characterization of a hum... | ACCEPT | Summary: Direct experimental evidence that hCPT1 reconstitutes PC synthesis (in yeast devoid of endogenous CPT/EPT activity), establishing its role in phosphatidylcholine biosynthesis. Core process. Accept. Supporting Evidence: PMID:10893425 in vivo measurement of the reconstitution of the phosphatidylcholine and phosphatidylethanolamine biosynthetic pathways in yeast |
| GO:0001558 regulation of cell growth | NAS PMID:10893425 Cloning, genomic organization, and characterization of a hum... | MARK AS OVER ANNOTATED | Summary: In the cited paper the effect on cell growth was specifically a property of the paralog hCEPT1, NOT hCPT1: only hCEPT1-derived activity complemented yeast CPT1 in its SEC14 interaction and affected cell growth. A growth-regulation role is thus not established for CHPT1 by this reference; this NAS is an over-annotation. Supporting Evidence: PMID:10893425 only hCEPT1-derived activity was able to complement the yeast CPT1 gene in its interaction with SEC14 and affect cell growth |
| GO:0006629 lipid metabolic process | TAS PMID:10893425 Cloning, genomic organization, and characterization of a hum... | KEEP AS NON CORE | Summary: Correct but very general parent process. CHPT1's lipid-metabolic role is precisely phosphatidylcholine biosynthesis (annotated experimentally). Retained as a correct broad ancestor but non-core relative to the specific PC-biosynthesis terms. |
| GO:0006657 CDP-choline pathway | NAS PMID:10893425 Cloning, genomic organization, and characterization of a hum... | ACCEPT | Summary: CHPT1 catalyzes the final (second) step of the CDP-choline (Kennedy) pathway. This is the most precise process term for CHPT1 (a subclass of phosphatidylcholine biosynthetic process) and is well supported. Accept as a core process term. Supporting Evidence: file:human/CHPT1/CHPT1-uniprot.txt phosphatidylcholine from phosphocholine: step 2/2. |
| GO:0006663 platelet activating factor biosynthetic process | IDA PMID:10893425 Cloning, genomic organization, and characterization of a hum... | KEEP AS NON CORE | Summary: The study reports that hCPT1 (differing from hCEPT1) can synthesize platelet- activating factor and its precursor from the appropriate diradylglycerols, i.e. its cholinephosphotransferase activity can produce PAF. This is a genuine but secondary activity; the enzyme's core role is bulk PC synthesis. Keep as non-core. Supporting Evidence: PMID:10893425 their capacity to synthesize platelet-activating factor and platelet-activating factor precursor |
| GO:0016020 membrane | NAS PMID:10893425 Cloning, genomic organization, and characterization of a hum... | MARK AS OVER ANNOTATED | Summary: Root-level location. True (CHPT1 is a multi-pass membrane protein) but uninformative and superseded by the specific Golgi membrane annotation; over-annotated. |
| GO:0019992 diacylglycerol binding | NAS PMID:10893425 Cloning, genomic organization, and characterization of a hum... | KEEP AS NON CORE | Summary: DAG is the lipid acceptor substrate of CHPT1, so substrate binding is implied by the transferase mechanism. However, diacylglycerol binding as a standalone signaling/ regulatory MF (as used for C1-domain effectors) is not the appropriate framing here; the informative MF is the cholinephosphotransferase activity. Kept as non-core rather than a core function. |
| GO:0043231 intracellular membrane-bounded organelle | NAS PMID:10893425 Cloning, genomic organization, and characterization of a hum... | MARK AS OVER ANNOTATED | Summary: Very general location term; consistent with Golgi residence but far less informative than the specific Golgi membrane annotation. Over-annotated. |
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