FAA3

UniProt ID: P39002
Organism: Saccharomyces cerevisiae S288C
Review Status: COMPLETE
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Gene Description

FAA3 (YIL009W) encodes a long-chain fatty acyl-CoA synthetase (ATP-dependent AMP-binding enzyme family, EC 6.2.1.3) of Saccharomyces cerevisiae. Purified Faa3p prefers C16 and C18 fatty acids with a cis-double bond at C9-C10 (palmitoleate, oleate), and its activity toward saturated substrates such as myristate is about two orders of magnitude lower than that of Faa1p or Faa2p. GFP-tagged Faa3p localises to the cell periphery/plasma membrane, and Faa3p has been reported to interact with the protein kinase Frk1p. Unlike Faa1p and Faa4p, Faa3p has no demonstrated major role in uptake of exogenous fatty acids, and no specific role in peroxisomal beta-oxidation; its physiological function remains poorly defined.

Existing Annotations Review

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 fungal/animal ACSL node PTN000645126. Faa3p activates C16/C18 unsaturated fatty acids in vitro.
Supporting Evidence:
PMID:8206942
Faa3p has a preference for C16 and C18 fatty acids with a cis-double bond at C-9-C-10
GO:0001676 long-chain fatty acid metabolic process
IGI
PMID:7962057
Saccharomyces cerevisiae contains four fatty acid activation... 		ACCEPT
Summary: IGI with FAA4 (Johnson et al. 1994), from the genetic analysis of the four FAA genes in long-chain fatty acid utilisation. Deferring to the curator; consistent with Faa3p's long-chain ligase activity.
Supporting Evidence:
PMID:7962057
We have recently isolated three unlinked Fatty Acid Activation (FAA) genes encoding long chain acylCoA synthetases and have now recovered a fourth by genetic complementation
GO:0001676 long-chain fatty acid metabolic process
IGI
PMID:7962057
Saccharomyces cerevisiae contains four fatty acid activation... 		ACCEPT
Summary: IGI with FAA1 (Johnson et al. 1994); same genetic study and rationale as the FAA4 IGI row.
Supporting Evidence:
PMID:7962057
We have recently isolated three unlinked Fatty Acid Activation (FAA) genes encoding long chain acylCoA synthetases and have now recovered a fourth by genetic complementation
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 the biochemical data on Faa3p.
Supporting Evidence:
PMID:8206942
Faa3p has a preference for C16 and C18 fatty acids with a cis-double bond at C-9-C-10
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): purified His-tagged Faa3p is an acyl-CoA synthetase preferring C16/C18 cis-9 unsaturated fatty acids.
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
Faa3p has a preference for C16 and C18 fatty acids with a cis-double bond at C-9-C-10
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 the experimentally determined long-chain activity.
Supporting Evidence:
file:yeast/FAA3/FAA3-uniprot.txt
Reaction=a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-
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. The activity is correct, but YeastCyc attaches all Faa paralogs to the beta-oxidation activation step; Faa3p has no specific evidence for supplying beta-oxidation (see fatty acid oxidation row).
Supporting Evidence:
PMID:8206942
Faa3p has a preference for C16 and C18 fatty acids with a cis-double bond at C-9-C-10
GO:0005783 endoplasmic reticulum
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: IBA for ER (is_active_in) from the broad ACSL node seeded by ER ACSLs of plants, flies and mammals. No yeast data place Faa3p in the ER (GFP shows plasma membrane), but no data exclude it either.
Supporting Evidence:
file:yeast/FAA3/FAA3-uniprot.txt
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14562095}
GO:0005811 lipid droplet
IBA
GO_REF:0000033 		MARK AS OVER ANNOTATED
Summary: IBA for lipid droplet from node PTN000645126, driven by Faa1p/Faa4p and human ACSL donors. Faa3p was not found in yeast lipid droplet proteomes, which recover Faa1p, Faa4p and Fat1p; the location does not appear to hold for Faa3p.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: COMPARTMENT OR COMPLEX MISMATCH
Supporting Evidence:
file:yeast/FAA3/FAA3-uniprot.txt
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14562095}
GO:0005829 cytosol
RCA
GO_REF:0000123 		MARK AS OVER ANNOTATED
Summary: YeastPathways RCA (YEAST-FAO-PWY) default cytosol compartment for the activation step. Faa3p is observed at the plasma membrane, not as a soluble cytosolic enzyme, and its role in fatty acid oxidation is unestablished.
Supporting Evidence:
file:yeast/FAA3/FAA3-uniprot.txt
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14562095}
GO:0005886 plasma membrane
EXP
PMID:14562095
Global analysis of protein localization in budding yeast. 		ACCEPT
Summary: EXP (Huh et al. 2003 GFP localisation): Faa3p-GFP at the cell periphery/plasma membrane.
Supporting Evidence:
PMID:14562095
expressing full-length, chromosomally tagged green fluorescent protein fusion proteins
file:yeast/FAA3/FAA3-uniprot.txt
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14562095}
GO:0005886 plasma membrane
IBA
GO_REF:0000033 		ACCEPT
Summary: IBA for plasma membrane from the fungal ACSL node; consistent with the GFP data for Faa3p.
Supporting Evidence:
file:yeast/FAA3/FAA3-uniprot.txt
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14562095}
GO:0005886 plasma membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: IEA from UniProt subcellular location (SL-0039, cell membrane), based on Huh et al. 2003.
Supporting Evidence:
file:yeast/FAA3/FAA3-uniprot.txt
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14562095}
GO:0016405 CoA-ligase activity
IEA
GO_REF:0000117 		MODIFY
Summary: ARBA IEA for CoA-ligase activity; correct but too general. The specific activity is long-chain fatty acid-CoA ligase.
Supporting Evidence:
PMID:8206942
Faa3p has a preference for C16 and C18 fatty acids with a cis-double bond at C-9-C-10
GO:0019395 fatty acid oxidation
RCA
GO_REF:0000123 		MARK AS OVER ANNOTATED
Summary: YeastPathways RCA for fatty acid oxidation. YeastCyc attaches every Faa paralog to the activation step of the oxidation pathway; there is no direct evidence that Faa3p supplies beta-oxidation (Johnson et al. found that no single FAA gene is responsible for routing imported fatty acids to beta-oxidation), and its low activity and plasma membrane location argue against a significant role.
Supporting Evidence:
PMID:7962057
None of the four known FAAs is exclusively responsible for targeting imported fatty acids to peroxisomal beta-oxidation pathways
PMID:8206942
The myristoyl-CoA synthetase activities of Faa1p and Faa2p are 2 orders of magnitude greater than that of Faa3p in vitro
GO:0031957 very long-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), which assayed C3:0-C24:0 substrates. The abstract reports a preference for C16/C18 cis-9 acids; activity on >C22 substrates is presumably reported in the full text, so this is kept as a minor, non-core activity deferring to the curator.
Supporting Evidence:
PMID:8206942
In vitro assays of C3:0-C24:0 fatty acids indicate that Faa1p prefers C12:0-C16:0
PMID:8206942
Faa3p has a preference for C16 and C18 fatty acids with a cis-double bond at C-9-C-10
GO:0032787 monocarboxylic acid metabolic process
IEA
GO_REF:0000117 		MODIFY
Summary: ARBA IEA for monocarboxylic acid metabolic process; too general. Long-chain fatty acid metabolic process is the appropriate term.
Supporting Evidence:
PMID:8206942
Faa3p has a preference for C16 and C18 fatty acids with a cis-double bond at C-9-C-10
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; Faa3p produces long-chain acyl-CoAs.
Supporting Evidence:
PMID:8206942
Faa3p has a preference for C16 and C18 fatty acids with a cis-double bond at C-9-C-10

Core Functions

Long-chain fatty acid-CoA ligase with a preference for C16/C18 cis-9 monounsaturated fatty acids; low-activity paralog of Faa1p located at the plasma membrane, physiological role not well defined.

Molecular Function:
long-chain fatty acid-CoA ligase activity
Directly Involved In:
long-chain fatty acid metabolic process
Cellular Locations:
plasma membrane
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
    Faa3p has a preference for C16 and C18 fatty acids with a cis-double bond at C-9-C-10
  • file:yeast/FAA3/FAA3-uniprot.txt
    SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14562095}

References

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Suggested Questions for Experts

Q: What is the in vivo role of Faa3p, given its low activity relative to Faa1p/Faa4p? Does it act on a specific pool (e.g. unsaturated fatty acids at the plasma membrane) or under specific conditions (hypoxia, sporulation)?

Q: Does YeastPathways have any yeast evidence for attaching Faa3p to the fatty acid oxidation pathway?

Suggested Experiments

Experiment: Measure oleate and palmitoleate uptake and oleoyl-CoA formation in faa1 faa4 versus faa1 faa3 faa4 strains under cerulenin or hypoxic conditions, and overexpress FAA3 in faa1 faa4 to test rescue.

Hypothesis: Faa3p contributes to activation of exogenous unsaturated fatty acids when Faa1p and Faa4p are absent.

Deep Research

SGD

(FAA3-deep-research-sgd.md)
SGD gene description for FAA3 (yeast) SGD

SGD gene description for FAA3 (yeast)

Long chain fatty acyl-CoA synthetase; activates imported fatty acids with a preference for C16:0-C18:0 chain lengths; green fluorescent protein (GFP)-fusion protein localizes to the cell periphery

📚 Additional Documentation

Notes

(FAA3-notes.md)

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