CEM1 (YER061C) encodes the mitochondrial beta-ketoacyl-[acyl-carrier-protein] synthase (KAS, EC 2.3.1.41) of S. cerevisiae, a FabF-like member of the thiolase superfamily. Within the matrix it catalyses the Claisen condensation of acyl-ACP with malonyl-ACP (on the mitochondrial ACP, Acp1) to form 3-oxoacyl-ACP, the chain-extending step of the bacterial-like type II mitochondrial fatty acid synthase (mtFAS) that also comprises Hfa1, Mct1, Oar1, Htd2 and Etr1. mtFAS produces octanoyl-ACP, the precursor of lipoic acid needed for lipoylation of pyruvate and 2-oxoglutarate dehydrogenases, together with longer acyl chains needed for respiratory competence. cem1 null mutants are respiratory deficient with lowered lipoic acid levels, a defect complemented by the human mitochondrial KAS OXSM.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the FabF/KAS II node PTN000918584 (E. coli FabF/FabB, Arabidopsis plastid/mitochondrial KAS). Cem1 is the yeast mitochondrial KAS of this clade; core MF. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt SIMILARITY: Belongs to the thiolase-like superfamily. Beta-ketoacyl-ACP PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA via RHEA:22836 / EC 2.3.1.41 and the beta-ketoacyl synthase active-site signature IPR018201. Correct for Cem1. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt Reaction=a fatty acyl-[ACP] + malonyl-[ACP] + H(+) = a 3-oxoacyl-[ACP] |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | ISA PMID:15668256 Cloning, expression, and characterization of the human mitoc... | ACCEPT | Summary: ISA with human OXSM (Q9NWU1; Zhang et al. 2005): human mitochondrial KAS, which has KAS activity with mitochondrial ACP substrates, complements the respiratory defect and lipoic acid deficiency of cem1. Core MF. Supporting Evidence: PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels PMID:15668256 The enzyme can elongate acyl-chains containing 2-14 carbon atoms with malonyl moieties attached in thioester linkage to the human mitochondrial acyl carrier protein |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways FASYN-ELONG2-PWY (fatty acid elongation (saturated, ACP-bound)). The KAS activity is correct for Cem1, but YeastPathways places it in a cytosolic FAS pathway; the cytosolic condensation step is performed by the KS domain of Fas2, while Cem1 acts in mitochondrial type II FAS. MF accepted; compartment/pathway context wrong. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt Reaction=a fatty acyl-[ACP] + malonyl-[ACP] + H(+) = a 3-oxoacyl-[ACP] PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-10 (fatty acid biosynthesis, initial steps). The KAS activity is correct for Cem1, but YeastPathways places it in a cytosolic FAS pathway; the cytosolic condensation step is performed by the KS domain of Fas2, while Cem1 acts in mitochondrial type II FAS. MF accepted; compartment/pathway context wrong. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt Reaction=a fatty acyl-[ACP] + malonyl-[ACP] + H(+) = a 3-oxoacyl-[ACP] PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-355 (stearate biosynthesis III (fungi)). The KAS activity is correct for Cem1, but YeastPathways places it in a cytosolic FAS pathway; the cytosolic condensation step is performed by the KS domain of Fas2, while Cem1 acts in mitochondrial type II FAS. MF accepted; compartment/pathway context wrong. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt Reaction=a fatty acyl-[ACP] + malonyl-[ACP] + H(+) = a 3-oxoacyl-[ACP] PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-5962 (superpathway of fatty acid biosynthesis, saturated and unsaturated). The KAS activity is correct for Cem1, but YeastPathways places it in a cytosolic FAS pathway; the cytosolic condensation step is performed by the KS domain of Fas2, while Cem1 acts in mitochondrial type II FAS. MF accepted; compartment/pathway context wrong. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt Reaction=a fatty acyl-[ACP] + malonyl-[ACP] + H(+) = a 3-oxoacyl-[ACP] PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-6336 (superpathway of fatty acid biosynthesis, saturated). The KAS activity is correct for Cem1, but YeastPathways places it in a cytosolic FAS pathway; the cytosolic condensation step is performed by the KS domain of Fas2, while Cem1 acts in mitochondrial type II FAS. MF accepted; compartment/pathway context wrong. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt Reaction=a fatty acyl-[ACP] + malonyl-[ACP] + H(+) = a 3-oxoacyl-[ACP] PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels |
| GO:0005739 mitochondrion | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: HDA (PMID:14562095) detecting Cem1 in mitochondria (GFP imaging or mitochondrial proteomics). Consistent with its role in mitochondrial FAS; core location. Supporting Evidence: PMID:14562095 Global analysis of protein localization in budding yeast. PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: HDA (PMID:16823961) detecting Cem1 in mitochondria (GFP imaging or mitochondrial proteomics). Consistent with its role in mitochondrial FAS; core location. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: HDA (PMID:24769239) detecting Cem1 in mitochondria (GFP imaging or mitochondrial proteomics). Consistent with its role in mitochondrial FAS; core location. Supporting Evidence: PMID:24769239 quantitative proteomic and phosphoproteomic study of isolated mitochondria PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (is_active_in) from PTN000918585 (human OXSM, trypanosome mtKAS). Correct for Cem1. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (Mitochondrion). Correct. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways FASYN-ELONG2-PWY (fatty acid elongation (saturated, ACP-bound)) placing Cem1 in the cytosolic fatty acid pathway. Cem1 is a mitochondrial enzyme (mtFAS); the cytosolic KAS step is catalysed by Fas2. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels PMID:9388293 as is the case for the genes encoding a mitochondrial acyl carrier protein and a beta-ketoacyl-ACP synthase |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways PWY3O-10 (fatty acid biosynthesis, initial steps) placing Cem1 in the cytosolic fatty acid pathway. Cem1 is a mitochondrial enzyme (mtFAS); the cytosolic KAS step is catalysed by Fas2. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels PMID:9388293 as is the case for the genes encoding a mitochondrial acyl carrier protein and a beta-ketoacyl-ACP synthase |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways PWY3O-355 (stearate biosynthesis III (fungi)) placing Cem1 in the cytosolic fatty acid pathway. Cem1 is a mitochondrial enzyme (mtFAS); the cytosolic KAS step is catalysed by Fas2. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels PMID:9388293 as is the case for the genes encoding a mitochondrial acyl carrier protein and a beta-ketoacyl-ACP synthase |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways PWY3O-5962 (superpathway of fatty acid biosynthesis, saturated and unsaturated) placing Cem1 in the cytosolic fatty acid pathway. Cem1 is a mitochondrial enzyme (mtFAS); the cytosolic KAS step is catalysed by Fas2. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels PMID:9388293 as is the case for the genes encoding a mitochondrial acyl carrier protein and a beta-ketoacyl-ACP synthase |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: RCA (is_active_in) from YeastPathways PWY3O-6336 (superpathway of fatty acid biosynthesis, saturated) placing Cem1 in the cytosolic fatty acid pathway. Cem1 is a mitochondrial enzyme (mtFAS); the cytosolic KAS step is catalysed by Fas2. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels PMID:9388293 as is the case for the genes encoding a mitochondrial acyl carrier protein and a beta-ketoacyl-ACP synthase |
| GO:0006633 fatty acid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000918584 (bacterial and plant KAS). Cem1 catalyses the condensation step of mitochondrial type II FAS; correct, core BP. Supporting Evidence: PMID:15668256 The enzyme can elongate acyl-chains containing 2-14 carbon atoms with malonyl moieties attached in thioester linkage to the human mitochondrial acyl carrier protein PMID:9388293 as is the case for the genes encoding a mitochondrial acyl carrier protein and a beta-ketoacyl-ACP synthase |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: IEA from InterPro IPR018201 (beta-ketoacyl synthase active site). Correct. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt Reaction=a fatty acyl-[ACP] + malonyl-[ACP] + H(+) = a 3-oxoacyl-[ACP] |
| GO:0006633 fatty acid biosynthetic process | ISA PMID:15668256 Cloning, expression, and characterization of the human mitoc... | ACCEPT | Summary: ISA with human OXSM (Zhang et al. 2005). Correct; mtFAS. Supporting Evidence: PMID:15668256 The enzyme can elongate acyl-chains containing 2-14 carbon atoms with malonyl moieties attached in thioester linkage to the human mitochondrial acyl carrier protein PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels |
| GO:0006633 fatty acid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-10 (fatty acid biosynthesis, initial steps). Cem1 participates in fatty acid biosynthesis, but in mitochondria (mtFAS) rather than the cytosolic pathway named; the BP term itself is correct. Supporting Evidence: PMID:15668256 The enzyme can elongate acyl-chains containing 2-14 carbon atoms with malonyl moieties attached in thioester linkage to the human mitochondrial acyl carrier protein PMID:9388293 as is the case for the genes encoding a mitochondrial acyl carrier protein and a beta-ketoacyl-ACP synthase |
| GO:0006633 fatty acid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-355 (stearate biosynthesis III (fungi)). Cem1 participates in fatty acid biosynthesis, but in mitochondria (mtFAS) rather than the cytosolic pathway named; the BP term itself is correct. Supporting Evidence: PMID:15668256 The enzyme can elongate acyl-chains containing 2-14 carbon atoms with malonyl moieties attached in thioester linkage to the human mitochondrial acyl carrier protein PMID:9388293 as is the case for the genes encoding a mitochondrial acyl carrier protein and a beta-ketoacyl-ACP synthase |
| GO:0006633 fatty acid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-5962 (superpathway of fatty acid biosynthesis, saturated and unsaturated). Cem1 participates in fatty acid biosynthesis, but in mitochondria (mtFAS) rather than the cytosolic pathway named; the BP term itself is correct. Supporting Evidence: PMID:15668256 The enzyme can elongate acyl-chains containing 2-14 carbon atoms with malonyl moieties attached in thioester linkage to the human mitochondrial acyl carrier protein PMID:9388293 as is the case for the genes encoding a mitochondrial acyl carrier protein and a beta-ketoacyl-ACP synthase |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: IEA from InterPro IPR016039 (thiolase-like). Correct but uninformative parent of 3-oxoacyl-ACP synthase activity. Reason: Uninformative parent of the core MF. Supporting Evidence: file:yeast/CEM1/CEM1-uniprot.txt SIMILARITY: Belongs to the thiolase-like superfamily. Beta-ketoacyl-ACP |
| GO:0019367 fatty acid elongation, saturated fatty acid | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: RCA from YeastPathways PWY3O-6336 (superpathway of fatty acid biosynthesis, saturated), a cytosolic FAS/elongation pathway. Cem1 elongates acyl-ACP chains within mitochondrial FAS (principally to the octanoyl lipoate precursor), which is captured by fatty acid biosynthetic process; it has no role in the cytosolic elongation/stearate pathway from which this term was inferred. Reason: Inherited from a cytosolic pathway; mtFAS chain extension is covered by fatty acid biosynthetic process. Supporting Evidence: PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels PMID:19571038 Mitochondrial fatty acid synthesis (FAS) generates the octanoyl-group that is required for the synthesis of lipoic acid |
| GO:0030497 fatty acid elongation | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: RCA from YeastPathways FASYN-ELONG2-PWY (fatty acid elongation (saturated, ACP-bound)), a cytosolic FAS/elongation pathway. Cem1 elongates acyl-ACP chains within mitochondrial FAS (principally to the octanoyl lipoate precursor), which is captured by fatty acid biosynthetic process; it has no role in the cytosolic elongation/stearate pathway from which this term was inferred. Reason: Inherited from a cytosolic pathway; mtFAS chain extension is covered by fatty acid biosynthetic process. Supporting Evidence: PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels PMID:19571038 Mitochondrial fatty acid synthesis (FAS) generates the octanoyl-group that is required for the synthesis of lipoic acid |
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Download this section (compressed HTML)Q: What is the chain-length specificity of yeast Cem1 itself (no direct enzymology on the yeast protein is cached), and does it limit mtFAS output to C8 versus longer chains?
Experiment: Purify Cem1 and assay condensation with yeast holo-Acp1-bound acyl substrates of different chain lengths (C2-C14).
Mitochondrial beta-keto-acyl synthase; possible role in fatty acid synthesis; required for mitochondrial respiration; human homolog OXSM can complement yeast cem1 null mutant
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