FAT1 (YBR041W) encodes the yeast member of the fatty acid transport protein (FATP/SLC27) family, a dual-function membrane protein with very long-chain acyl-CoA synthetase activity (VLCS) and a separable role in uptake of exogenous long-chain fatty acids. Fat1p provides most cellular C24-acyl-CoA synthetase activity, and fat1 deletion strains accumulate C22-C26 very long-chain fatty acids in phospholipids and sphingolipids. In peroxisomes Fat1p (with Faa2p) re-esterifies very long-chain fatty acids released by the Pxa1p/Pxa2p ABC transporter on the matrix side of the peroxisomal membrane, enabling their beta-oxidation. At the plasma membrane Fat1p has an N(in)-C(in) topology with its catalytic motifs facing the cytosol and forms a complex with the long-chain acyl-CoA synthetases Faa1p or Faa4p that couples fatty acid import to activation (vectorial acylation); fat1 mutants are impaired in long-chain fatty acid uptake and grow poorly under hypoxia or when fatty acid synthesis is blocked. Fat1p is also found on lipid droplets and in the ER. Loss of Fat1p alters membrane saturation and secondarily impairs ER protein quality control.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000038 very long-chain fatty acid metabolic process | IMP PMID:9660783 Disruption of the Saccharomyces cerevisiae FAT1 gene decreas... | ACCEPT | Summary: IMP (Watkins et al. 1998): fat1 deletion strains accumulate C22-C26 fatty acids and have reduced VLCS activity, restored by FAT1. Supporting Evidence: PMID:9660783 FAT1 deletion strains grown on either dextrose or oleic acid medium accumulated very long-chain fatty acids PMID:9660783 These studies suggest that the FAT1 gene product has VLCS activity that is essential for normal cellular very long-chain fatty acid homeostasis |
| GO:0000038 very long-chain fatty acid metabolic process | IMP PMID:9988704 The Saccharomyces cerevisiae FAT1 gene encodes an acyl-CoA s... | ACCEPT | Summary: IMP (Choi and Martin 1999): disruption of FAT1 causes accumulation of VLCFAs in sphingolipid and phospholipid fractions. Supporting Evidence: PMID:9988704 Disruption of the FAT1 gene results in the accumulation of very long chain fatty acids in the sphingolipid and phospholipid fractions |
| GO:0000329 fungal-type vacuole membrane | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | KEEP AS NON CORE | Summary: HDA from the SWAT-tag localisation library (Yofe et al. 2016). A single high-throughput observation; Fat1p's established locations are plasma membrane, peroxisome, ER and lipid droplets, and no vacuolar function is known (possibly turnover or tag effects). |
| GO:0001676 long-chain fatty acid metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA for long-chain fatty acid metabolic process from the FATP node PTN001945407 (mammalian SLC27 donors). Fat1p is required for long-chain fatty acid import and its loss lowers oleoyl-CoA from exogenous oleate, but its own ligase activity is VLCFA-directed; involvement in LCFA metabolism is mainly via import. Supporting Evidence: PMID:10880966 have a greatly diminished capacity to transport exogenous long-chain fatty acids, and have very long-chain acyl CoA synthetase activities that were 40% wild-type PMID:10880966 octanoate, a medium-chain fatty acid was transported in a Fat1p- and FATP-independent manner while the long-chain fatty acids myristate, palmitate, and oleate required either Fat1p or FATP for maximal levels of transport |
| GO:0004467 long-chain fatty acid-CoA ligase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA for long-chain fatty acid-CoA ligase from the FATP node (mammalian FATP1/2/4 donors). FAT1 disruption does not reduce long-chain acyl-CoA synthetase activity, but overexpressed Fat1p contributes oleoyl-CoA synthetase activity, so the activity exists but is minor compared with its VLCS activity. Supporting Evidence: PMID:11330068 Disruption of this gene decreased VLCS activity, but had no effect on long-chain acyl-CoA synthetase activity PMID:12601005 When expressed from a 2-mu plasmid, Fat1p contributes significant oleoyl-CoA synthetase activity |
| GO:0004467 long-chain fatty acid-CoA ligase activity | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways RCA (YEAST-FAO-PWY) assigning Fat1p to the long-chain (EC 6.2.1.3) activation step. In the oxidation pathway Fat1p re-activates very long-chain fatty acids inside peroxisomes; the appropriate activity is very long-chain fatty acid-CoA ligase. Proposed replacements: very long-chain fatty acid-CoA ligase activity Supporting Evidence: PMID:22493507 The Pxa1p-Pxa2p complex functionally interacts with the acyl-CoA synthetases Faa2p and/or Fat1p on the inner surface of the peroxisomal membrane for subsequent re-esterification of the VLCFAs PMID:9988704 Fat1p accounts for approximately 90% of the C24-specific acyl-CoA synthetase activity in glucose-grown cells |
| GO:0005324 long-chain fatty acid transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for long-chain fatty acid transmembrane transporter activity from the FATP node (yeast Fat1p and mammalian FATP donors). Fat1p is required for long-chain fatty acid uptake through a function separable from its VLCS activity; whether it translocates fatty acids itself or acts by vectorial acylation with Faa1p/Faa4p is still debated, but this is the established GO representation of FATP import function. Supporting Evidence: PMID:9079682 These data support the hypothesis that Fat1p is involved in long-chain fatty acid uptake and may represent a long-chain fatty acid transport protein PMID:12601005 fatty acid import by vectorial acylation in yeast requires a multiprotein complex, which consists of Fat1p and Faa1p or Faa4p |
| GO:0005324 long-chain fatty acid transmembrane transporter activity | IMP PMID:9079682 Disruption of the Saccharomyces cerevisiae homologue to the ... | ACCEPT | Summary: IMP (Faergeman et al. 1997): fat1 disruption reduces BODIPY-fatty acid uptake and oleate uptake 2-3 fold. Later work showed the import function is separable from acyl-CoA synthetase activity, supporting a transport role, although direct translocation has not been reconstituted. Supporting Evidence: PMID:9079682 a marked decrease in the uptake of the fluorescent long-chain fatty acid analogue boron dipyrromethene difluoride dodecanoic acid (BODIPY-3823) PMID:9079682 These data support the hypothesis that Fat1p is involved in long-chain fatty acid uptake and may represent a long-chain fatty acid transport protein |
| GO:0005777 peroxisome | EXP PMID:11330068 Disruption of a yeast very-long-chain acyl-CoA synthetase ge... | ACCEPT | Summary: EXP (Watkins et al. 2001): fractionation shows FAT1-dependent VLCS activity in peroxisomes but not mitochondria. Supporting Evidence: PMID:11330068 revealed that VLCS activity was peroxisomal and not mitochondrial |
| GO:0005777 peroxisome | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for peroxisome from node PTN001186290, seeded by yeast Fat1p; reflects Fat1p's own experimental localisation. Supporting Evidence: PMID:11330068 revealed that VLCS activity was peroxisomal and not mitochondrial |
| GO:0005777 peroxisome | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0204); consistent with experimental data. Supporting Evidence: file:yeast/FAT1/FAT1-uniprot.txt Peroxisome membrane {ECO:0000269|PubMed:22493507}; Multi-pass membrane protein |
| GO:0005777 peroxisome | IMP PMID:9660783 Disruption of the Saccharomyces cerevisiae FAT1 gene decreas... | ACCEPT | Summary: IMP (Watkins et al. 1998): VLCS activity associated with peroxisomes (and microsomes) is reduced in fat1 deletion strains. Supporting Evidence: PMID:9660783 revealed that VLCS activity was associated with peroxisomes and microsomes but not mitochondria PMID:9660783 Disruption of this gene decreased, but did not abolish, cellular VLCS activity |
| GO:0005778 peroxisomal membrane | EXP PMID:22493507 Peroxisomal fatty acid uptake mechanism in Saccharomyces cer... | ACCEPT | Summary: EXP (van Roermund et al. 2012): Fat1p (and/or Faa2p) acts on the inner surface of the peroxisomal membrane with Pxa1p/Pxa2p. Supporting Evidence: PMID:22493507 The Pxa1p-Pxa2p complex functionally interacts with the acyl-CoA synthetases Faa2p and/or Fat1p on the inner surface of the peroxisomal membrane for subsequent re-esterification of the VLCFAs |
| GO:0005778 peroxisomal membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0203, peroxisome membrane); consistent with experimental data. Supporting Evidence: file:yeast/FAT1/FAT1-uniprot.txt Peroxisome membrane {ECO:0000269|PubMed:22493507}; Multi-pass membrane protein |
| GO:0005783 endoplasmic reticulum | IDA PMID:9988704 The Saccharomyces cerevisiae FAT1 gene encodes an acyl-CoA s... | ACCEPT | Summary: IDA (Choi and Martin 1999): GFP fusions and fractionation place most Fat1p in internal membranes; microsomal VLCS activity is also FAT1-dependent. Supporting Evidence: PMID:9988704 indicate that the majority of Fat1p is located in internal cellular locations PMID:9660783 revealed that VLCS activity was associated with peroxisomes and microsomes but not mitochondria |
| 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/FAT1/FAT1-uniprot.txt SUBCELLULAR LOCATION: Lipid droplet |
| GO:0005811 lipid droplet | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for lipid droplet from node PTN001186290 seeded by yeast Fat1p; reflects experimental data. 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): Fat1p identified as a 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): Fat1 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 | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0154); consistent with experimental data. Supporting Evidence: file:yeast/FAT1/FAT1-uniprot.txt SUBCELLULAR LOCATION: Lipid droplet |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA (YEAST-FAO-PWY) default cytosol location. Fat1p is a multi-pass integral membrane protein (plasma membrane, peroxisomal membrane, ER, lipid droplets); it is not cytosolic. Supporting Evidence: file:yeast/FAT1/FAT1-uniprot.txt Cell membrane {ECO:0000269|PubMed:17679730}; Multi-pass membrane protein file:yeast/FAT1/FAT1-uniprot.txt Peroxisome membrane {ECO:0000269|PubMed:22493507}; Multi-pass membrane protein |
| GO:0005886 plasma membrane | EXP PMID:17679730 Topology of the yeast fatty acid transport protein Fat1p: me... | ACCEPT | Summary: EXP (Obermeyer et al. 2007): epitope-tagged Fat1p localises to the plasma membrane with an N(in)-C(in) topology. Supporting Evidence: PMID:17679730 Plasma membrane localization of the tagged proteins was assessed by immunofluorescence PMID:17679730 The N(in)-C(in) topology results in the placement of the ATP/AMP and FATP/VLACS domains of Fat1p on the inner face of the plasma membrane |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for plasma membrane from the FATP node (mammalian FATP donors); consistent with yeast data. Supporting Evidence: PMID:17679730 The N(in)-C(in) topology results in the placement of the ATP/AMP and FATP/VLACS domains of Fat1p on the inner face of the plasma membrane |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0039, cell membrane); consistent with experimental data. Supporting Evidence: file:yeast/FAT1/FAT1-uniprot.txt Cell membrane {ECO:0000269|PubMed:17679730}; Multi-pass membrane protein |
| GO:0006515 protein quality control | IMP PMID:31746669 Dysregulation of very-long-chain fatty acid metabolism cause... | MARK AS OVER ANNOTATED | Summary: IMP (Micoogullari et al. 2020): fat1 mutants show ER protein quality control defects with UPR induction, explained by altered membrane lipid saturation and impaired Ole1 function. Fat1p does none of the work of protein quality control; this is an indirect consequence of disturbed VLCFA metabolism. Supporting Evidence: PMID:31746669 We find that this mutant shows significant defects in ER protein quality control with compensatory induction of the UPR PMID:31746669 Our data support the latter, as loss of Fat1 compromised the function of Ole1, the sole fatty acid desaturase in yeast |
| GO:0006631 fatty acid metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA for fatty acid metabolic process; correct but general. Fat1p's specific metabolic role is in very long-chain fatty acid metabolism. Proposed replacements: very long-chain fatty acid metabolic process Supporting Evidence: PMID:9988704 Disruption of the FAT1 gene results in the accumulation of very long chain fatty acids in the sphingolipid and phospholipid fractions |
| GO:0009898 cytoplasmic side of plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for cytoplasmic side of plasma membrane from node PTN001186290 seeded by yeast Fat1p; reflects the experimental topology. Supporting Evidence: PMID:17679730 The N(in)-C(in) topology results in the placement of the ATP/AMP and FATP/VLACS domains of Fat1p on the inner face of the plasma membrane |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:17679730 Topology of the yeast fatty acid transport protein Fat1p: me... | ACCEPT | Summary: IDA (Obermeyer et al. 2007): the ATP/AMP and FATP/VLACS motifs and the Faa1p-binding C-terminus face the cytoplasmic side of the plasma membrane. Supporting Evidence: PMID:17679730 The N(in)-C(in) topology results in the placement of the ATP/AMP and FATP/VLACS domains of Fat1p on the inner face of the plasma membrane |
| GO:0019395 fatty acid oxidation | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA for fatty acid oxidation. Fat1p re-activates VLCFAs inside peroxisomes for beta-oxidation and is proposed to limit VLCFA levels by facilitating their beta-oxidation; a genuine but secondary role relative to VLCFA homeostasis and fatty acid uptake. Supporting Evidence: PMID:22493507 The Pxa1p-Pxa2p complex functionally interacts with the acyl-CoA synthetases Faa2p and/or Fat1p on the inner surface of the peroxisomal membrane for subsequent re-esterification of the VLCFAs PMID:9988704 apparently by facilitating beta-oxidation of excess intermediate length (C20-C24) species |
| GO:0031957 very long-chain fatty acid-CoA ligase activity | EXP PMID:15699031 Comparative biochemical studies of the murine fatty acid tra... | ACCEPT | Summary: EXP (DiRusso et al. 2005): Fat1p's very long-chain fatty acid activation is an intrinsic activity separable from its fatty acid import function. Supporting Evidence: PMID:15699031 is required for both the import of long-chain fatty acids and the activation of very long-chain fatty acids; these activities intrinsic to Fat1p are separable functions |
| GO:0031957 very long-chain fatty acid-CoA ligase activity | IMP PMID:9660783 Disruption of the Saccharomyces cerevisiae FAT1 gene decreas... | ACCEPT | Summary: IMP (Watkins et al. 1998): fat1 deletion reduces cellular VLCS activity, restored by FAT1 expression in proportion to expression level. Supporting Evidence: PMID:9660783 Disruption of this gene decreased, but did not abolish, cellular VLCS activity PMID:9660783 These studies suggest that the FAT1 gene product has VLCS activity that is essential for normal cellular very long-chain fatty acid homeostasis |
| GO:0044539 long-chain fatty acid import into cell | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for long-chain fatty acid import into cell from the FATP node; Fat1p is experimentally required for long-chain fatty acid uptake in yeast. Supporting Evidence: PMID:10880966 have a greatly diminished capacity to transport exogenous long-chain fatty acids, and have very long-chain acyl CoA synthetase activities that were 40% wild-type PMID:15699031 is required for both the import of long-chain fatty acids and the activation of very long-chain fatty acids; these activities intrinsic to Fat1p are separable functions |
| 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 and FAA4 (Zou et al. 2003): Fat1p acts with Faa1p or Faa4p in a vectorial acylation complex for fatty acid import. 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): multicopy FAA4 cannot replace Fat1p in faa1 fat1 cells, showing Fat1p has essential import functions. Supporting Evidence: PMID:12601005 Multicopy FAA4 could not suppress the growth defect in the faa1Delta fat1Delta strain indicating some essential functions of Fat1p cannot be performed by Faa4p |
| GO:0044539 long-chain fatty acid import into cell | IMP PMID:10880966 Murine FATP alleviates growth and biochemical deficiencies o... | ACCEPT | Summary: IMP (DiRusso et al. 2000): fat1 cells have greatly diminished long-chain fatty acid transport, restored by Fat1p or murine FATP; octanoate uptake is Fat1p-independent. Supporting Evidence: PMID:10880966 have a greatly diminished capacity to transport exogenous long-chain fatty acids, and have very long-chain acyl CoA synthetase activities that were 40% wild-type PMID:10880966 octanoate, a medium-chain fatty acid was transported in a Fat1p- and FATP-independent manner while the long-chain fatty acids myristate, palmitate, and oleate required either Fat1p or FATP for maximal levels of transport |
| 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 fat1 cells fail to accumulate C1-BODIPY-C12 and cannot grow when exogenous long-chain fatty acids are required. 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:0071944 cell periphery | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: HDA from the SWAT-tag library (Yofe et al. 2016); cell periphery is consistent with Fat1p's plasma membrane location. Supporting Evidence: file:yeast/FAT1/FAT1-uniprot.txt Cell membrane {ECO:0000269|PubMed:17679730}; Multi-pass membrane protein |
| GO:0120515 fatty acid-CoA ligase activity | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA for fatty acid-CoA ligase; correct but general. The characteristic activity is very long-chain fatty acid-CoA ligase. Proposed replacements: very long-chain fatty acid-CoA ligase activity Supporting Evidence: file:yeast/FAT1/FAT1-uniprot.txt Reaction=tetracosanoate + ATP + CoA = tetracosanoyl-CoA + AMP + PMID:9988704 Fat1p accounts for approximately 90% of the C24-specific acyl-CoA synthetase activity in glucose-grown cells |
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Download this section (compressed HTML)Q: Does Fat1p directly translocate long-chain fatty acids across the plasma membrane, or does it promote uptake only by metabolic trapping together with Faa1p/Faa4p?
Q: How is Fat1p distributed between plasma membrane, ER, lipid droplets and peroxisomal membrane, and what targets it to each compartment?
Experiment: Reconstitute purified wild-type and ligase-dead (ATP/AMP motif) Fat1p in proteoliposomes and measure flip-flop/translocation of fluorescent long-chain fatty acids with and without ATP/CoA.
Hypothesis: Fat1p mediates fatty acid translocation independently of acyl-CoA synthesis.
Very long chain fatty acyl-CoA synthetase and fatty acid transporter; activates imported fatty acids with a preference for very long lengths (C20-C26); has a separate function in the transport of long chain fatty acids
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