GFA1/YKL104C Summary Help

Standard Name GFA1 1
Systematic Name YKL104C
Feature Type ORF, Verified
Description Glutamine-fructose-6-phosphate amidotransferase; catalyzes the formation of glucosamine-6-P and glutamate from fructose-6-P and glutamine in the first step of chitin biosynthesis; GFA1 has a paralogous region, comprising ORFs YMR084W-YMR085W, that arose from the whole genome duplication (1, 2, 3 and see Summary Paragraph)
Name Description Glutamine:Fructose-6-phosphate Amidotransferase 1
Chromosomal Location
ChrXI:245373 to 243220 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All GFA1 GO evidence and references
  View Computational GO annotations for GFA1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 7 genes
Resources
Pathways
Classical genetics
unspecified
Large-scale survey
conditional
null
unspecified
Resources
117 total interaction(s) for 95 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 94
  • Affinity Capture-RNA: 3
  • Biochemical Activity: 1
  • Co-purification: 1

Genetic Interactions
  • Dosage Rescue: 4
  • Negative Genetic: 5
  • Phenotypic Enhancement: 2
  • Phenotypic Suppression: 1
  • Positive Genetic: 6

Resources
Expression Summary
histogram
Resources
Length (a.a.) 717
Molecular Weight (Da) 80,046
Isoelectric Point (pI) 6.4
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXI:245373 to 243220 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
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..2154 245373..243220 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 SGDIDS000001587
SUMMARY PARAGRAPH for GFA1

UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) is the source of the first two GlcNAc moieties added during N-linked glycosylation of proteins and provides GlcNAc for synthesis of GPI anchors. In yeast, it is synthesized from fructose-6-phosphate (F6P) by the consecutive action of Gfa1p, Gna1p, Pcm1p, and Qri1p, although a different pathway (4, 5) is used in bacteria. UDP-GlcNAc is also the building block from which chitin, a linear polymer of beta-1,4-N-acetylglucosamine, is constructed. Chitin is a component of the cell wall deposited as a ring around the neck of the growing bud during cell division. Bud scars, the remnants of the chitinous primary septum seen on the surface of mother cells after division, are the primary repository of chitin (reviewed in 6).

GFA1 encodes glutamine:fructose-6-phosphate amidotransferase (GFAT, EC 2.6.1.16), which converts F6P to glucosamine-6-phosphate. Originally called gcn1 (1, 7), mutants are auxotrophic for glucosamine (7), fail to complete sporulation (7, 8), and have altered glycoprotein synthesis (8).

GFA1 is regulated by many of the mechanisms that control the cell cycle. It is induced in response to mating pheromones (1) and the PKC1 MAP kinase cascade (9), and negatively regulated by Glc7p (9). The promoter contains functional binding sites for Mcm1p (10) and Ste12p (11). GFA1 is also induced by perturbation of the cell wall (2, 12, 13), as is chitin synthesis, but only chitin synthesis is induced when glucosamine (which enters the cell as glucosamine-6-P, bypassing Gfa1p) is added to the growth medium (12).

Humans have two enzymes with GFAT activity: Gfpt1 (OMIM) and Gfpt2 (OMIM). Methylmercury (MeHg), a potent toxin to yeast and to humans, targets GFAT in both yeast and human cells (14); overexpression of GFA1 provides resistance by titrating MeHg, not by increasing the strength of the cell wall (14, 15). Candida albicans GFA1 complements deletion of GFA1 in S. cerevisiae (16).

Last updated: 2005-07-01 Contact SGD

References cited on this page View Complete Literature Guide for GFA1
1) Watzele G and Tanner W  (1989) Cloning of the glutamine:fructose-6-phosphate amidotransferase gene from yeast. Pheromonal regulation of its transcription. J Biol Chem 264(15):8753-8
2) Lagorce A, et al.  (2002) Involvement of GFA1, which encodes glutamine-fructose-6-phosphate amidotransferase, in the activation of the chitin synthesis pathway in response to cell-wall defects in Saccharomyces cerevisiae. Eur J Biochem 269(6):1697-707
3) 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
4) Mengin-Lecreulx D and van Heijenoort J  (1993) Identification of the glmU gene encoding N-acetylglucosamine-1-phosphate uridyltransferase in Escherichia coli. J Bacteriol 175(19):6150-7
5) Mengin-Lecreulx D and van Heijenoort J  (1994) Copurification of glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase activities of Escherichia coli: characterization of the glmU gene product as a bifunctional enzyme catalyzing two subsequent steps in the pathway for UDP-N-acetylglucosamine synthesis. J Bacteriol 176(18):5788-95
6) Cid VJ, et al.  (1995) Molecular basis of cell integrity and morphogenesis in Saccharomyces cerevisiae. Microbiol Rev 59(3):345-86
7) Whelan WL and Ballou CE  (1975) Sporulation in D-glucosamine auxotrophs of Saccharomyces cerevisiae: meiosis with defective ascospore wall formation. J Bacteriol 124(3):1545-57
8) Ballou L, et al.  (1981) Temperature-sensitive glucosamine auxotroph of Saccharomyces cerevisiae. Mol Cell Biol 1(1):9-12
9) Zheng J, et al.  (2000) Glc7p protein phosphatase inhibits expression of glutamine-fructose-6-phosphate transaminase from GFA1. J Biol Chem 275(24):18070-8
10) Kuo MH and Grayhack E  (1994) A library of yeast genomic MCM1 binding sites contains genes involved in cell cycle control, cell wall and membrane structure, and metabolism. Mol Cell Biol 14(1):348-59
11) Zeitlinger J, et al.  (2003) Program-specific distribution of a transcription factor dependent on partner transcription factor and MAPK signaling. Cell 113(3):395-404
12) Bulik DA, et al.  (2003) Chitin synthesis in Saccharomyces cerevisiae in response to supplementation of growth medium with glucosamine and cell wall stress. Eukaryot Cell 2(5):886-900
13) Boorsma A, et al.  (2004) Characterization of the transcriptional response to cell wall stress in Saccharomyces cerevisiae. Yeast 21(5):413-27
14) Naganuma A, et al.  (2000) GFAT as a target molecule of methylmercury toxicity in Saccharomyces cerevisiae. FASEB J 14(7):968-72
15) Miura N, et al.  (1999) Overexpression of L-glutamine:D-fructose-6-phosphate amidotransferase provides resistance to methylmercury in Saccharomyces cerevisiae. FEBS Lett 458(2):215-8
16) Smith RJ, et al.  (1996) Isolation and characterization of the GFA1 gene encoding the glutamine:fructose-6-phosphate amidotransferase of Candida albicans. J Bacteriol 178(8):2320-7