FAA4/YMR246W Summary Help

Standard Name FAA4
Systematic Name YMR246W
Feature Type ORF, Verified
Description Long chain fatty acyl-CoA synthetase; activates imported fatty acids with a preference for C12:0-C16:0 chain lengths; functions in long chain fatty acid import; important for survival during stationary phase; localized to lipid particles; involved in sphingolipid-to-glycerolipid metabolism; forms cytoplasmic foci upon DNA replication stress; FAA4 has a paralog, FAA1, that arose from the whole genome duplication (1, 2, 3, 4, 5, 6, 7 and see Summary Paragraph)
Name Description Fatty Acid Activation
Chromosomal Location
ChrXIII:759807 to 761891 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All FAA4 GO evidence and references
  View Computational GO annotations for FAA4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 2 genes
Resources
Pathways
Classical genetics
null
Large-scale survey
null
overexpression
Resources
82 total interaction(s) for 63 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 48
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 2
  • Co-fractionation: 1
  • PCA: 3

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 2
  • Negative Genetic: 8
  • Phenotypic Enhancement: 3
  • Positive Genetic: 3
  • Synthetic Growth Defect: 5
  • Synthetic Lethality: 3

Resources
Expression Summary
histogram
Resources
Length (a.a.) 694
Molecular Weight (Da) 77,267
Isoelectric Point (pI) 6.52
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIII:759807 to 761891 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2085 759807..761891 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004860
SUMMARY PARAGRAPH for FAA4

In order for yeast to utilize fatty acids, either as an energy source (via beta-oxidation) or for essential processes such as phospholipid biosynthesis and protein myristoylation, the fatty acids must first be converted into activated intermediates, acyl-CoAs, through thioesterification of fatty acids with coenzyme A. When fatty acids are synthesized de novo, activation is part of the process of synthesis and is accomplished by the same fatty acid synthetase complex (Fas1p-Fas2p) that initiates and elongates the fatty acid chain. However, yeast cells can also utilize exogenous, imported fatty acids, an ability that becomes essential if the fatty acid synthetase complex is inactivated by mutation or specific inhibitors such as cerulenin. These exogenous fatty acids are activated by one of five characterized yeast acyl-CoA synthetases: Faa1p, Faa2p, Faa3p, Faa4p, or Fat1p (see 8 and 9 for review).

FAA1 and FAA4 encode acyl-CoA synthetases with similar specificities and biological roles (10, 1). Both enzymes can activate fatty acids of a wide range of sizes, but have preferences for long chain lengths (C12:0-C16:0) (11, 12). Faa1p accounts for the majority of the detectable acyl-CoA synthetase activity during exponential growth (10) and FAA1 is expressed at much higher levels than all other FAA genes, under all conditions tested (3). Nevertheless, although faa1 deletion mutants have slight growth abnormalities, these cells still clearly import, activate and beta-oxidize exogenous fatty acids (10). faa1faa4 double mutant cells, however, are inviable in media containing cerulenin, and this phenotype can be completely rescued by overexpression of either FAA1 or FAA4, but not of FAA2 or FAA3 (1).

faa1faa4 double deletion mutants also have severe defects in the import of long chain fatty acids, indicating that these genes play some role in transport as well (13, 4). Overexpression of FAT1 can rescue the faa1faa4 import phenotype and there is evidence of physical interaction between Fat1p and Faa1p and/or Faa4p (4). Fat1p, Faa1p and Faa4p are hypothesized to couple import and activation of exogenous fatty acids by a process called vectorial acylation, wherein fatty acids are metabolically trapped as CoA thioesters upon transport (reviewed in 9). This process is thought to require Fat1p along with either Faa1p and/or Faa4p (4).

FAA4, unlike FAA1, is specifically induced during the diauxic/early post-diauxic transition and may be particularly important under starvation conditions. Higher levels of Faa4p help produce the activated fatty acids necessary for creating N-myristoylproteins, which are thought to play crucial roles in cell survival during stationary phase (3).

Last updated: 2010-02-11 Contact SGD

References cited on this page View Complete Literature Guide for FAA4
1) Johnson DR, et al.  (1994) Saccharomyces cerevisiae contains four fatty acid activation (FAA) genes: an assessment of their role in regulating protein N-myristoylation and cellular lipid metabolism. J Cell Biol 127(3):751-62
2) Athenstaedt K, et al.  (1999) Identification and characterization of major lipid particle proteins of the yeast Saccharomyces cerevisiae. J Bacteriol 181(20):6441-8
3) Ashrafi K, et al.  (1998) A role for Saccharomyces cerevisiae fatty acid activation protein 4 in regulating protein N-myristoylation during entry into stationary phase. J Biol Chem 273(40):25864-74
4) Zou Z, et al.  (2003) Vectorial acylation in Saccharomyces cerevisiae. Fat1p and fatty acyl-CoA synthetase are interacting components of a fatty acid import complex. J Biol Chem 278(18):16414-22
5) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
6) Nakahara K, et al.  (2012) The sjogren-larsson syndrome gene encodes a hexadecenal dehydrogenase of the sphingosine 1-phosphate degradation pathway. Mol Cell 46(4):461-71
7) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
8) Hettema EH and Tabak HF  (2000) Transport of fatty acids and metabolites across the peroxisomal membrane. Biochim Biophys Acta 1486(1):18-27
9) Black PN and Dirusso CC  (2007) Yeast acyl-CoA synthetases at the crossroads of fatty acid metabolism and regulation. Biochim Biophys Acta 1771(3):286-98
10) Duronio RJ, et al.  (1992) Isolation of a Saccharomyces cerevisiae long chain fatty acyl:CoA synthetase gene (FAA1) and assessment of its role in protein N-myristoylation. J Cell Biol 117(3):515-29
11) Knoll LJ, et al.  (1994) Biochemical studies of three Saccharomyces cerevisiae acyl-CoA synthetases, Faa1p, Faa2p, and Faa3p. J Biol Chem 269(23):16348-56
12) Knoll LJ, et al.  (1995) Comparison of the reactivity of tetradecenoic acids, a triacsin, and unsaturated oximes with four purified Saccharomyces cerevisiae fatty acid activation proteins. J Biol Chem 270(34):20090-7
13) Choi JY and Martin CE  (1999) The Saccharomyces cerevisiae FAT1 gene encodes an acyl-CoA synthetase that is required for maintenance of very long chain fatty acid levels. J Biol Chem 274(8):4671-83