PCYT1A

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004105 choline-phosphate cytidylyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Correct core molecular function; the phylogenetically-inferred cytidylyltransferase activity matches the directly demonstrated human enzyme activity (EC 2.7.7.15). Reason: Core catalytic function of CCTalpha, supported experimentally in human and across the family.
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	ACCEPT	Summary: CCTalpha associates with the ER (and its membrane), where the active membrane-bound form condenses phosphocholine and CTP; consistent with the human IDA localization. Reason: ER is a bona fide site of the active enzyme.
GO:0031210 phosphatidylcholine binding	IBA GO_REF:0000033	ACCEPT	Summary: The amphipathic membrane-binding helix senses PC-deficient membranes; PC binding is the specific readout of this membrane-sensing activity that gates catalysis. Reason: Membrane/phospholipid sensing is intrinsic to CCTalpha regulation.
GO:0003824 catalytic activity	IEA GO_REF:0000002	MODIFY	Summary: Correct but uninformative root-level catalytic term; the specific choline-phosphate cytidylyltransferase activity (GO:0004105) should be used instead. Reason: Generalize/replace with the specific enzymatic activity. Proposed replacements: choline-phosphate cytidylyltransferase activity
GO:0004105 choline-phosphate cytidylyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA duplicate of the core catalytic function (RHEA:18997 / EC 2.7.7.15); correct. Reason: Redundant electronic support for the core MF.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: CCTalpha (distinct from CCTbeta) resides in the nucleus; electronic call is corroborated by the human IDA nuclear localization. Reason: Nuclear localization is a defining feature of the alpha isoform.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: ER membrane is where the active peripheral-membrane form functions; supported by the human IDA/is_active_in annotation from the same locus. Reason: Correct site of the active membrane-bound enzyme.
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: The inactive soluble form of CCTalpha is cytosolic; consistent with the amphitropic interconversion between a soluble and a membrane-bound state. Reason: Cytosol is the reservoir of the inactive soluble pool.
GO:0006657 CDP-choline pathway	IEA GO_REF:0000120	ACCEPT	Summary: CCTalpha performs the committed, rate-limiting step of the CDP-choline (Kennedy) pathway; electronic call matches the human IDA annotation. Reason: Core biological process.
GO:0016020 membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Generic membrane localization from the SubCell "Membrane" mapping; correct but superseded by the more specific ER membrane / nuclear envelope terms. Reason: True but non-specific; specific membrane terms are preferred.
GO:0046470 phosphatidylcholine metabolic process	IEA GO_REF:0000117	MODIFY	Summary: ARBA-derived parent term; the enzyme acts specifically in PC biosynthesis, so the more specific phosphatidylcholine biosynthetic process (GO:0006656) is preferred. Reason: Over-general; replace with the specific biosynthetic process. Proposed replacements: phosphatidylcholine biosynthetic process
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a high-throughput BioPlex 2.0 AP-MS interactome screen; no specific interactor or function is asserted, so it is uninformative. Reason: Uninformative protein-binding IPI from a proteome-scale screen.
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 binary (Y2H) interactome map; no gene-specific biological function is established. Reason: Uninformative protein-binding IPI from a proteome-scale screen.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from the BioPlex 3.0 AP-MS interactome; high-throughput, no specific functional interaction for CCTalpha. Reason: Uninformative protein-binding IPI from a proteome-scale screen.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a multimodal U2OS cell-map (AP-MS + immunofluorescence) screen; no specific interactor-based function is asserted. Reason: Uninformative protein-binding IPI from a proteome-scale screen.
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Captures the CCTalpha self-interaction (P49585-P49585 in IntAct); the enzyme is an obligate homodimer, so self-association is biologically real, though homodimerization activity (GO:0042803) is the more informative term. Reason: Real self-interaction reflecting the homodimeric enzyme; non-core relative to catalysis.
GO:0005516 calmodulin binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-projected from rat P19836 with no primary human evidence; calmodulin binding is not part of the established CCTalpha mechanism and appears to be an over-projection. Reason: Ortholog-projected binding with no supporting human evidence.
GO:0005635 nuclear envelope	IEA GO_REF:0000107	ACCEPT	Summary: Nuclear-envelope localization is a plausible refinement of the nuclear + ER localization of CCTalpha (the enzyme concentrates at the nuclear envelope/reticulum); consistent with the primary human localization data. Reason: Consistent with observed nuclear/ER localization of the alpha isoform.
GO:0006656 phosphatidylcholine biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Correct core process; electronic call matches the human IDA annotation that CCTalpha drives phosphatidylcholine biosynthesis. Reason: Core biological process.
GO:0008289 lipid binding	IEA GO_REF:0000107	ACCEPT	Summary: The amphipathic helix binds membrane lipid to activate the enzyme; lipid binding is a genuine (membrane-sensing) activity, though phosphatidylcholine binding (GO:0031210) is the more specific readout. Reason: Membrane-lipid binding by the amphipathic helix is central to activation.
GO:0031210 phosphatidylcholine binding	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl-projected duplicate of the IBA phosphatidylcholine-binding annotation; the amphipathic helix senses PC-deficient membranes. Reason: Specific membrane-sensing activity; redundant with the IBA call.
GO:0042100 B cell proliferation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Projected from the mouse CCTbeta ortholog (P49586); B-cell proliferation is a CCTbeta-associated phenotype rather than a demonstrated CCTalpha function. Reason: Ortholog (CCTbeta)-transferred process, not shown for CCTalpha.
GO:0042803 protein homodimerization activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: CCTalpha is an obligate homodimer; homodimerization activity correctly captures the self-association required to form the active enzyme. Reason: Real homodimerization underlying the active enzyme; ancillary to catalysis.
GO:0045190 isotype switching	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Projected from the mouse CCTbeta ortholog (P49586); immunoglobulin isotype switching is not an established CCTalpha function. Reason: Ortholog (CCTbeta)-transferred process, not shown for CCTalpha.
GO:0140678 molecular function inhibitor activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Reflects the intramolecular autoinhibitory (AI) helix that constrains the active site in the soluble form; a plausible mechanistic annotation, but it describes an intramolecular regulatory element rather than a standalone effector function. Reason: Captures autoinhibition by the AI helix; regulatory, not a core function.
GO:0004105 choline-phosphate cytidylyltransferase activity	EXP PMID:30559292 Disease-linked mutations in the phosphatidylcholine regulato...	ACCEPT	Summary: Experimentally measured catalytic activity of purified human CCTalpha (and disease variants); direct support for the core molecular function. Reason: Direct experimental evidence for the core catalytic activity.
GO:0016020 membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Generic membrane localization transferred by sequence similarity from rat P19836; correct but superseded by the specific ER membrane / nuclear envelope terms. Reason: True but non-specific membrane association.
GO:0005789 endoplasmic reticulum membrane	IDA PMID:10480912 Distribution of CTP:phosphocholine cytidylyltransferase (CCT...	ACCEPT	Summary: Direct evidence that CCTalpha associates with and is active at the ER membrane (the site of the membrane-bound active enzyme). Reason: Experimentally supported site of the active enzyme.
GO:0042100 B cell proliferation	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Sequence-similarity transfer from the mouse CCTbeta ortholog (P49586); a CCTbeta phenotype, not a demonstrated CCTalpha function. Reason: Ortholog (CCTbeta)-transferred process, not shown for CCTalpha.
GO:0045190 isotype switching	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Sequence-similarity transfer from the mouse CCTbeta ortholog (P49586); not an established function of CCTalpha. Reason: Ortholog (CCTbeta)-transferred process, not shown for CCTalpha.
GO:0004105 choline-phosphate cytidylyltransferase activity	IDA PMID:10480912 Distribution of CTP:phosphocholine cytidylyltransferase (CCT...	ACCEPT	Summary: Direct assay of CCTalpha enzymatic activity; core molecular function. Reason: Direct experimental evidence for the core catalytic activity.
GO:0005634 nucleus	IDA PMID:10480912 Distribution of CTP:phosphocholine cytidylyltransferase (CCT...	ACCEPT	Summary: Direct evidence (isoform-specific antibodies) that CCTalpha, unlike the CCTbeta isoforms, resides in the nucleus in addition to associating with the ER. Reason: Experimentally supported, isoform-defining nuclear localization.
GO:0005783 endoplasmic reticulum	IDA PMID:10480912 Distribution of CTP:phosphocholine cytidylyltransferase (CCT...	ACCEPT	Summary: Direct evidence that CCTalpha associates with the endoplasmic reticulum. Reason: Experimentally supported localization.
GO:0006656 phosphatidylcholine biosynthetic process	IDA PMID:10480912 Distribution of CTP:phosphocholine cytidylyltransferase (CCT...	ACCEPT	Summary: Direct evidence that CCTalpha functions in phosphatidylcholine biosynthesis (its catalytic and complementation activity in the CDP-choline pathway). Reason: Core biological process, experimentally supported.
GO:0006657 CDP-choline pathway	IDA PMID:10480912 Distribution of CTP:phosphocholine cytidylyltransferase (CCT...	ACCEPT	Summary: Direct evidence that CCTalpha acts in the CDP-choline (Kennedy) pathway; it complemented the temperature-sensitive cytidylyltransferase defect in CHO58 cells. Reason: Core biological process, experimentally supported.
GO:0005789 endoplasmic reticulum membrane	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of ER membrane localization from the mouse ortholog (P49586); redundant with the human IDA/IEA ER-membrane annotations. Reason: Correct localization; redundant with primary evidence.
GO:0006656 phosphatidylcholine biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of the PC biosynthesis process from the mouse ortholog (P49586); redundant with the human IDA annotation. Reason: Correct core process; redundant with primary evidence.
GO:0042587 glycogen granule	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Isolated glycogen-granule localization transferred by sequence similarity from the mouse CCTbeta ortholog (P49586); weakly supported and not part of the established CCTalpha localization pattern (nucleus/ER). Reason: Weak, ortholog-projected localization inconsistent with the core CCTalpha sites.
GO:0004105 choline-phosphate cytidylyltransferase activity	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of the catalytic activity from rat P19836; redundant with the human IDA/EXP evidence for the core MF. Reason: Correct core MF; redundant with primary experimental evidence.
GO:0006657 CDP-choline pathway	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of the CDP-choline pathway role from rat P19836; redundant with the human IDA annotation. Reason: Correct core process; redundant with primary evidence.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-1483081	ACCEPT	Summary: Reactome places the active membrane-bound PCYT1 dimer at the ER membrane, where it condenses phosphocholine and CTP to CDP-choline; consistent with the human IDA evidence. Reason: Author-traceable localization consistent with the active enzyme site.
GO:0004105 choline-phosphate cytidylyltransferase activity	TAS PMID:7918629 Primary structure and expression of a human CTP:phosphocholi...	ACCEPT	Summary: The paper cloned the human enzyme and showed lipid-dependent cytidylyltransferase activity of the expressed protein; author statement supports the core MF. Reason: Core catalytic activity, author-supported for the human enzyme.

Gene Description

Existing Annotations Review

Core Functions

CCTalpha catalyzes the rate-limiting, committed step of the CDP-choline (Kennedy) pathway, condensing phosphocholine and CTP to CDP-choline plus diphosphate (EC 2.7.7.15).

References

📚 Additional Documentation

Notes

📄 View Raw YAML