FAA4 (YMR246W) encodes a long-chain fatty acyl-CoA synthetase (ACSL family, EC 6.2.1.3), the closest paralog of Faa1p in Saccharomyces cerevisiae. Purified Faa4p prefers myristate among saturated fatty acids and strongly favours cis-9 monounsaturated C14-C18 fatty acids, and it is relatively sensitive to triacsin C. Faa4p is partially redundant with Faa1p: faa1 faa4 double mutants lack most long-chain acyl-CoA synthetase activity toward oleate, are severely impaired in long-chain fatty acid import, have depleted acyl-CoA pools and reduced oxidation of exogenous oleate. Faa4p forms a complex with Fat1p for vectorial acylation, activates hexadecenoic acid in the sphingolipid-to-glycerolipid pathway, and contributes weakly to uptake of sphingoid long-chain bases. Faa4p resides in the ER and on lipid droplets, relocalising from the ER to the lipid droplet surface on entry into stationary phase where it supplies acyl-CoA for triacylglycerol synthesis; a minor pool is at the plasma membrane.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001676 long-chain fatty acid metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for long-chain fatty acid metabolic process from ACSL node PTN000645126; Faa4p activates long-chain fatty acids. Supporting Evidence: PMID:7650027 Among C8-C18 saturated fatty acids, Faa4p and Faa1p both prefer C14:0 PMID:11477098 These studies demonstrated oleoyl CoA levels were reduced to less than 10% wild-type levels in faa1 Delta and faa1 Delta faa4 Delta strains |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for long-chain fatty acid-CoA ligase from the broad ACSL node; consistent with purified Faa4p activity. Supporting Evidence: PMID:7650027 Among C8-C18 saturated fatty acids, Faa4p and Faa1p both prefer C14:0 |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IDA PMID:7650027 Comparison of the reactivity of tetradecenoic acids, a triac... | ACCEPT | Summary: IDA (Knoll et al. 1995): purified Faa4p activates C8-C18 fatty acids, preferring myristate and cis-9 monounsaturated fatty acids. Supporting Evidence: PMID:7650027 We have now purified Faa4p from S. cerevisiae and compared its fatty acid substrate specificity in vitro with the specificities of purified Faa1p, Faa2p, and Faa3p PMID:7650027 Among C8-C18 saturated fatty acids, Faa4p and Faa1p both prefer C14:0 PMID:7650027 Faa4p's selectivity for fatty acids with a C9-C10 cis-double bond is a feature it shares with Faa3p |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA from Rhea/EC 6.2.1.3 mappings; matches experimental activity. Supporting Evidence: file:yeast/FAA4/FAA4-uniprot.txt Reaction=a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl- |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IGI PMID:11477098 The Acyl-CoA synthetases encoded within FAA1 and FAA4 in Sac... | ACCEPT | Summary: IGI with FAA1 (Faergeman et al. 2001): oleoyl-CoA formation from exogenous oleate falls further in faa1 faa4 cells, revealing Faa4p's redundant ligase activity. Supporting Evidence: PMID:11477098 These studies demonstrated oleoyl CoA levels were reduced to less than 10% wild-type levels in faa1 Delta and faa1 Delta faa4 Delta strains |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IGI PMID:22633490 The SjΓΆgren-Larsson syndrome gene encodes a hexadecenal dehy... | ACCEPT | Summary: IGI with FAA1 (Nakahara et al. 2012): Faa1 and Faa4 activate hexadecenoic acid in the sphingolipid-to-glycerolipid pathway. Supporting Evidence: PMID:22633490 we demonstrate that yeast Faa1 and Faa4 and mammalian ACSL family members are acyl-CoA synthetases involved in the sphingolipid-to-glycerolipid metabolic pathway |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IMP PMID:11477098 The Acyl-CoA synthetases encoded within FAA1 and FAA4 in Sac... | ACCEPT | Summary: IMP (Faergeman et al. 2001) for long-chain acyl-CoA synthetase activity, from analysis of faa4 mutants in the faa1 background. Supporting Evidence: PMID:11477098 These studies demonstrated oleoyl CoA levels were reduced to less than 10% wild-type levels in faa1 Delta and faa1 Delta faa4 Delta strains PMID:11477098 The faa1 Delta faa4 Delta strain had a marked reduction in endogenous acyl-CoA pools, suggesting these enzymes play a role in maintenance of endogenous acyl-CoA pools, metabolism and trafficking |
| GO:0004467 long-chain fatty acid-CoA ligase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (YEAST-FAO-PWY) for the EC 6.2.1.3 step. Activity correct; Faa4p acts on the ER/LD cytoplasmic face upstream of Pxa1/Pxa2-mediated acyl-CoA import, not inside peroxisomes. Supporting Evidence: PMID:7650027 Among C8-C18 saturated fatty acids, Faa4p and Faa1p both prefer C14:0 PMID:11477098 this strain had levels of in vivo beta-oxidation of exogenous oleate reduced 3-fold when compared with the isogenic parent |
| GO:0005737 cytoplasm | HDA PMID:11914276 Subcellular localization of the yeast proteome. | TOO GENERAL | Summary: HDA from a genome-wide immunolocalisation study (Kumar et al. 2002). Cytoplasm is correct in the broad sense (ER, lipid droplets), but less informative than the established locations. Supporting Evidence: PMID:34161133 Faa4 as well as the diacylglycerol acyltransferase Dga1, which produces TAGs, are localized to the ER membrane where LDs emerge |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for ER (is_active_in) from the ACSL node; consistent with live-cell imaging placing Faa4p in the ER membrane during growth. Supporting Evidence: PMID:34161133 Faa4 as well as the diacylglycerol acyltransferase Dga1, which produces TAGs, are localized to the ER membrane where LDs emerge |
| GO:0005811 lipid droplet | EXP PMID:21820081 Lipid particles/droplets of the yeast Saccharomyces cerevisi... | ACCEPT | Summary: EXP from the lipid droplet proteome/lipidome study of Grillitsch et al. 2011. Supporting Evidence: file:yeast/FAA4/FAA4-uniprot.txt SUBCELLULAR LOCATION: Lipid droplet |
| GO:0005811 lipid droplet | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for lipid droplet from node PTN000645126; correct for Faa4p. Supporting Evidence: PMID:10515935 In addition, several proteins with known function could be attributed to the lipid particle fraction during this study, namely Erg7p, Faa1p, Faa4p, and Fat1p |
| GO:0005811 lipid droplet | IDA PMID:10515935 Identification and characterization of major lipid particle ... | ACCEPT | Summary: IDA (Athenstaedt et al. 1999): Faa4p identified in the lipid particle fraction. Supporting Evidence: PMID:10515935 In addition, several proteins with known function could be attributed to the lipid particle fraction during this study, namely Erg7p, Faa1p, Faa4p, and Fat1p |
| GO:0005811 lipid droplet | IDA PMID:24868093 High confidence proteomic analysis of yeast LDs identifies a... | ACCEPT | Summary: IDA (Currie et al. 2014): Faa4 is among the proteins detected in all yeast LD proteomes. Supporting Evidence: PMID:24868093 Twelve proteins (Ayr1, Eht1, Erg1, Erg6, Erg7, Faa1, Faa4, Fat1, Pet10, Slc1, Tgl1, and Tgl3) were detected in the current work and all reported proteomes |
| GO:0005811 lipid droplet | IDA PMID:34161133 Quantitative live-cell PALM reveals nanoscopic Faa4 redistri... | ACCEPT | Summary: IDA (Adhikari et al. 2021): quantitative PALM shows Faa4 relocalising from the ER to lipid droplet surfaces in stationary phase. Supporting Evidence: PMID:34161133 During nutrient deprivation when yeast cells reach a stationary growth phase, Dga1 and Faa4 dynamically relocalize from the ER to the surface of LDs |
| GO:0005811 lipid droplet | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0154, lipid droplet); consistent with experimental data. Supporting Evidence: file:yeast/FAA4/FAA4-uniprot.txt SUBCELLULAR LOCATION: Lipid droplet |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways RCA default cytosol compartment for the activation step. Faa4p is observed on ER, lipid droplets and plasma membrane rather than as a soluble cytosolic enzyme. Supporting Evidence: PMID:34161133 Faa4 as well as the diacylglycerol acyltransferase Dga1, which produces TAGs, are localized to the ER membrane where LDs emerge |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for plasma membrane from the fungal ACSL node; supported by partial plasma membrane localisation of Faa4-GFP. Supporting Evidence: PMID:27136724 Faa4-GFP was also localized in the plasma membrane but only partly; most of it was localized in internal organelles |
| GO:0005886 plasma membrane | IDA PMID:27136724 Long-chain bases of sphingolipids are transported into cells... | ACCEPT | Summary: IDA (Narita et al. 2016): Faa4-GFP partly at the plasma membrane, most in internal organelles. Supporting Evidence: PMID:27136724 Faa4-GFP was also localized in the plasma membrane but only partly; most of it was localized in internal organelles |
| GO:0010494 cytoplasmic stress granule | HDA PMID:26777405 ATPase-Modulated Stress Granules Contain a Diverse Proteome ... | KEEP AS NON CORE | Summary: HDA from the stress granule proteome of Jain et al. 2016. A single proteomic detection in a condition-specific structure without functional follow-up; not related to Faa4p's known role. |
| GO:0016405 CoA-ligase activity | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA for CoA-ligase activity; correct but too general. The activity is long-chain fatty acid-CoA ligase. Proposed replacements: long-chain fatty acid-CoA ligase activity Supporting Evidence: PMID:7650027 Among C8-C18 saturated fatty acids, Faa4p and Faa1p both prefer C14:0 |
| GO:0019395 fatty acid oxidation | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA for fatty acid oxidation. faa1 faa4 cells oxidise exogenous oleate 3-fold less, so Faa4p contributes by supplying acyl-CoA for peroxisomal import, but its main roles are fatty acid uptake and acyl-CoA supply for lipid synthesis. Supporting Evidence: PMID:11477098 this strain had levels of in vivo beta-oxidation of exogenous oleate reduced 3-fold when compared with the isogenic parent |
| GO:0032787 monocarboxylic acid metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA for monocarboxylic acid metabolic process; too general. Proposed replacements: long-chain fatty acid metabolic process Supporting Evidence: PMID:7650027 Among C8-C18 saturated fatty acids, Faa4p and Faa1p both prefer C14:0 |
| GO:0035336 long-chain fatty-acyl-CoA metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for long-chain fatty-acyl-CoA metabolic process from the ACSL node; correct. Supporting Evidence: PMID:11477098 The faa1 Delta faa4 Delta strain had a marked reduction in endogenous acyl-CoA pools, suggesting these enzymes play a role in maintenance of endogenous acyl-CoA pools, metabolism and trafficking |
| GO:0035336 long-chain fatty-acyl-CoA metabolic process | IGI PMID:11477098 The Acyl-CoA synthetases encoded within FAA1 and FAA4 in Sac... | ACCEPT | Summary: IGI with FAA1 (Faergeman et al. 2001): faa1 faa4 cells have markedly reduced acyl-CoA pools. Supporting Evidence: PMID:11477098 The faa1 Delta faa4 Delta strain had a marked reduction in endogenous acyl-CoA pools, suggesting these enzymes play a role in maintenance of endogenous acyl-CoA pools, metabolism and trafficking |
| GO:0035336 long-chain fatty-acyl-CoA metabolic process | IMP PMID:11477098 The Acyl-CoA synthetases encoded within FAA1 and FAA4 in Sac... | ACCEPT | Summary: IMP (Faergeman et al. 2001): same study; Faa4p maintains acyl-CoA pools with Faa1p. Supporting Evidence: PMID:11477098 The faa1 Delta faa4 Delta strain had a marked reduction in endogenous acyl-CoA pools, suggesting these enzymes play a role in maintenance of endogenous acyl-CoA pools, metabolism and trafficking |
| GO:0044539 long-chain fatty acid import into cell | IGI PMID:12601005 Vectorial acylation in Saccharomyces cerevisiae. Fat1p and f... | ACCEPT | Summary: IGI with FAT1 and FAA1 (Zou et al. 2003): Faa4p is part of the Fat1p-Faa1p/Faa4p vectorial acylation complex; co-immunoprecipitation and suppressor genetics. Supporting Evidence: PMID:12601005 co-expressed, differentially tagged Fat1p and Faa1p or Faa4p were co-immunoprecipitated PMID:12601005 fatty acid import by vectorial acylation in yeast requires a multiprotein complex, which consists of Fat1p and Faa1p or Faa4p |
| GO:0044539 long-chain fatty acid import into cell | IGI PMID:12601005 Vectorial acylation in Saccharomyces cerevisiae. Fat1p and f... | ACCEPT | Summary: IGI with FAA1 (Zou et al. 2003): FAA4 on a multicopy plasmid suppresses the import defect of faa1 faa4 cells. Supporting Evidence: PMID:12601005 plasmids were identified encoding FAA1, FAT1, and FAA4 in the faa1Delta faa4Delta strain |
| GO:0044539 long-chain fatty acid import into cell | IGI PMID:27136724 Long-chain bases of sphingolipids are transported into cells... | ACCEPT | Summary: IGI with FAA1 (Narita et al. 2016): long-chain fatty acid transport is largely impaired in faa1 faa4 cells. Supporting Evidence: PMID:27136724 LCFA transports were largely impaired in faa1Ξ faa4Ξ cells |
| GO:1905329 sphingoid long-chain base transport | IGI PMID:27136724 Long-chain bases of sphingolipids are transported into cells... | KEEP AS NON CORE | Summary: IGI with FAA1 (Narita et al. 2016): long-chain base uptake is greatly reduced in faa1 faa4 cells; Faa4 has weak transport activity compared with Faa1, consistent with its limited plasma membrane pool. Supporting Evidence: PMID:27136724 We found that LCB uptake was greatly reduced in an ACS double deletion mutant (faa1Ξ faa4Ξ) PMID:27136724 The partial localization of Faa4 in the plasma membrane is consistent with the weak transport activity of Faa4 |
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Download this section (compressed HTML)Q: What signals drive Faa4p relocalisation from the ER to lipid droplets in stationary phase, and does lipid droplet association change its substrate specificity or channel acyl-CoA to triacylglycerol synthesis?
Experiment: Use an ER-retained versus LD-targeted Faa4p variant in a faa1 faa4 background and measure incorporation of labelled oleate into triacylglycerol versus phospholipids during the diauxic shift.
Hypothesis: Lipid droplet-localised Faa4p channels exogenous fatty acids into triacylglycerol in stationary phase.
Long chain fatty acyl-CoA synthetase; activates fatty acids with a preference for C12:0-C16:0 chain lengths; role in the competitive import of long-chain fatty acids and sphingoid long-chain bases; role in stationary phase survival; localizes to lipid particles and the plasma membrane; role in sphingolipid-to-glycerolipid metabolism; forms cytoplasmic foci upon replication stress; faa1 faa4 double null complemented by any of human ACSBG1, ACSL1, 3, 4, 5, 6, SLC27A2, or 4
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