FAS1/YKL182W Summary Help

Standard Name FAS1
Systematic Name YKL182W
Feature Type ORF, Verified
Description Beta subunit of fatty acid synthetase; complex catalyzes the synthesis of long-chain saturated fatty acids; contains acetyltransacylase, dehydratase, enoyl reductase, malonyl transacylase, and palmitoyl transacylase activities (1 and see Summary Paragraph)
Name Description Fatty Acid Synthetase
Chromosomal Location
ChrXI:100671 to 106826 | ORF Map | GBrowse
Gbrowse
Genetic position: -116.7 cM
Gene Ontology Annotations All FAS1 GO evidence and references
  View Computational GO annotations for FAS1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 70 genes
Resources
Pathways
Classical genetics
conditional
null
overexpression
Large-scale survey
null
reduction of function
Resources
84 total interaction(s) for 66 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 50
  • Affinity Capture-RNA: 5
  • Affinity Capture-Western: 2
  • PCA: 1
  • Reconstituted Complex: 1

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 2
  • Negative Genetic: 15
  • Phenotypic Enhancement: 1
  • Positive Genetic: 5
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 2,051
Molecular Weight (Da) 228,689
Isoelectric Point (pI) 5.79
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXI:100671 to 106826 | ORF Map | GBrowse
SGD ORF map
Genetic position: -116.7 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..6156 100671..106826 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 SGDIDS000001665
SUMMARY PARAGRAPH for FAS1

Fatty acids are essential components of eukaryotic and bacterial (but not archaeal) cells, where they are used in membrane synthesis, energy storage and protein modification. Most cells are capable of synthesizing, long chain saturated fatty acids de novo, using acetyl-CoA as a starting substrate. Fatty acid biosynthesis is essentially the same across organisms. In an iterative process, the growing fatty acid chain is gradually extended, two carbons at a time, until the final length is achieved. Each addition requires seven different catalytic activities as well as a pantetheinylated acyl-carrier protein, to which the growing fatty acid chain is attached (see fatty acid biosynthesis pathways: initial steps and elongation). In S. cerevisiae, palmitoleic (C16) and oleic (C18) acyl-CoAs are the most common products of this process. Although the biochemistry is similar across phylogeny, the physical organization of the catalytic sites varies between organisms. Plants, mitochondria and most bacteria have type II Fatty Acid Synthase (FAS II) systems, where each enzymatic activity is encoded by an individual, disassociated protein. Fungi, animals and some bacteria have type I Fatty Acid Synthase (FAS I) systems involving complexes of multifunctional proteins. In humans, for example, only the enzyme catalyzing the first step in fatty acid synthesis (the formation of malonyl-CoA by acetyl-CoA carboxylase, EC:6.4.1.2) is a separate protein; all other activities are contained within a single polypeptide, ACSL1, which forms an X-shaped homodimer complex (reviewed in 2, 3, 4, 5, 6).

In S. cerevisiae, as in humans, only the acetyl-CoA carboxylase activity (Acc1p) is separate. In contrast to humans, however, the other activities are distributed between two proteins, Fas1p and Fas2p, the beta and alpha subunits of a large, barrel-shaped complex containing 6 copies of each protein (alpha6beta6) (7, 8). Together, the six Fas1p and six Fas2p subunits form six independent reaction centers, each containing all enzyme activities required for synthesizing long chain fatty acids from acetyl- and malony-CoA (9, 10, and references therein). FAS1 encodes four independent enzymatic functions: acetyltransferase (EC:2.3.1.38), enoyl reductase (EC:1.3.1.10), dehydratase (EC:4.2.1.61), and malonyl/palmitoyl-transferase (EC:2.3.1.39) (11, 1, 12, 13). FAS2 encodes the acyl-carrier protein domain and three independent enzymatic functions: 3-ketoreductase (EC:1.1.1.100), 3-ketosynthase (EC:2.3.1.41) and phosphopantetheinyl transferase (EC:2.7.8.7) (11, 14, 15). This last enzymatic activity is not part of fatty acid biosynthesis, but rather is responsible for the pantetheinylation of the acyl-carrier protein domain (15 and references therein). This post-translational modification is essential for FAS I activity and is thought to allow movement of the growing fatty acid chain between the different catalytic sites in each reaction center. In humans, the phosphopantetheinyl transferase activity is catalyzed by a separate enzyme that is disassociated from the FAS I complex, AASDHPPT (6, 16 and references therein).

As "housekeeping" genes, FAS1 and FAS2 are constitutively activated by general transcription factors Rap1p, Abf1p, and Reb1p (17). Both FAS1 and FAS2 are further activated by the inositol/choline-responsive transcription factor heteroduplex, Ino2p-Ino4p (18, 19). In addition, Fas1p and Fas2p stoichiometry appears to be insured by a regulatory mechanism in which FAS1 protein controls FAS2 mRNA levels (20).

Last updated: 2010-04-24 Contact SGD

References cited on this page View Complete Literature Guide for FAS1
1) Schweizer M, et al.  (1986) The pentafunctional FAS1 gene of yeast: its nucleotide sequence and order of the catalytic domains. Mol Gen Genet 203(3):479-86
2) Lynen F  (1980) On the structure of fatty acid synthetase of yeast. Eur J Biochem 112(3):431-42
3) Schweizer E and Hofmann J  (2004) Microbial type I fatty acid synthases (FAS): major players in a network of cellular FAS systems. Microbiol Mol Biol Rev 68(3):501-17, table of contents
4) Tehlivets O, et al.  (2007) Fatty acid synthesis and elongation in yeast. Biochim Biophys Acta 1771(3):255-70
5) Kolter T  (2007) The Fatty Acid Factory of Yeasts. Angew Chem Int Ed Engl 46(36):6772-6775
6) Leibundgut M, et al.  (2008) The multienzyme architecture of eukaryotic fatty acid synthases. Curr Opin Struct Biol 18(6):714-25
7) Wieland F, et al.  (1978) Distribution of yeast fatty acid synthetase subunits: three-dimensional model of the enzyme. Proc Natl Acad Sci U S A 75(12):5792-6
8) Kolodziej SJ, et al.  (1996) Structure-function relationships of the Saccharomyces cerevisiae fatty acid synthase. Three-dimensional structure. J Biol Chem 271(45):28422-9
9) Leibundgut M, et al.  (2007) Structural basis for substrate delivery by acyl carrier protein in the yeast fatty acid synthase. Science 316(5822):288-90
10) Lomakin IB, et al.  (2007) The crystal structure of yeast fatty acid synthase, a cellular machine with eight active sites working together. Cell 129(2):319-32
11) Stoops JK and Wakil SJ  (1978) The isolation of the two subunits of yeast fatty acid synthetase. Biochem Biophys Res Commun 84(1):225-31
12) Wieland F, et al.  (1979) Studies on the multi-enzyme complex of yeast fatty-acid synthetase. Reversible dissociation and isolation of two polypeptide chains. Eur J Biochem 94(1):189-97
13) Kottig H, et al.  (1991) The pentafunctional FAS1 genes of Saccharomyces cerevisiae and Yarrowia lipolytica are co-linear and considerably longer than previously estimated. Mol Gen Genet 226(1-2):310-4
14) Mohamed AH, et al.  (1988) Primary structure of the multifunctional alpha subunit protein of yeast fatty acid synthase derived from FAS2 gene sequence. J Biol Chem 263(25):12315-25
15) Fichtlscherer F, et al.  (2000) A novel function of yeast fatty acid synthase. Subunit alpha is capable of self-pantetheinylation. Eur J Biochem 267(9):2666-71
16) Bunkoczi G, et al.  (2007) Mechanism and substrate recognition of human holo ACP synthase. Chem Biol 14(11):1243-53
17) Schuller HJ, et al.  (1994) Importance of general regulatory factors Rap1p, Abf1p and Reb1p for the activation of yeast fatty acid synthase genes FAS1 and FAS2. Eur J Biochem 225(1):213-22
18) Schuller HJ, et al.  (1992) Regulatory gene INO4 of yeast phospholipid biosynthesis is positively autoregulated and functions as a transactivator of fatty acid synthase genes FAS1 and FAS2 from Saccharomyces cerevisiae. Nucleic Acids Res 20(22):5955-61
19) Schwank S, et al.  (1995) Yeast transcriptional activator INO2 interacts as an Ino2p/Ino4p basic helix-loop-helix heteromeric complex with the inositol/choline-responsive element necessary for expression of phospholipid biosynthetic genes in Saccharomyces cerevisiae. Nucleic Acids Res 23(2):230-7
20) Wenz P, et al.  (2001) A downstream regulatory element located within the coding sequence mediates autoregulated expression of the yeast fatty acid synthase gene FAS2 by the FAS1 gene product. Nucleic Acids Res 29(22):4625-32