FAA1 (YOR317W) encodes the major long-chain fatty acyl-CoA synthetase (ACSL family, EC 6.2.1.3) of Saccharomyces cerevisiae. It esterifies C12-C16 saturated (highest with myristate and pentadecanoate) and C14-C18 unsaturated fatty acids to their CoA thioesters in an ATP- and Mg2+-dependent reaction, providing the bulk of cellular oleoyl-CoA synthetase activity from exogenous fatty acids. Together with its paralog Faa4p, and in a complex with the FATP-family protein Fat1p, Faa1p couples uptake of exogenous long-chain fatty acids to their activation (vectorial acylation): faa1 faa4 double mutants are severely defective in long-chain fatty acid import, have depleted acyl-CoA pools and reduced oxidation of exogenous oleate. Faa1p also supplies myristoyl-CoA for protein N-myristoylation, activates hexadecenoic acid in the sphingolipid-to-glycerolipid (sphingosine 1-phosphate degradation) pathway, and is required with Faa4p for uptake of sphingoid long-chain bases. Faa1p is a peripheral membrane protein found at the plasma membrane, on lipid droplets and in the ER. Its acyl-CoA products feed phospholipid and neutral lipid synthesis and, via peroxisomal Pxa1/Pxa2 import, beta-oxidation.
| 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 the ACSL node PTN000645126 (yeast Faa1/Faa4, mammalian ACSL donors). Faa1p activates exogenous long-chain fatty acids for downstream metabolism. 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 | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for long-chain fatty acid-CoA ligase from the plant/animal/fungal ACSL node; Faa1p is the experimentally characterised yeast ACSL. Faa1p appearing among donors reflects its own experimental annotations. Supporting Evidence: PMID:8206942 In vitro assays of C3:0-C24:0 fatty acids indicate that Faa1p prefers C12:0-C16:0, with myristic and pentadecanoic acid (C15:0) having the highest activities |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IDA PMID:8206942 Biochemical studies of three Saccharomyces cerevisiae acyl-C... | ACCEPT | Summary: IDA (Knoll et al. 1994): His-tagged Faa1p purified from a fadD E. coli strain activated C12-C16 fatty acids, highest with myristate and pentadecanoate; palmitate, oleate and other long-chain substrates are also used (UniProt). Supporting Evidence: PMID:8206942 We have expressed Faa1p, Faa2p, and Faa3p in a strain of Escherichia coli that lacks its own endogenous acyl-CoA synthetase (FadD) PMID:8206942 In vitro assays of C3:0-C24:0 fatty acids indicate that Faa1p prefers C12:0-C16:0, with myristic and pentadecanoic acid (C15:0) having the highest activities |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA from Rhea/EC 6.2.1.3 mappings of UniProt catalytic activities; matches the experimentally determined activity. Supporting Evidence: file:yeast/FAA1/FAA1-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 FAA4 (Faergeman et al. 2001): oleoyl-CoA formed from exogenous oleate fell to <10% of wild type in faa1 and faa1 faa4 cells. 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 FAA4 (Nakahara et al. 2012): Faa1 and Faa4 are the acyl-CoA synthetases that 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): oleoyl-CoA levels from exogenous oleate fall below 10% of wild type in faa1 single mutants. 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 | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (YEAST-FAO-PWY) for the EC 6.2.1.3 activation step. The activity is correct for Faa1p; note that Faa1p acts at the plasma membrane/ER/lipid droplets on exogenous fatty acids, upstream of peroxisomal import of acyl-CoAs, rather than inside peroxisomes (the intraperoxisomal ligase is Faa2p). Supporting Evidence: PMID:8206942 In vitro assays of C3:0-C24:0 fatty acids indicate that Faa1p prefers C12:0-C16:0, with myristic and pentadecanoic acid (C15:0) having the highest activities PMID:11477098 this strain had levels of in vivo beta-oxidation of exogenous oleate reduced 3-fold when compared with the isogenic parent |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | KEEP AS NON CORE | Summary: HDA from the mitochondrial proteome of Sickmann et al. 2003. Faa1p has been repeatedly detected in purified mitochondria, but it has no known mitochondrial function and its established locations are the plasma membrane, lipid droplets and ER (membrane contact or co-purification cannot be excluded). Supporting Evidence: PMID:21820081 the long chain fatty acyl-CoA synthase Faa1p was found in LP [17], mitochondria [58] and the plasma membrane [59] |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | KEEP AS NON CORE | Summary: HDA from the PROMITO mitochondrial proteome (Reinders et al. 2006); same considerations as the other mitochondrial proteomics rows. Supporting Evidence: PMID:21820081 the long chain fatty acyl-CoA synthase Faa1p was found in LP [17], mitochondria [58] and the plasma membrane [59] |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | KEEP AS NON CORE | Summary: HDA from a quantitative mitochondrial proteome/phosphoproteome study (Renvoise et al. 2014); a proteomic detection without functional data. Supporting Evidence: PMID:21820081 the long chain fatty acyl-CoA synthase Faa1p was found in LP [17], mitochondria [58] and the plasma membrane [59] |
| GO:0005741 mitochondrial outer membrane | HDA PMID:16407407 Proteomic analysis of the yeast mitochondrial outer membrane... | KEEP AS NON CORE | Summary: HDA from the mitochondrial outer membrane proteome (Zahedi et al. 2006). Faa1p is a peripheral membrane protein that could associate with the outer membrane or contaminate the preparation; no function there is known. Supporting Evidence: PMID:21820081 the long chain fatty acyl-CoA synthase Faa1p was found in LP [17], mitochondria [58] and the plasma membrane [59] |
| GO:0005783 endoplasmic reticulum | HDA PMID:22842922 Dissecting DNA damage response pathways by analysing protein... | ACCEPT | Summary: HDA from a GFP-localisation screen (Tkach et al. 2012). Consistent with lipid droplet studies that see Faa1-GFP additionally in the ER. Supporting Evidence: PMID:24868093 Faa1-GFP appeared to be visible in additional cellular compartments, likely the ER |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: HDA from the SWAT-tag library localisation (Yofe et al. 2016); consistent with other evidence for ER association. Supporting Evidence: PMID:24868093 Faa1-GFP appeared to be visible in additional cellular compartments, likely the ER |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for ER (is_active_in) from the ACSL family node; consistent with yeast GFP data. Supporting Evidence: PMID:24868093 Faa1-GFP appeared to be visible in additional cellular compartments, likely the ER |
| 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 (Grillitsch et al. 2011), which lists Faa1p among lipid particle proteins. Supporting Evidence: PMID:21820081 the long chain fatty acyl-CoA synthase Faa1p was found in LP [17], mitochondria [58] and the plasma membrane [59] |
| GO:0005811 lipid droplet | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for lipid droplet from node PTN000645126 (yeast Faa1p/Faa4p and human ACSL donors); correct for Faa1p. 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): Faa1p identified as a major lipid particle protein. 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): high-confidence LD proteome plus microscopy confirming Faa1 on LDs. Supporting Evidence: PMID:24868093 We showed that two proteins (Faa1 and Hfd1), previously identified in yeast LD proteomes, in fact, do localize to 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/FAA1/FAA1-uniprot.txt SUBCELLULAR LOCATION: Lipid droplet |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways RCA (YEAST-FAO-PWY) placing the activation step in the cytosol. Faa1p acts on the cytoplasmic face of membranes (plasma membrane, ER, lipid droplets) rather than as a soluble cytosolic enzyme; the term is a default compartment of the pathway conversion, not an observation. Supporting Evidence: PMID:27136724 We found that Faa1-GFP was mainly localized in the plasma membrane 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:0005886 plasma membrane | HDA PMID:16622836 The plasma membrane proteome of Saccharomyces cerevisiae and... | ACCEPT | Summary: HDA from a plasma membrane proteome (Delom et al. 2006); consistent with GFP localisation at the plasma membrane. Supporting Evidence: PMID:27136724 We found that Faa1-GFP was mainly localized in the plasma membrane |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for plasma membrane from the fungal ACSL node (Faa1/Faa3/Faa4 donors); consistent with yeast data. Supporting Evidence: PMID:27136724 We found that Faa1-GFP was mainly localized in the plasma membrane |
| GO:0005886 plasma membrane | IDA PMID:27136724 Long-chain bases of sphingolipids are transported into cells... | ACCEPT | Summary: IDA (Narita et al. 2016): Faa1-GFP localised mainly to the plasma membrane, consistent with its role in uptake of fatty acids and long-chain bases. Supporting Evidence: PMID:27136724 We found that Faa1-GFP was mainly localized in the plasma membrane |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0039, cell membrane), based on Narita et al. 2016. Supporting Evidence: file:yeast/FAA1/FAA1-uniprot.txt Cell membrane {ECO:0000269|PubMed:27136724} |
| GO:0016405 CoA-ligase activity | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA for CoA-ligase activity. Correct but very general; Faa1p's activity is the long-chain fatty acid-CoA ligase. Proposed replacements: long-chain fatty acid-CoA ligase activity Supporting Evidence: PMID:8206942 In vitro assays of C3:0-C24:0 fatty acids indicate that Faa1p prefers C12:0-C16:0, with myristic and pentadecanoic acid (C15:0) having the highest activities |
| GO:0019395 fatty acid oxidation | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA for fatty acid oxidation. Faa1p supplies cytosolic acyl-CoA that is partly imported into peroxisomes via Pxa1/Pxa2, and faa1 faa4 cells oxidise exogenous oleate 3-fold less, so it contributes to fatty acid oxidation; but its main role is activation of imported fatty acids for lipid synthesis, and the peroxisomal ligase dedicated to beta-oxidation is Faa2p. 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:0031956 medium-chain fatty acid-CoA ligase activity | IDA PMID:8206942 Biochemical studies of three Saccharomyces cerevisiae acyl-C... | KEEP AS NON CORE | Summary: IDA (Knoll et al. 1994): Faa1p activates C12:0 (laurate), which GO classifies as medium-chain, in vitro. A real but minor activity; Faa2p is the physiological medium-chain ligase. Supporting Evidence: PMID:8206942 In vitro assays of C3:0-C24:0 fatty acids indicate that Faa1p prefers C12:0-C16:0, with myristic and pentadecanoic acid (C15:0) having the highest activities |
| GO:0031956 medium-chain fatty acid-CoA ligase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: IEA from Rhea (dodecanoate and related C12 reactions). Supported by in vitro data but secondary to the long-chain activity. Supporting Evidence: file:yeast/FAA1/FAA1-uniprot.txt Reaction=dodecanoate + ATP + CoA = dodecanoyl-CoA + AMP + diphosphate |
| GO:0032787 monocarboxylic acid metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA for monocarboxylic acid metabolic process. Too general; Faa1p acts in long-chain fatty acid metabolism. Proposed replacements: long-chain fatty acid metabolic process 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: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; Faa1p produces long-chain acyl-CoAs. 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 FAA4 (Faergeman et al. 2001): faa1 faa4 cells have markedly reduced endogenous 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): oleoyl-CoA formation from exogenous oleate is strongly reduced in faa1 cells. 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:0044539 long-chain fatty acid import into cell | IGI PMID:12601005 Vectorial acylation in Saccharomyces cerevisiae. Fat1p and f... | ACCEPT | Summary: IGI with FAT1 (Zou et al. 2003): faa1 fat1 cells are defective in long-chain fatty acid import and are rescued by FAA1 or FAT1; supports Faa1p as part of the vectorial acylation machinery. Supporting Evidence: PMID:12601005 plasmids were identified encoding FAA1, FAT1, and FAA4 in the faa1Delta faa4Delta strain and encoding FAA1 and FAT1 in the faa1Delta fat1Delta strain PMID:12601005 indicating Faa1p and Fat1p play distinct roles in the fatty acid import process |
| 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 FAA4 (Zou et al. 2003): suppressor analysis and co-immunoprecipitation indicate a Fat1p-Faa1p/Faa4p import complex. Supporting Evidence: 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 FAA4 (Zou et al. 2003): faa1 faa4 cells fail to accumulate C1-BODIPY-C12 and are rescued by FAA1, FAA4 or FAT1 on multicopy plasmids. Supporting Evidence: PMID:12601005 plasmids were identified encoding FAA1, FAT1, and FAA4 in the faa1Delta faa4Delta strain and encoding FAA1 and FAT1 in the faa1Delta fat1Delta 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 FAA4 (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:0044539 long-chain fatty acid import into cell | IMP PMID:12601005 Vectorial acylation in Saccharomyces cerevisiae. Fat1p and f... | ACCEPT | Summary: IMP (Zou et al. 2003): FAA1 deletion contributes to the import defect, with Faa1p and Fat1p playing distinct roles in import. Supporting Evidence: PMID:12601005 indicating Faa1p and Fat1p play distinct roles in the fatty acid import process |
| GO:0044539 long-chain fatty acid import into cell | IMP PMID:27136724 Long-chain bases of sphingolipids are transported into cells... | ACCEPT | Summary: IMP (Narita et al. 2016): Faa1 acts in long-chain fatty acid uptake at the plasma membrane. Supporting Evidence: PMID:27136724 These results suggest that Faa1 and Faa4 act as transporters both for LCFAs and LCBs |
| GO:1905329 sphingoid long-chain base transport | IGI PMID:27136724 Long-chain bases of sphingolipids are transported into cells... | ACCEPT | Summary: IGI with FAA4 (Narita et al. 2016): long-chain base uptake is greatly reduced in faa1 faa4 cells and, unlike LCFA uptake, does not need ATP, suggesting a direct transport role. Supporting Evidence: PMID:27136724 We found that LCB uptake was greatly reduced in an ACS double deletion mutant (faa1Ξ faa4Ξ) PMID:27136724 These results suggest that Faa1 and Faa4 act as transporters both for LCFAs and LCBs |
| GO:1905329 sphingoid long-chain base transport | IMP PMID:27136724 Long-chain bases of sphingolipids are transported into cells... | ACCEPT | Summary: IMP (Narita et al. 2016): Faa1 is the major contributor to long-chain base uptake; a non-canonical function of this acyl-CoA synthetase. Supporting Evidence: PMID:27136724 These results suggest that Faa1 and Faa4 act as transporters both for LCFAs and LCBs |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: How does Faa1p mediate ATP-independent uptake of sphingoid long-chain bases, which are not substrates of its ligase activity? Is there a transport path through the protein or via its partner Fat1p?
Q: Should the YeastPathways fatty acid oxidation pathway attach the cytosolic/plasma-membrane ACSLs (Faa1p, Faa4p) as upstream suppliers of acyl-CoA for Pxa1/Pxa2 import, distinct from the intraperoxisomal ligases (Faa2p, Fat1p)?
Experiment: Reconstitute purified Faa1p in proteoliposomes and measure ATP-independent transfer of labelled dihydrosphingosine across the bilayer, with catalytically dead FACS-motif mutants as controls.
Hypothesis: Faa1p directly translocates sphingoid long-chain bases across the plasma membrane.
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; accounts for most acyl-CoA synthetase activity; localizes to lipid particles and the plasma membrane; role in sphingolipid-to-glycerolipid metabolism; forms ER foci upon replication stress; faa1 faa4 double null complemented by any of human ACSBG1, ACSL1, 3, 4, 5, 6, SLC27A2, or 4
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)