Microsomal fatty-acid elongation cycle (ELOVL or KCS -> KAR -> HACD -> ECR)

Most fatty acids longer than the C16 palmitate made by cytosolic fatty-acid synthase are produced by the microsomal elongation system, a four-reaction cycle on the cytosolic face of the endoplasmic-reticulum membrane that adds two carbons per turn. Each round begins with the rate-limiting, substrate-selective condensation of an acyl-CoA with malonyl-CoA to a 3-oxoacyl-CoA (releasing CO2), catalysed by one of seven fatty-acid elongases (ELOVL1-7) whose chain-length and saturation preferences define which fatty acids a cell makes: ELOVL1/3/6 handle saturated and monounsaturated substrates (ELOVL6 the C16->C18 lipogenic step, ELOVL1 the C22->C26 very-long-chain step for sphingolipids/myelin, ELOVL3 skin/brown-fat lipids), ELOVL2/5 the C20/C22 polyunsaturated fatty acids en route to DHA, ELOVL7 C18-C20 substrates, and ELOVL4 the unique ultra-long-chain (C26-C38) fatty acids of retina, skin and brain. The 3-oxoacyl-CoA is then reduced by the NADPH-dependent 3-ketoacyl-CoA reductase HSD17B12 (KAR) to (3R)-3-hydroxyacyl-CoA, dehydrated by the 3-hydroxyacyl-CoA dehydratases HACD1/HACD2 to (2E)-enoyl-CoA, and reduced by the NADPH-dependent trans-2-enoyl-CoA reductase TECR to the two-carbon-extended saturated acyl-CoA, which re-enters the cycle. The reductase/dehydratase/reductase enzymes are shared across all ELOVLs; substrate specificity resides in the elongase. Inherited defects span the products: ELOVL1 (IKSHD ichthyosis/spastic quadriplegia), ELOVL4 (Stargardt-like macular dystrophy, SCA34, ichthyosis), HACD1 (congenital myopathy), TECR (intellectual disability), reflecting the roles of very-long-chain and ultra-long-chain fatty acids in skin barrier, myelin, retina and muscle. Fungi use ELO-family elongases homologous to the ELOVLs, whose paralogs divide the chain-length range from medium-chain (C12-C14) to C26 substrates, together with orthologous reductase, dehydratase and enoyl reductase; the C26 product is the fatty acid of fungal sphingolipids. Plants run the same four-step cycle but use an unrelated condensing enzyme, the thiolase-fold 3-ketoacyl-CoA synthases (KCS; e.g. FAE1/KCS18 for seed erucic acid, CER6/KCS6 for cuticular wax), while the downstream steps are carried out by orthologs of the animal enzymes (KCR1, PAS2, ECR/CER10 in Arabidopsis). The condensation step is therefore modelled as alternative enzyme families, and the three shared steps list animal and plant exemplars.

MODULE:fatty_acid_elongation_cycleDRAFTMetabolic Pathwaymodules/fatty_acid_elongation_cycle.yaml
fatty acid elongationGO:0030497 very long-chain fatty acid biosynthetic processGO:0042761
YeastPathways:PWY-5080-1
very long chain fatty acid biosynthesis I (S. cerevisiae, SGD YeastPathways)
YeastCyc lists the four cycle reactions with ELO2/ELO3 (condensation), IFA38 (3-oxoacyl-CoA reduction), PHS1 (dehydration) and TSC13 (enoyl reduction). All assignments were retained; ELO1, the C12-C16 elongase, was added.
PMID:17719544
A molecular caliper mechanism for determining very long-chain fatty acid length.
Proteoliposomes reconstituted from an Elo elongase, a dehydratase and two reductases catalysed repeated two-carbon additions; product length was dictated by the Elo homologue present and the Elo active site faces the cytosol.
PMID:9211877
ELO2 and ELO3, homologues of the Saccharomyces cerevisiae ELO1 gene, function in fatty acid elongation and are required for sphingolipid formation.
Elo2p elongates fatty acids up to C24, Elo3p is essential for C24 to C26 conversion, and both are needed for sphingolipid synthesis.
PMID:8702485
Isolation and characterization of a gene affecting fatty acid elongation in Saccharomyces cerevisiae.
elo1 mutants fail to elongate C12-C14 fatty acids efficiently; ELO1 encodes a membrane protein.
PMID:12087109
The Saccharomyces cerevisiae YBR159w gene encodes the 3-ketoreductase of the microsomal fatty acid elongase.
YBR159w (IFA38) encodes the major 3-ketoreductase of the elongase, co-localises and co-immunoprecipitates with Elo3p and Tsc13p; AYR1 supplies residual activity.
PMID:18272525
Membrane topology and essential amino acid residues of Phs1, a 3-hydroxyacyl-CoA dehydratase involved in very long-chain fatty acid elongation.
Phs1 is the 3-hydroxyacyl-CoA dehydratase of the VLCFA elongation cycle, a six-transmembrane ER protein.
PMID:11113186
Tsc13p is required for fatty acid elongation and localizes to a novel structure at the nuclear-vacuolar interface in Saccharomyces cerevisiae.
TSC13 is required for VLCFA elongation, likely as the enoyl reductase; Tsc13p co-immunoprecipitates with Elo2p and Elo3p and localises to the ER.
GO:0030497
fatty acid elongation
ELOVLs, HSD17B12, HACD1/2 and TECR run the microsomal fatty-acid elongation cycle (GO:0030497).
GO:0042761
very long-chain fatty acid biosynthetic process
The cycle produces very-long-chain (and ultra-long-chain) fatty acids (GO:0042761).
file:human/ELOVL1/ELOVL1-ai-review.yaml
ELOVL1 gene review (human)
The condensation step (UniProtKB:Q9BW60, GO:0009922) matches the completed human ELOVL1 review.
file:human/ELOVL2/ELOVL2-ai-review.yaml
ELOVL2 gene review (human)
The PUFA condensation step (UniProtKB:Q9NXB9, GO:0009922) matches the completed human ELOVL2 review.
file:human/ELOVL3/ELOVL3-ai-review.yaml
ELOVL3 gene review (human)
The condensation step (UniProtKB:Q9HB03, GO:0009922) matches the completed human ELOVL3 review.
file:human/ELOVL4/ELOVL4-ai-review.yaml
ELOVL4 gene review (human)
The ultra-long-chain condensation step (UniProtKB:Q9GZR5, GO:0009922) matches the completed human ELOVL4 review.
file:human/ELOVL6/ELOVL6-ai-review.yaml
ELOVL6 gene review (human)
The C16->C18 condensation step (UniProtKB:Q9H5J4, GO:0009922) matches the completed human ELOVL6 review.
file:human/ELOVL7/ELOVL7-ai-review.yaml
ELOVL7 gene review (human)
The condensation step (UniProtKB:A1L3X0, GO:0009922) matches the completed human ELOVL7 review.
file:ARATH/FAE1/FAE1-ai-review.yaml
FAE1 gene review (Arabidopsis)
The plant KCS condensation variant (UniProtKB:Q38860, GO:0009922) matches the completed Arabidopsis FAE1/KCS18 review.
file:THLAR/FAE1/FAE1-ai-review.yaml
FAE1 gene review (field pennycress)
The plant KCS condensation variant (UniProtKB:V9XY07, GO:0009922) matches the pennycress FAE1 review, grounded in CRISPR knockouts that abolish seed erucic acid.
file:human/HSD17B12/HSD17B12-ai-review.yaml
HSD17B12 gene review (human)
The 3-ketoacyl-CoA reduction step (UniProtKB:Q53GQ0, GO:0141040) matches the completed human HSD17B12 review.
file:human/HACD1/HACD1-ai-review.yaml
HACD1 gene review (human)
The 3-hydroxyacyl-CoA dehydration step (UniProtKB:B0YJ81, GO:0102158) matches the completed human HACD1 review.
file:human/HACD2/HACD2-ai-review.yaml
HACD2 gene review (human)
The 3-hydroxyacyl-CoA dehydration step (UniProtKB:Q6Y1H2, GO:0102158) matches the completed human HACD2 review.
file:human/TECR/TECR-ai-review.yaml
TECR gene review (human)
The trans-2-enoyl-CoA reduction step (UniProtKB:Q9NZ01, GO:0102758) matches the completed human TECR review.
file:projects/THLAR_OILSEED/ortholog_mapping/CALLS.md
Pennycress ortholog calls (THLAR_OILSEED project)
Pennycress representative members are reciprocal-best-hit orthologs of the Arabidopsis exemplars (phmmer against UP000836841 and back against UP000006548); only clear single-copy calls with full-length gene models and a matching PANTHER family are listed.
7Nodes
4Parts
1Variant Sets
2Variants
5Annotons
4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:fatty_acid_elongation_cycle 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.

Function consistency and core coverage

27 gene-function check(s) reflected in core functions · 0 conflict(s) · 4 evidence or coverage gap(s) (36 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
elovl_activity ELOVL1 (human; sat/monounsat C22->C26)
UniProtKB:Q9BW60
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
elovl_activity ELOVL2 (human; C20/C22 PUFA)
UniProtKB:Q9NXB9
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
elovl_activity ELOVL3 (human; sat/monounsat C16-C22)
UniProtKB:Q9HB03
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
elovl_activity ELOVL4 (human; ultra-long-chain C26-C38)
UniProtKB:Q9GZR5
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
elovl_activity ELOVL6 (human; C16->C18)
UniProtKB:Q9H5J4
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
elovl_activity ELOVL7 (human; C18-C20)
UniProtKB:A1L3X0
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
elovl_activity ELO1 (Saccharomyces cerevisiae; C12-C14 -> C16-C18)
UniProtKB:P39540
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
elovl_activity ELO2 (Saccharomyces cerevisiae; up to C24)
UniProtKB:P25358
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
elovl_activity ELO3 (Saccharomyces cerevisiae; C24 -> C26)
UniProtKB:P40319
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
elovl_activity elo1 (Schizosaccharomyces pombe)
UniProtKB:Q7LKX0
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
elovl_activity elo2 (Schizosaccharomyces pombe)
UniProtKB:Q9UTF7
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
kcs_activity FAE1/KCS18 (Arabidopsis; seed C18->C20/C22)
UniProtKB:Q38860
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
kcs_activity CER6/KCS6 (Arabidopsis; epidermal wax VLCFA)
UniProtKB:Q9XF43
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
kcs_activity FAE1 (field pennycress; seed erucic acid)
UniProtKB:V9XY07
Family Representative 		fatty acid elongase activity
GO:0009922 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
kcs_activity CUT1/KCS6 (field pennycress; TAV2_LOCUS17730, 1:1 ortholog)
UniProtKB:A0AAU9SM40
Family Representative 		fatty acid elongase activity
GO:0009922 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
hsd17b12_activity HSD17B12 (human)
UniProtKB:Q53GQ0
Family Representative 		very-long-chain 3-oxoacyl-CoA reductase activity
GO:0141040 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hsd17b12_activity KCR1/GLOSSY8 (Arabidopsis; plant ortholog)
UniProtKB:Q8L9C4
Family Representative 		very-long-chain 3-oxoacyl-CoA reductase activity
GO:0141040 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hsd17b12_activity KCR1 (field pennycress; TAV2_LOCUS16128, 1:1 ortholog)
UniProtKB:A0AAU9SJ87
Family Representative 		very-long-chain 3-oxoacyl-CoA reductase activity
GO:0141040 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
hsd17b12_activity IFA38 (Saccharomyces cerevisiae)
UniProtKB:P38286
Family Representative 		very-long-chain 3-oxoacyl-CoA reductase activity
GO:0141040 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hsd17b12_activity SPAC4G9.15 (Schizosaccharomyces pombe; ifa38)
UniProtKB:Q10245
Family Representative 		very-long-chain 3-oxoacyl-CoA reductase activity
GO:0141040 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hacd_activity HACD1 (human; muscle-enriched)
UniProtKB:B0YJ81
Family Representative 		very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase activity
GO:0102158 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hacd_activity HACD2 (human; ubiquitous)
UniProtKB:Q6Y1H2
Family Representative 		very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase activity
GO:0102158 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hacd_activity PAS2/PASTICCINO2 (Arabidopsis; plant ortholog)
UniProtKB:Q8VZB2
Family Representative 		very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase activity
GO:0102158 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hacd_activity PHS1 (Saccharomyces cerevisiae)
UniProtKB:P40857
Family Representative 		very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase activity
GO:0102158 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hacd_activity phs1 (Schizosaccharomyces pombe)
UniProtKB:O14346
Family Representative 		very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase activity
GO:0102158 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tecr_activity TECR (human)
UniProtKB:Q9NZ01
Family Representative 		very-long-chain enoyl-CoA reductase activity
GO:0102758 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tecr_activity ECR/CER10 (Arabidopsis; plant ortholog)
UniProtKB:Q9M2U2
Family Representative 		very-long-chain enoyl-CoA reductase activity
GO:0102758 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tecr_activity ECR (field pennycress; TAV2_LOCUS15241, 1:1 ortholog)
UniProtKB:A0AAU9SFC3
Family Representative 		very-long-chain enoyl-CoA reductase activity
GO:0102758 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
tecr_activity TSC13 (Saccharomyces cerevisiae)
UniProtKB:Q99190
Family Representative 		very-long-chain enoyl-CoA reductase activity
GO:0102758 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tecr_activity tsc13 (Schizosaccharomyces pombe)
UniProtKB:O94511
Family Representative 		very-long-chain enoyl-CoA reductase activity
GO:0102758 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
elovl_activity ELOVL / ELO fatty-acid elongase family
PANTHER:PTHR11157
Family 		fatty acid elongase activity
GO:0009922 		Family Supported
Family review supports GO:0009922 FAMILY_WIDE. Asserted by fatty_acid_elongation_cycle; accepted by every reviewed fungal and mammalian elongase.
kcs_activity plant 3-ketoacyl-CoA synthase (KCS/FAE1) family
PANTHER:PTHR31561
Family 		fatty acid elongase activity
GO:0009922 		Family Supported
Family review supports GO:0009922 FAMILY_WIDE. Asserted by fatty_acid_elongation_cycle; accepted by FAE1 (Arabidopsis and Thlaspi) and CUT1.
hsd17b12_activity very-long-chain 3-ketoacyl-CoA reductase (KAR; SDR superfamily)
Family 		very-long-chain 3-oxoacyl-CoA reductase activity
GO:0141040 		Family Id Missing
The family has no identifier linking it to a curated family review.
hacd_activity HACD / 3-hydroxyacyl-CoA dehydratase family
PANTHER:PTHR11035
Family 		very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase activity
GO:0102158 		Family Supported
Family review supports GO:0102158 FAMILY_WIDE. Asserted by fatty_acid_elongation_cycle; core function of every reviewed member.
tecr_activity TECR / trans-2-enoyl-CoA reductase family
PANTHER:PTHR10556:SF28
Family 		very-long-chain enoyl-CoA reductase activity
GO:0102758 		Family Supported
Family review supports GO:0102758 for PANTHER:PTHR10556:SF28. Enoyl-CoA reductases only (SF28, SF31). fatty_acid_elongation_cycle selects the base family, which also takes in the steroid 5-alpha-reductases.
tecr_activity TECR / trans-2-enoyl-CoA reductase family
PANTHER:PTHR10556:SF31
Family 		very-long-chain enoyl-CoA reductase activity
GO:0102758 		Family Supported
Family review supports GO:0102758 for PANTHER:PTHR10556:SF31. Enoyl-CoA reductases only (SF28, SF31). fatty_acid_elongation_cycle selects the base family, which also takes in the steroid 5-alpha-reductases.

Gene-review completeness (27/30 grounded genes reviewed)

25 complete review(s) · 12 with deep research · 3 missing review · 15 reviewed but lacking deep research

Gene Review Complete Deep research
ECR (field pennycress; TAV2_LOCUS15241, 1:1 ortholog) A0AAU9SFC3 ✗ — —
KCR1 (field pennycress; TAV2_LOCUS16128, 1:1 ortholog) A0AAU9SJ87 ✗ — —
CUT1/KCS6 (field pennycress; TAV2_LOCUS17730, 1:1 ortholog) A0AAU9SM40 ✗ — —
CUT1 Q9XF43 ✓ ✓ ✓
ECR Q9M2U2 ✓ ✓ ✓
ELO1 P39540 ✓ ✓ ✓
elo1 Q7LKX0 ✓ ✓ ✗
ELO2 P25358 ✓ ✓ ✓
elo2 Q9UTF7 ✓ ✓ ✗
ELO3 P40319 ✓ ✓ ✓
ELOVL1 Q9BW60 ✓ ✓ ✗
ELOVL2 Q9NXB9 ✓ 40/44 ✗
ELOVL3 Q9HB03 ✓ ✓ ✗
ELOVL4 Q9GZR5 ✓ 33/37 ✗
ELOVL6 Q9H5J4 ✓ ✓ ✗
ELOVL7 A1L3X0 ✓ ✓ ✗
FAE1 Q38860 ✓ ✓ ✓
FAE1 V9XY07 ✓ ✓ ✓
HACD1 B0YJ81 ✓ ✓ ✗
HACD2 Q6Y1H2 ✓ ✓ ✗
HSD17B12 Q53GQ0 ✓ ✓ ✗
IFA38 P38286 ✓ ✓ ✓
ifa38 Q10245 ✓ ✓ ✗
KCR1 Q8L9C4 ✓ ✓ ✓
PAS2 Q8VZB2 ✓ ✓ ✓
phs1 O14346 ✓ ✓ ✗
PHS1 P40857 ✓ ✓ ✓
TECR Q9NZ01 ✓ ✓ ✗
tsc13 O94511 ✓ ✓ ✗
TSC13 Q99190 ✓ ✓ ✓

Details

Context
endoplasmic reticulum membraneGO:0005789
Microsomal fatty-acid elongation cycleMetabolic Pathwayfatty_acid_elongation_cycle
fatty acid elongationGO:0030497 very long-chain fatty acid biosynthetic processGO:0042761
Context
endoplasmic reticulum membraneGO:0005789

Microsomal fatty-acid elongation cycle (GO:0030497 + GO:0042761), grounded to ten completed human gene reviews plus Arabidopsis (FAE1, CUT1, KCR1, PAS2, ECR) and field pennycress (FAE1) reviews, with pennycress orthologs as additional examples; all ER-membrane enzymes of the fatty acid elongase complex (GO:0009923). CONDENSATION (rate-limiting, substrate-selective): six of the seven ELOVLs reviewed here (ELOVL1 Q9BW60, ELOVL2 Q9NXB9, ELOVL3 Q9HB03, ELOVL4 Q9GZR5, ELOVL6 Q9H5J4, ELOVL7 A1L3X0) share PTHR11157 and all carry GO:0009922 fatty acid elongase activity (the single correct MF — no finer chain-length GO term exists; specificity noted per-gene: ELOVL6 C16->C18, ELOVL1 sat/monounsat VLCFA, ELOVL2 C20/C22 PUFA->DHA, ELOVL3 skin/brown-fat, ELOVL4 ultra-long-chain C26-C38, ELOVL7 C18-C20; ELOVL5 already reviewed earlier). The other three steps are SHARED across all ELOVLs: HSD17B12/KAR (Q53GQ0 PTHR43899, GO:0141040 3-oxoacyl-CoA reductase — its legacy 17-beta-HSD/estradiol activity is non-core), HACD1 (B0YJ81, muscle) + HACD2 (Q6Y1H2, ubiquitous) sharing PTHR11035 (GO:0102158 (3R)-3-hydroxyacyl-CoA dehydratase), and TECR (Q9NZ01 PTHR10556, GO:0102758 trans-2-enoyl-CoA reductase). Recurrent curation note: several reviews flag PMID:10970790 (HELO1 = the ELOVL5/ELOVL2 clone) as a WRONG_IDENTIFIER Reactome-EXP source though the elongase MF itself is correct. GO term ids/labels verified against the local go.db. Products feed sphingolipid/ceramide synthesis (curated modules), membrane phospholipids and skin/myelin/retina lipids. Disorders: ELOVL1 IKSHD; ELOVL4 Stargardt-like STGD3 / SCA34 / ISQMR; HACD1 congenital myopathy; TECR intellectual disability (MRT14). ALIGN (YeastPathways project, 2026-10): S. cerevisiae and S. pombe exemplars were added to all four steps. YeastCyc PWY-5080-1 lists ELO2, ELO3, IFA38, PHS1 and TSC13, all retained; ELO1 (C12-C14 -> C16-C18, PMID:8702485) was added as the third yeast elongase, and the minor ketoreductase AYR1 (PMID:12087109) is noted but not listed as a representative. All five fungal elongases are in PTHR11157 with the ELOVLs. The ketoreductase descriptor lost its PANTHER id (PTHR43899 "RH59310P") because the fungal orthologues IFA38 and SPAC4G9.15 are in PTHR43086. PHS1/phs1 (PTHR11035) and TSC13/tsc13 (PTHR10556) fit the existing families. GO-CAM disagreements: YeastPathways_PWY-5080-1 places every activity in cytosol rather than ER membrane, types IFA38 as GO:0018454 acetoacetyl-CoA reductase and PHS1 as GO:0004300 enoyl-CoA hydratase rather than the very-long-chain terms, and omits ELO1; the PomBase model uses the broader GO:0018812 and GO:0019166 for phs1 and tsc13 but otherwise agrees.

Connections

condensation -> ketoreduction Provides Input For
The 3-oxoacyl-CoA made by the condensing enzyme (ELOVL or KCS) is reduced by HSD17B12 (KCR1 in plants).
ketoreduction -> dehydration Provides Input For
The (3R)-3-hydroxyacyl-CoA is dehydrated by HACD1/HACD2.
dehydration -> enoyl_reduction Provides Input For
The (2E)-enoyl-CoA is reduced by TECR.
enoyl_reduction -> condensation Provides Input For
The 2-carbon-elongated saturated acyl-CoA re-enters the condensation step, iterating the cycle until the target chain length is reached.
Part 1: condensation (rate-limiting; substrate selectivity)
Condensing enzyme (ELOVL or 3-ketoacyl-CoA synthase)Reactioncondensation

The condensation of acyl-CoA with malonyl-CoA is carried out by two unrelated enzyme families that converged on the same reaction (GO:0009922): the membrane-embedded ELO/ELOVL elongases of animals and fungi, and the thiolase-fold 3-ketoacyl-CoA synthases (KCS/FAE1) of plants. The downstream reductase, dehydratase and reductase steps are homologous across both lineages.

Variant set: ELO/ELOVL (animals, fungi) vs KCS/FAE1 (plants) condensing enzymes by enzyme family / taxon (One Or More)
ELO/ELOVL fatty-acid elongases (animals, fungi)Reactionelovl_condensation

Annotons

ELOVL1/2/3/4/6/7: fatty acid elongase (condensing enzyme)
elovl_activity
Participant: Family: ELOVL / ELO fatty-acid elongase family
Family:
ELOVL / ELO fatty-acid elongase familyPANTHER:PTHR11157
Representative Members: ELOVL1 (human; sat/monounsat C22->C26)UniProtKB:Q9BW60 ELOVL2 (human; C20/C22 PUFA)UniProtKB:Q9NXB9 ELOVL3 (human; sat/monounsat C16-C22)UniProtKB:Q9HB03 ELOVL4 (human; ultra-long-chain C26-C38)UniProtKB:Q9GZR5 ELOVL6 (human; C16->C18)UniProtKB:Q9H5J4 ELOVL7 (human; C18-C20)UniProtKB:A1L3X0 ELO1 (Saccharomyces cerevisiae; C12-C14 -> C16-C18)UniProtKB:P39540 ELO2 (Saccharomyces cerevisiae; up to C24)UniProtKB:P25358 ELO3 (Saccharomyces cerevisiae; C24 -> C26)UniProtKB:P40319 elo1 (Schizosaccharomyces pombe)UniProtKB:Q7LKX0 elo2 (Schizosaccharomyces pombe)UniProtKB:Q9UTF7

Function

fatty acid elongase activityGO:0009922
Substrates: acyl-CoA (chain-length/saturation per ELOVL isoform) malonyl-CoA
Products: 3-oxoacyl-CoA (2 carbons longer) CO2 + CoA

Locations

endoplasmic reticulum membraneGO:0005789

Condense acyl-CoA + malonyl-CoA to 3-oxoacyl-CoA (rate-limiting; sets specificity).

Plant 3-ketoacyl-CoA synthases (KCS / FAE1)Reactionkcs_condensation

Annotons

KCS/FAE1: 3-ketoacyl-CoA synthase (plant condensing enzyme)
kcs_activity
Participant: Family: plant 3-ketoacyl-CoA synthase (KCS/FAE1) family
Family:
plant 3-ketoacyl-CoA synthase (KCS/FAE1) familyPANTHER:PTHR31561
Representative Members: FAE1/KCS18 (Arabidopsis; seed C18->C20/C22)UniProtKB:Q38860 CER6/KCS6 (Arabidopsis; epidermal wax VLCFA)UniProtKB:Q9XF43 FAE1 (field pennycress; seed erucic acid)UniProtKB:V9XY07 CUT1/KCS6 (field pennycress; TAV2_LOCUS17730, 1:1 ortholog)UniProtKB:A0AAU9SM40

Function

fatty acid elongase activityGO:0009922
Substrates: acyl-CoA (C16-C18 and longer; chain length per KCS paralog) malonyl-CoA
Products: 3-oxoacyl-CoA (2 carbons longer) CO2 + CoA

Locations

endoplasmic reticulum membraneGO:0005789

Condense acyl-CoA + malonyl-CoA to 3-oxoacyl-CoA; the KCS paralog sets chain length and tissue (seed oil, cuticular wax, suberin).

Part 2: 3-ketoacyl-CoA reduction
3-ketoacyl-CoA reductase (HSD17B12 / KAR)Reactionketoreduction

Annotons

HSD17B12: very-long-chain 3-oxoacyl-CoA reductase
hsd17b12_activity
Participant: Family: very-long-chain 3-ketoacyl-CoA reductase (KAR; SDR superfamily)
Family:
very-long-chain 3-ketoacyl-CoA reductase (KAR; SDR superfamily) No PANTHER id: animal HSD17B12 and plant KCR1 are in PTHR43899, whereas the fungal orthologues IFA38 and S. pombe SPAC4G9.15 are in PTHR43086, so no single family contains all representatives.
Representative Members: HSD17B12 (human)UniProtKB:Q53GQ0 KCR1/GLOSSY8 (Arabidopsis; plant ortholog)UniProtKB:Q8L9C4 KCR1 (field pennycress; TAV2_LOCUS16128, 1:1 ortholog)UniProtKB:A0AAU9SJ87 IFA38 (Saccharomyces cerevisiae)UniProtKB:P38286 SPAC4G9.15 (Schizosaccharomyces pombe; ifa38)UniProtKB:Q10245

Function

very-long-chain 3-oxoacyl-CoA reductase activityGO:0141040
Substrates: 3-oxoacyl-CoA NADPH
Products: (3R)-3-hydroxyacyl-CoA NADP+

Locations

endoplasmic reticulum membraneGO:0005789

Reduce 3-oxoacyl-CoA to (3R)-3-hydroxyacyl-CoA (NADPH).

Part 3: 3-hydroxyacyl-CoA dehydration
3-hydroxyacyl-CoA dehydratase (HACD1/HACD2)Reactiondehydration

Annotons

HACD1/HACD2: very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase
hacd_activity
Participant: Family: HACD / 3-hydroxyacyl-CoA dehydratase family
Family:
HACD / 3-hydroxyacyl-CoA dehydratase familyPANTHER:PTHR11035
Representative Members: HACD1 (human; muscle-enriched)UniProtKB:B0YJ81 HACD2 (human; ubiquitous)UniProtKB:Q6Y1H2 PAS2/PASTICCINO2 (Arabidopsis; plant ortholog)UniProtKB:Q8VZB2 PHS1 (Saccharomyces cerevisiae)UniProtKB:P40857 phs1 (Schizosaccharomyces pombe)UniProtKB:O14346

Function

very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase activityGO:0102158
Substrates: (3R)-3-hydroxyacyl-CoA
Products: (2E)-enoyl-CoA H2O

Locations

endoplasmic reticulum membraneGO:0005789

Dehydrate (3R)-3-hydroxyacyl-CoA to (2E)-enoyl-CoA.

Part 4: trans-2-enoyl-CoA reduction (cycle completion)
trans-2-enoyl-CoA reductase (TECR)Reactionenoyl_reduction

Annotons

TECR: very-long-chain trans-2-enoyl-CoA reductase
tecr_activity
Participant: Family: TECR / trans-2-enoyl-CoA reductase family
Family:
TECR / trans-2-enoyl-CoA reductase family
Representative Members: TECR (human)UniProtKB:Q9NZ01 ECR/CER10 (Arabidopsis; plant ortholog)UniProtKB:Q9M2U2 ECR (field pennycress; TAV2_LOCUS15241, 1:1 ortholog)UniProtKB:A0AAU9SFC3 TSC13 (Saccharomyces cerevisiae)UniProtKB:Q99190 tsc13 (Schizosaccharomyces pombe)UniProtKB:O94511

Function

very-long-chain enoyl-CoA reductase activityGO:0102758
Substrates: (2E)-enoyl-CoA NADPH
Products: acyl-CoA (fully saturated, 2 carbons longer) NADP+

Locations

endoplasmic reticulum membraneGO:0005789

Reduce (2E)-enoyl-CoA to the elongated saturated acyl-CoA (NADPH; completes cycle).