Kennedy pathway (CDP-choline / CDP-ethanolamine synthesis of PC and PE)

The Kennedy pathway is the principal de-novo route to the two most abundant membrane glycerophospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE). It runs as two parallel three-step branches that converge on a common diacylglycerol (DAG) acceptor. In the CDP-choline branch, choline kinase (CHKA/CHKB) phosphorylates choline to phosphocholine; the rate-limiting, membrane-regulated CTP:phosphocholine cytidylyltransferase (PCYT1A/PCYT1B) converts phosphocholine + CTP to CDP-choline; and a CDP-alcohol phosphotransferase (CHPT1, or the dual-specificity CEPT1) transfers phosphocholine from CDP-choline onto DAG to make PC + CMP. In the parallel CDP-ethanolamine branch, ethanolamine kinase (ETNK1/ETNK2) makes phosphoethanolamine, the rate-controlling CTP:phosphoethanolamine cytidylyltransferase (PCYT2) makes CDP-ethanolamine, and the ethanolaminephosphotransferases (the selenoprotein SELENOI/EPT1, or CEPT1) transfer phosphoethanolamine onto DAG to make PE + CMP. The two branches are linked by phosphatidylethanolamine N-methyltransferase (PEMT), an ER enzyme (liver-enriched) that performs three sequential SAM-dependent methylations of PE to PC — the only way to make PC without preformed choline, and a major consumer of methyl groups. The amphitropic cytidylyltransferase PCYT1A senses membrane PC content, making it the key regulatory node. Inherited defects span a striking phenotypic range: PCYT1A congenital lipodystrophy / spondylometaphyseal dysplasia with cone-rod dystrophy, CHKB megaconial congenital muscular dystrophy, and PCYT2 and SELENOI hereditary spastic paraplegia. The same three-step branches operate in fungi, where the kinases are cytosolic, the cytidylyltransferases associate with the nuclear/ER membrane, and the two CDP-alcohol phosphotransferases overlap in specificity (the yeast ethanolaminephosphotransferase also uses CDP-choline, and fission yeast has a single dual-specificity enzyme). In fungi the Kennedy pathway runs in parallel with the CDP-diacylglycerol pathway, which makes PE by phosphatidylserine decarboxylation and PC by PE methylation when ethanolamine and choline are not supplied.

MODULE:kennedy_pathway_phospholipid_synthesisDRAFTCONCRETEMetabolic Pathwaymodules/kennedy_pathway_phospholipid_synthesis.yaml
phosphatidylcholine biosynthetic processGO:0006656 phosphatidylethanolamine biosynthetic processGO:0006646
YeastPathways:PWY3O-450
phosphatidylcholine biosynthesis I (S. cerevisiae, SGD YeastPathways)
CKI1 (CHOLINE-KINASE-RXN), PCT1 (2.7.7.15-RXN) and CPT1 (RXN-5781). All retained; EKI1 (which also has choline kinase activity, PMID:10329685) and EPT1 (which also uses CDP-choline, PMID:1847919) were added as secondary catalysts.
YeastPathways:PWY3O-259
phospholipid biosynthesis II (Kennedy pathway) (S. cerevisiae, SGD YeastPathways)
EKI1 (ETHANOLAMINE-KINASE-RXN), ECT1 (2.7.7.14-RXN) and EPT1 (ETHANOLAMINEPHOSPHOTRANSFERASE-RXN). All retained; CKI1, which also phosphorylates ethanolamine (PMID:10329685), was added.
PMID:22345606
Metabolism and regulation of glycerolipids in the yeast Saccharomyces cerevisiae.
In the yeast Kennedy pathway the cytosolic EKI1 and CKI1 kinases, the nuclear/ER membrane-associated ECT1 and PCT1 cytidylyltransferases and the EPT1 and CPT1 phosphotransferases make PE and PC from ethanolamine and choline, using DAG supplied by PAH1; Ept1 also catalyses the CDP-choline reaction.
PMID:10329685
Isolation and characterization of the Saccharomyces cerevisiae EKI1 gene encoding ethanolamine kinase.
EKI1 encodes ethanolamine kinase (with choline kinase activity); EKI1 and CKI1 account for all ethanolamine and choline kinase activity.
PMID:8982874
Isolation and characterization of ECT1 gene encoding CTP: phosphoethanolamine cytidylyltransferase of Saccharomyces cerevisiae.
ECT1 encodes the catalytic subunit of CTP:phosphoethanolamine cytidylyltransferase.
PMID:2848840
The sn-1,2-diacylglycerol ethanolaminephosphotransferase activity of Saccharomyces cerevisiae. Isolation of mutants and cloning of the EPT1 gene.
ept1 mutants have 30- to 90-fold less ethanolaminephosphotransferase activity; EPT1 overexpression raises both ethanolamine- and cholinephosphotransferase activity.
PMID:1847919
sn-1,2-diacylglycerol choline- and ethanolaminephosphotransferases in Saccharomyces cerevisiae. Mixed micellar analysis of the CPT1 and EPT1 gene products.
CPT1 and EPT1 are the structural genes for DAG choline- and ethanolaminephosphotransferases; Ept1 uses CDP-ethanolamine and CDP-choline, Cpt1 is relatively specific for CDP-choline; the double null is viable.
GO:0006656
phosphatidylcholine biosynthetic process
CHKA/CHKB, PCYT1A/PCYT1B, CHPT1/CEPT1 (and PEMT) carry out PC biosynthesis (GO:0006656).
GO:0006646
phosphatidylethanolamine biosynthetic process
ETNK1/ETNK2, PCYT2, SELENOI/CEPT1 carry out PE biosynthesis (GO:0006646).
file:human/CHKA/CHKA-ai-review.yaml
CHKA gene review (human)
The choline->phosphocholine step (UniProtKB:P35790, GO:0004103) matches the completed human CHKA review.
file:human/CHKB/CHKB-ai-review.yaml
CHKB gene review (human)
The choline->phosphocholine step (UniProtKB:Q9Y259, GO:0004103) matches the completed human CHKB review.
file:human/PCYT1A/PCYT1A-ai-review.yaml
PCYT1A gene review (human)
The rate-limiting phosphocholine->CDP-choline step (UniProtKB:P49585, GO:0004105) matches the completed human PCYT1A review.
file:human/PCYT1B/PCYT1B-ai-review.yaml
PCYT1B gene review (human)
The phosphocholine->CDP-choline step (UniProtKB:Q9Y5K3, GO:0004105) matches the completed human PCYT1B review.
file:human/CHPT1/CHPT1-ai-review.yaml
CHPT1 gene review (human)
The CDP-choline + DAG -> PC step (UniProtKB:Q8WUD6, GO:0004142) matches the completed human CHPT1 review.
file:human/CEPT1/CEPT1-ai-review.yaml
CEPT1 gene review (human)
The dual CDP-choline/CDP-ethanolamine + DAG -> PC/PE step (UniProtKB:Q9Y6K0, GO:0004142/GO:0004307) matches the completed human CEPT1 review.
file:human/ETNK1/ETNK1-ai-review.yaml
ETNK1 gene review (human)
The ethanolamine->phosphoethanolamine step (UniProtKB:Q9HBU6, GO:0004305) matches the completed human ETNK1 review.
file:human/ETNK2/ETNK2-ai-review.yaml
ETNK2 gene review (human)
The ethanolamine->phosphoethanolamine step (UniProtKB:Q9NVF9, GO:0004305) matches the completed human ETNK2 review.
file:human/PCYT2/PCYT2-ai-review.yaml
PCYT2 gene review (human)
The rate-controlling phosphoethanolamine->CDP-ethanolamine step (UniProtKB:Q99447, GO:0004306) matches the completed human PCYT2 review.
file:human/SELENOI/SELENOI-ai-review.yaml
SELENOI gene review (human)
The CDP-ethanolamine + DAG -> PE step (UniProtKB:Q9C0D9, GO:0004307) matches the completed human SELENOI review.
file:human/PEMT/PEMT-ai-review.yaml
PEMT gene review (human)
The PE -> PC methylation crosslink (UniProtKB:Q9UBM1, GO:0004608) matches the completed human PEMT review.
8Nodes
7Parts
0Variant Sets
0Variants
7Annotons
5Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:kennedy_pathway_phospholipid_synthesis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • choline_phosphorylation → phosphocholine_cytidylylation [NOT_CHECKED]
    Non-CoA head-group or phospholipid intermediate; the upstream product is the downstream substrate.
  • phosphocholine_cytidylylation → pc_synthesis [NOT_CHECKED]
    Non-CoA head-group or phospholipid intermediate; the upstream product is the downstream substrate.
  • ethanolamine_phosphorylation → phosphoethanolamine_cytidylylation [NOT_CHECKED]
    Non-CoA head-group or phospholipid intermediate; the upstream product is the downstream substrate.
  • phosphoethanolamine_cytidylylation → pe_synthesis [NOT_CHECKED]
    Non-CoA head-group or phospholipid intermediate; the upstream product is the downstream substrate.
  • pe_synthesis → pe_to_pc_methylation [NOT_CHECKED]
    Non-CoA head-group or phospholipid intermediate; the upstream product is the downstream substrate.

Function consistency and core coverage

24 gene-function check(s) reflected in core functions · 0 conflict(s) · 1 evidence or coverage gap(s) (40 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
chk_activity CHKA (human)
UniProtKB:P35790
Family Representative 		choline kinase activity
GO:0004103 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
chk_activity CHKB (human)
UniProtKB:Q9Y259
Family Representative 		choline kinase activity
GO:0004103 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
chk_activity CKI1 (Saccharomyces cerevisiae)
UniProtKB:P20485
Family Representative 		choline kinase activity
GO:0004103 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
chk_activity EKI1 (Saccharomyces cerevisiae)
UniProtKB:Q03764
Family Representative 		choline kinase activity
GO:0004103 		Non Core Supported
The review explicitly retains this function as non-core; promotion into core_functions is not implied.
chk_activity eki1 / SPAC13G7.12c (Schizosaccharomyces pombe)
UniProtKB:Q10276
Family Representative 		choline kinase activity
GO:0004103 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pcyt1_activity PCYT1A (human)
UniProtKB:P49585
Family Representative 		choline-phosphate cytidylyltransferase activity
GO:0004105 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pcyt1_activity PCYT1B (human)
UniProtKB:Q9Y5K3
Family Representative 		choline-phosphate cytidylyltransferase activity
GO:0004105 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pcyt1_activity PCT1 / CCT1 (Saccharomyces cerevisiae)
UniProtKB:P13259
Family Representative 		choline-phosphate cytidylyltransferase activity
GO:0004105 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pcyt1_activity pcy1 / SPCC1827.02c (Schizosaccharomyces pombe)
UniProtKB:O74975
Family Representative 		choline-phosphate cytidylyltransferase activity
GO:0004105 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
chpt_activity CHPT1 (human)
UniProtKB:Q8WUD6
Family Representative 		diacylglycerol cholinephosphotransferase activity
GO:0004142 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
chpt_activity CEPT1 (human, dual)
UniProtKB:Q9Y6K0
Family Representative 		diacylglycerol cholinephosphotransferase activity
GO:0004142 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
chpt_activity CPT1 (Saccharomyces cerevisiae)
UniProtKB:P17898
Family Representative 		diacylglycerol cholinephosphotransferase activity
GO:0004142 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
chpt_activity EPT1 (Saccharomyces cerevisiae, dual)
UniProtKB:P22140
Family Representative 		diacylglycerol cholinephosphotransferase activity
GO:0004142 		Non Core Supported
The review explicitly retains this function as non-core; promotion into core_functions is not implied.
chpt_activity ept1 / SPAC22A12.10 (Schizosaccharomyces pombe, dual)
UniProtKB:O13901
Family Representative 		diacylglycerol cholinephosphotransferase activity
GO:0004142 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
etnk_activity ETNK1 (human)
UniProtKB:Q9HBU6
Family Representative 		ethanolamine kinase activity
GO:0004305 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
etnk_activity ETNK2 (human)
UniProtKB:Q9NVF9
Family Representative 		ethanolamine kinase activity
GO:0004305 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
etnk_activity EKI1 (Saccharomyces cerevisiae)
UniProtKB:Q03764
Family Representative 		ethanolamine kinase activity
GO:0004305 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
etnk_activity CKI1 (Saccharomyces cerevisiae)
UniProtKB:P20485
Family Representative 		ethanolamine kinase activity
GO:0004305 		Non Core Supported
The review explicitly retains this function as non-core; promotion into core_functions is not implied.
etnk_activity eki1 / SPAC13G7.12c (Schizosaccharomyces pombe)
UniProtKB:Q10276
Family Representative 		ethanolamine kinase activity
GO:0004305 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pcyt2_activity PCYT2 (human)
UniProtKB:Q99447
Family Representative 		ethanolamine-phosphate cytidylyltransferase activity
GO:0004306 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pcyt2_activity ECT1 / MUQ1 (Saccharomyces cerevisiae)
UniProtKB:P33412
Family Representative 		ethanolamine-phosphate cytidylyltransferase activity
GO:0004306 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pcyt2_activity ect1 / SPAC15E1.05c (Schizosaccharomyces pombe)
UniProtKB:Q9UTI6
Family Representative 		ethanolamine-phosphate cytidylyltransferase activity
GO:0004306 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ept_activity SELENOI / EPT1 (human)
UniProtKB:Q9C0D9
Family Representative 		ethanolaminephosphotransferase activity
GO:0004307 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ept_activity CEPT1 (human, dual)
UniProtKB:Q9Y6K0
Family Representative 		ethanolaminephosphotransferase activity
GO:0004307 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ept_activity EPT1 (Saccharomyces cerevisiae, dual)
UniProtKB:P22140
Family Representative 		ethanolaminephosphotransferase activity
GO:0004307 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ept_activity ept1 / SPAC22A12.10 (Schizosaccharomyces pombe, dual)
UniProtKB:O13901
Family Representative 		ethanolaminephosphotransferase activity
GO:0004307 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pemt_activity PEMT (human)
UniProtKB:Q9UBM1
Family Representative 		phosphatidylethanolamine N-methyltransferase activity
GO:0004608 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
chk_activity choline/ethanolamine kinase family
PANTHER:PTHR22603:SF93
Family 		choline kinase activity
GO:0004103 		Family Supported
Family review supports GO:0004103 for PANTHER:PTHR22603:SF93. Choline kinase subfamilies and fungal SF93, as kennedy_pathway_phospholipid_synthesis asserts on the base family; the ETNK subfamilies are ethanolamine-specific.
chk_activity choline/ethanolamine kinase family
PANTHER:PTHR22603:SF36
Family 		choline kinase activity
GO:0004103 		Family Supported
Family review supports GO:0004103 for PANTHER:PTHR22603:SF36. Choline kinase subfamilies and fungal SF93, as kennedy_pathway_phospholipid_synthesis asserts on the base family; the ETNK subfamilies are ethanolamine-specific.
chk_activity choline/ethanolamine kinase family
PANTHER:PTHR22603:SF35
Family 		choline kinase activity
GO:0004103 		Family Supported
Family review supports GO:0004103 for PANTHER:PTHR22603:SF35. Choline kinase subfamilies and fungal SF93, as kennedy_pathway_phospholipid_synthesis asserts on the base family; the ETNK subfamilies are ethanolamine-specific.
chk_activity choline/ethanolamine kinase family
PANTHER:PTHR22603:SF25
Family 		choline kinase activity
GO:0004103 		Family Supported
Family review supports GO:0004103 for PANTHER:PTHR22603:SF25. Choline kinase subfamilies and fungal SF93, as kennedy_pathway_phospholipid_synthesis asserts on the base family; the ETNK subfamilies are ethanolamine-specific.
chk_activity choline/ethanolamine kinase family
PANTHER:PTHR22603:SF26
Family 		choline kinase activity
GO:0004103 		Family Supported
Family review supports GO:0004103 for PANTHER:PTHR22603:SF26. Choline kinase subfamilies and fungal SF93, as kennedy_pathway_phospholipid_synthesis asserts on the base family; the ETNK subfamilies are ethanolamine-specific.
pcyt1_activity PCYT1 / choline-phosphate cytidylyltransferase family
PANTHER:PTHR10739
Family 		choline-phosphate cytidylyltransferase activity
GO:0004105 		Family Supported
Family review supports GO:0004105 FAMILY_WIDE. Asserted by kennedy_pathway_phospholipid_synthesis; accepted by PCT1, the S. pombe CCT and PCYT1A/B.
chpt_activity CDP-alcohol phosphotransferase (CHPT1/CEPT1) family
PANTHER:PTHR10414:SF32
Family 		diacylglycerol cholinephosphotransferase activity
GO:0004142 		Family Supported
Family review supports GO:0004142 for PANTHER:PTHR10414:SF32. Choline phosphotransferases and dual choline/ethanolamine phosphotransferases (CHPT1 in SF32, CEPT1 in SF27, S. cerevisiae CPT1 and S. pombe SPAC22A12.10 in SF37), as kennedy_pathway_phospholipid_synthesis selects. Not the ethanolamine-specific SELENOI/EPT1 subfamily (SF47). S. cerevisiae EPT1 (SF37) keeps it as a minor activity.
chpt_activity CDP-alcohol phosphotransferase (CHPT1/CEPT1) family
PANTHER:PTHR10414:SF27
Family 		diacylglycerol cholinephosphotransferase activity
GO:0004142 		Family Supported
Family review supports GO:0004142 for PANTHER:PTHR10414:SF27. Choline phosphotransferases and dual choline/ethanolamine phosphotransferases (CHPT1 in SF32, CEPT1 in SF27, S. cerevisiae CPT1 and S. pombe SPAC22A12.10 in SF37), as kennedy_pathway_phospholipid_synthesis selects. Not the ethanolamine-specific SELENOI/EPT1 subfamily (SF47). S. cerevisiae EPT1 (SF37) keeps it as a minor activity.
chpt_activity CDP-alcohol phosphotransferase (CHPT1/CEPT1) family
PANTHER:PTHR10414:SF37
Family 		diacylglycerol cholinephosphotransferase activity
GO:0004142 		Family Supported
Family review supports GO:0004142 for PANTHER:PTHR10414:SF37. Choline phosphotransferases and dual choline/ethanolamine phosphotransferases (CHPT1 in SF32, CEPT1 in SF27, S. cerevisiae CPT1 and S. pombe SPAC22A12.10 in SF37), as kennedy_pathway_phospholipid_synthesis selects. Not the ethanolamine-specific SELENOI/EPT1 subfamily (SF47). S. cerevisiae EPT1 (SF37) keeps it as a minor activity.
etnk_activity choline/ethanolamine kinase family (ETNK)
PANTHER:PTHR22603
Family 		ethanolamine kinase activity
GO:0004305 		Family Supported
Family review supports GO:0004305 FAMILY_WIDE. Ethanolamine kinase activity is shared by all subfamilies, including the CHKs and CKI1 at lower efficiency; accepted or kept by every reviewed member.
pcyt2_activity PCYT2 / ethanolamine-phosphate cytidylyltransferase family
PANTHER:PTHR45780
Family 		ethanolamine-phosphate cytidylyltransferase activity
GO:0004306 		Family Supported
Family review supports GO:0004306 FAMILY_WIDE. Asserted by kennedy_pathway_phospholipid_synthesis; accepted by PCYT2, ECT1 and SPAC15E1.05c.
ept_activity CDP-alcohol phosphotransferase (SELENOI/CEPT1) family
PANTHER:PTHR10414
Family 		ethanolaminephosphotransferase activity
GO:0004307 		Family Function Unreviewed
Family review leaves GO:0004307 UNRESOLVED. The family spans phosphobase-transfer enzymes with different donor specificity, including CHPT1, SELENOI/EPT1 and dual-specificity CEPT1 branches. Human CEPT1 catalyzes phosphatidylcholine and phosphatidylethanolamine synthesis using CDP-choline or CDP-ethanolamine and diacylglycerol; mixed-micelle assays also resolve acceptor-lipid preferences (PMID:12216837). Thus phosphatidylethanolamine synthesis is supported for characterized ethanolamine-accepting branches, but not for every choline-preferring relative. The fly CG33116 assignment alone does not establish donor specificity or a ceramide rather than diacylglycerol acceptor.
pemt_activity PEMT / phospholipid N-methyltransferase family
PANTHER:PTHR15458
Family 		phosphatidylethanolamine N-methyltransferase activity
GO:0004608 		Family Supported
Family review supports GO:0004608 FAMILY_WIDE. The module uses this MF for the animal PEMT variant. The first methylation, PE to PMME, is the main physiological role of PEMT. In fungi CHO2 (PTHR32138) does it, and OPI3 keeps only a low-rate first-step activity. The capacity is therefore shared by the family, but its weight differs between lineages. Do not read this term on a fungal member as meaning that OPI3 replaces CHO2. No PAINT node asserts it.

Gene-review completeness (21/21 grounded genes reviewed)

21 complete review(s) · 6 with deep research · 0 missing review · 15 reviewed but lacking deep research

Gene Review Complete Deep research
CEPT1 Q9Y6K0 ✓ ✓ ✗
CHKA P35790 ✓ ✓ ✗
CHKB Q9Y259 ✓ ✓ ✗
CHPT1 Q8WUD6 ✓ ✓ ✗
CKI1 P20485 ✓ ✓ ✓
CPT1 P17898 ✓ ✓ ✓
ECT1 P33412 ✓ ✓ ✓
EKI1 Q03764 ✓ ✓ ✓
EPT1 P22140 ✓ ✓ ✓
ETNK1 Q9HBU6 ✓ ✓ ✗
ETNK2 Q9NVF9 ✓ ✓ ✗
PCT1 P13259 ✓ ✓ ✓
PCYT1A P49585 ✓ ✓ ✗
PCYT1B Q9Y5K3 ✓ ✓ ✗
PCYT2 Q99447 ✓ ✓ ✗
PEMT Q9UBM1 ✓ ✓ ✗
SELENOI Q9C0D9 ✓ ✓ ✗
SPAC13G7.12c Q10276 ✓ ✓ ✗
SPAC15E1.05c Q9UTI6 ✓ ✓ ✗
SPAC22A12.10 O13901 ✓ ✓ ✗
SPCC1827.02c O74975 ✓ ✓ ✗

Details

Context
EukaryotaNCBITaxon:2759
cytosolGO:0005829 endoplasmic reticulum membraneGO:0005789 nucleusGO:0005634
Kennedy pathway (PC / PE synthesis)Metabolic Pathwaykennedy_pathway_phospholipid_synthesis
phosphatidylcholine biosynthetic processGO:0006656 phosphatidylethanolamine biosynthetic processGO:0006646
Context
EukaryotaNCBITaxon:2759
cytosolGO:0005829 endoplasmic reticulum membraneGO:0005789 nucleusGO:0005634

GENERALIZE (YeastPathways project, 2026-10): the human-grounded module was extended to fungi without changing its human leaves. Each step gained S. cerevisiae and S. pombe exemplars in the existing PANTHER families (CKI1/EKI1 and S. pombe eki1 in PTHR22603; PCT1 and pcy1 in PTHR10739; ECT1 and ect1 in PTHR45780; CPT1/EPT1 and ept1 in PTHR10414), and the two YeastPathways models and the PomBase phospholipid model were linked. Fungal specificities overlap: CKI1 and EKI1 each phosphorylate both choline and ethanolamine and together account for all kinase activity (PMID:10329685), so both are listed for both kinase steps; EPT1 uses CDP-choline as well as CDP-ethanolamine (PMID:1847919, PMID:2848840) and is listed on both phosphotransferase steps; S. pombe has a single kinase (SPAC13G7.12c) and a single CDP-alcohol phosphotransferase (SPAC22A12.10). Fungal PCT1 and ECT1 associate with the nuclear/ER membrane rather than being soluble (PMID:22345606); the annoton locations remain those of the human enzymes. The PE methylation crosslink is kept as the animal PEMT step; the fungal CHO2/OPI3 route is in cdp_dag_phospholipid_synthesis. YeastCyc corrections: EKI1 (choline kinase) and EPT1 (cholinephosphotransferase) are missing from PWY3O-450, and CKI1 (ethanolamine kinase) from PWY3O-259. GO-CAM disagreements: both YeastPathways models place all activities in cytosol, including the membrane-bound CPT1 and EPT1; PWY3O-259 uses the broad process GO:0046474 rather than GO:0006646. The ethanolamine-phosphate supply from sphingoid-base phosphate lyase (DPL1) and choline/ethanolamine import (HNM1) are upstream context. Previous curation notes follow. Kennedy pathway de-novo glycerophospholipid synthesis (GO:0006656 PC + GO:0006646 PE), grounded to eleven completed human gene reviews. CDP-CHOLINE branch -> PC: CHKA (P35790) + CHKB (Q9Y259) share PTHR22603, GO:0004103 (also ethanolamine kinase GO:0004305) -> PCYT1A (P49585) + PCYT1B (Q9Y5K3) share PTHR10739, GO:0004105 (rate-limiting, amphitropic; PCYT1A membrane-PC-sensing, shuttles nucleus<->ER) -> CHPT1 (Q8WUD6) + CEPT1 (Q9Y6K0) share PTHR10414, GO:0004142. CDP-ETHANOLAMINE branch -> PE: ETNK1 (Q9HBU6) + ETNK2 (Q9NVF9) share PTHR22603, GO:0004305 -> PCYT2 (Q99447 PTHR45780, GO:0004306, rate-controlling) -> SELENOI/EPT1 (Q9C0D9, a selenoprotein, + ether-PE) + CEPT1 share PTHR10414, GO:0004307. CROSSLINK: PEMT (Q9UBM1 PTHR15458, GO:0004608) methylates PE->PC 3x with SAM (only choline-independent PC route; NAFLD). CEPT1 is dual-specificity (appears in both phosphotransferase nodes). All 11 kinases/transferases require Mg2+/Mn2+; the DAG acceptor and CMP byproduct link to glycerolipid metabolism. GO term ids/labels verified against the local go.db. Disorders: PCYT1A lipodystrophy / SMD-CRD; CHKB megaconial muscular dystrophy; PCYT2 and SELENOI hereditary spastic paraplegia.

Connections

The phosphocholine made by CHKA/CHKB is the substrate for PCYT1A/PCYT1B.
The CDP-choline made by PCYT1 is the phosphocholine donor for CHPT1/CEPT1.
The phosphoethanolamine made by ETNK1/ETNK2 is the substrate for PCYT2.
The CDP-ethanolamine made by PCYT2 is the phosphoethanolamine donor for SELENOI/CEPT1.
The PE made by the CDP-ethanolamine branch is the substrate PEMT methylates to PC.
Part 1: choline phosphorylation
Choline kinase (CHKA/CHKB)Reactioncholine_phosphorylation

Annotons

CHKA/CHKB: choline kinase
chk_activity
Participant: Family: choline/ethanolamine kinase family
Family:
choline/ethanolamine kinase family
Representative Members: CHKA (human)UniProtKB:P35790 CHKB (human)UniProtKB:Q9Y259 CKI1 (Saccharomyces cerevisiae)UniProtKB:P20485 EKI1 (Saccharomyces cerevisiae)UniProtKB:Q03764 eki1 / SPAC13G7.12c (Schizosaccharomyces pombe)UniProtKB:Q10276

Function

choline kinase activityGO:0004103
Substrates: choline ATP (Mg2+)
Products: phosphocholine ADP

Locations

cytosolGO:0005829

Phosphorylate choline to phosphocholine (also ethanolamine kinase activity).

Part 2: CDP-choline formation (rate-limiting)
CTP:phosphocholine cytidylyltransferase (PCYT1A/PCYT1B)Reactionphosphocholine_cytidylylation

Annotons

PCYT1A/PCYT1B: choline-phosphate cytidylyltransferase
pcyt1_activity
Participant: Family: PCYT1 / choline-phosphate cytidylyltransferase family
Family:
PCYT1 / choline-phosphate cytidylyltransferase familyPANTHER:PTHR10739
Representative Members: PCYT1A (human)UniProtKB:P49585 PCYT1B (human)UniProtKB:Q9Y5K3 PCT1 / CCT1 (Saccharomyces cerevisiae)UniProtKB:P13259 pcy1 / SPCC1827.02c (Schizosaccharomyces pombe)UniProtKB:O74975

Function

choline-phosphate cytidylyltransferase activityGO:0004105
Substrates: phosphocholine CTP
Products: CDP-choline diphosphate

Locations

nucleusGO:0005634

Convert phosphocholine + CTP to CDP-choline (rate-limiting, membrane-regulated).

Part 3: phosphatidylcholine synthesis (DAG acceptor)
Cholinephosphotransferase (CHPT1/CEPT1)Reactionpc_synthesis

Annotons

CHPT1/CEPT1: diacylglycerol cholinephosphotransferase
chpt_activity
Participant: Family: CDP-alcohol phosphotransferase (CHPT1/CEPT1) family
Family:
CDP-alcohol phosphotransferase (CHPT1/CEPT1) family
Representative Members: CHPT1 (human)UniProtKB:Q8WUD6 CEPT1 (human, dual)UniProtKB:Q9Y6K0 CPT1 (Saccharomyces cerevisiae)UniProtKB:P17898 EPT1 (Saccharomyces cerevisiae, dual)UniProtKB:P22140 ept1 / SPAC22A12.10 (Schizosaccharomyces pombe, dual)UniProtKB:O13901

Function

diacylglycerol cholinephosphotransferase activityGO:0004142
Substrates: CDP-choline 1,2-diacylglycerol (Mg2+/Mn2+)
Products: phosphatidylcholine (PC) CMP

Locations

endoplasmic reticulum membraneGO:0005789

Transfer phosphocholine from CDP-choline to DAG, forming PC.

Part 4: ethanolamine phosphorylation
Ethanolamine kinase (ETNK1/ETNK2)Reactionethanolamine_phosphorylation

Annotons

ETNK1/ETNK2: ethanolamine kinase
etnk_activity
Participant: Family: choline/ethanolamine kinase family (ETNK)
Family:
choline/ethanolamine kinase family (ETNK)PANTHER:PTHR22603
Representative Members: ETNK1 (human)UniProtKB:Q9HBU6 ETNK2 (human)UniProtKB:Q9NVF9 EKI1 (Saccharomyces cerevisiae)UniProtKB:Q03764 CKI1 (Saccharomyces cerevisiae)UniProtKB:P20485 eki1 / SPAC13G7.12c (Schizosaccharomyces pombe)UniProtKB:Q10276

Function

ethanolamine kinase activityGO:0004305
Substrates: ethanolamine ATP (Mg2+)
Products: phosphoethanolamine ADP

Locations

cytosolGO:0005829

Phosphorylate ethanolamine to phosphoethanolamine.

Part 5: CDP-ethanolamine formation (rate-controlling)
CTP:phosphoethanolamine cytidylyltransferase (PCYT2)Reactionphosphoethanolamine_cytidylylation

Annotons

PCYT2: ethanolamine-phosphate cytidylyltransferase
pcyt2_activity
Participant: Family: PCYT2 / ethanolamine-phosphate cytidylyltransferase family
Family:
PCYT2 / ethanolamine-phosphate cytidylyltransferase familyPANTHER:PTHR45780
Representative Members: PCYT2 (human)UniProtKB:Q99447 ECT1 / MUQ1 (Saccharomyces cerevisiae)UniProtKB:P33412 ect1 / SPAC15E1.05c (Schizosaccharomyces pombe)UniProtKB:Q9UTI6

Function

ethanolamine-phosphate cytidylyltransferase activityGO:0004306
Substrates: phosphoethanolamine CTP
Products: CDP-ethanolamine diphosphate

Locations

cytosolGO:0005829

Convert phosphoethanolamine + CTP to CDP-ethanolamine (rate-controlling).

Part 6: phosphatidylethanolamine synthesis (DAG acceptor)
Ethanolaminephosphotransferase (SELENOI/CEPT1)Reactionpe_synthesis

Annotons

SELENOI/CEPT1: ethanolaminephosphotransferase
ept_activity
Participant: Family: CDP-alcohol phosphotransferase (SELENOI/CEPT1) family
Family:
CDP-alcohol phosphotransferase (SELENOI/CEPT1) familyPANTHER:PTHR10414
Representative Members: SELENOI / EPT1 (human)UniProtKB:Q9C0D9 CEPT1 (human, dual)UniProtKB:Q9Y6K0 EPT1 (Saccharomyces cerevisiae, dual)UniProtKB:P22140 ept1 / SPAC22A12.10 (Schizosaccharomyces pombe, dual)UniProtKB:O13901

Function

ethanolaminephosphotransferase activityGO:0004307
Substrates: CDP-ethanolamine 1,2-diacylglycerol (Mg2+/Mn2+)
Products: phosphatidylethanolamine (PE) CMP

Locations

endoplasmic reticulum membraneGO:0005789

Transfer phosphoethanolamine from CDP-ethanolamine to DAG, forming PE.

Part 7: PE -> PC methylation crosslink

Animal single-enzyme PEMT. In fungi the same conversion is split between CHO2 (first methylation) and the PEMT-family OPI3 (second and third); that two-enzyme variant is modelled in cdp_dag_phospholipid_synthesis, where PE methylation completes the CDP-DAG route to PC.

Phosphatidylethanolamine N-methyltransferase (PEMT)Reactionpe_to_pc_methylation

Annotons

PEMT: phosphatidylethanolamine N-methyltransferase
pemt_activity
Participant: Family: PEMT / phospholipid N-methyltransferase family
Family:
PEMT / phospholipid N-methyltransferase familyPANTHER:PTHR15458
Representative Members: PEMT (human)UniProtKB:Q9UBM1

Function

phosphatidylethanolamine N-methyltransferase activityGO:0004608
Substrates: phosphatidylethanolamine (PE) S-adenosyl-L-methionine (3x)
Products: phosphatidylcholine (PC) S-adenosyl-L-homocysteine (3x)

Locations

endoplasmic reticulum membraneGO:0005789

Methylate PE (3x SAM) to PC (choline-independent route).