GPA1/YHR005C Summary Help

Standard Name GPA1 1
Systematic Name YHR005C
Alias CDC70 2 , DAC1 3 , SCG1 4
Feature Type ORF, Verified
Description Subunit of the G protein involved in pheromone response; GTP-binding alpha subunit of the heterotrimeric G protein; negatively regulates the mating pathway by sequestering G(beta)gamma and by triggering an adaptive response; activates Vps34p at the endosome; protein abundance increases in response to DNA replication stress (5, 6, 7, 8 and see Summary Paragraph)
Name Description G Protein Alpha subunit 1
Chromosomal Location
ChrVIII:114917 to 113499 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 3 cM
Gene Ontology Annotations All GPA1 GO evidence and references
  View Computational GO annotations for GPA1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 12 genes
Resources
Classical genetics
conditional
null
overexpression
reduction of function
repressible
Large-scale survey
null
reduction of function
repressible
Resources
106 total interaction(s) for 44 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 7
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 35
  • Biochemical Activity: 6
  • Co-fractionation: 1
  • Co-localization: 1
  • Co-purification: 2
  • FRET: 1
  • PCA: 1
  • Reconstituted Complex: 8
  • Two-hybrid: 12

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 7
  • Phenotypic Suppression: 5
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 3
  • Synthetic Rescue: 13

Resources
Expression Summary
histogram
Resources
Length (a.a.) 472
Molecular Weight (Da) 54,075
Isoelectric Point (pI) 7.58
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVIII:114917 to 113499 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 3 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1419 114917..113499 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 | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001047
SUMMARY PARAGRAPH for GPA1

Gpa1p encodes a guanine nucleotide binding protein that functions as a subunit of the heterotrimeric G protein involved in the pheromone response pathway (4, 9). Haploid yeast cells exist as one of two mating types, MATa or MATalpha. Mating of haploid cells to form diploids is initiated when the peptide pheromones produced by either cell type (a factor or alpha factor) bind to seven-transmembrane receptor proteins on cells of the opposite type: Ste2p (MATa cells) or Ste3p (MATalpha cells) (10, 11). Pheromone binding leads to activation of the heterotrimeric G-protein composed of alpha subunit Gpa1p, beta subunit Ste4p, and gamma subunit Ste18p (12, 4, 9). Activation is mediated by exchange of GDP for GTP on the alpha subunit, causing the heterotrimer to dissociate. The resulting Ste4p-Ste18p dimer mediates signal transduction through binding to both the scaffolding protein Ste5p and the PAK kinase Ste20p, causing activation of a MAP kinase cascade (Ste11p, Ste7p, and Fus3p; 13, 14). The Ste4p-Ste18p dimer also interacts with a complex of Far1p and Cdc24p; in total, these interactions induce expression of genes involved in mating, polarization of cell growth, and ultimately cell and nuclear fusion (reviewed in 15).

There are at least two mechanisms by which GTP-bound Gpa1p mediates dampening of the pheromone-induced signal. First, Gpa1p has intrinsic GTP hydrolysis activity, which is stimulated by interaction with the RGS (regulators of G protein signaling) protein Sst2p (16). Hydrolysis of GTP converts Gpa1p back to the GDP-bound form, which can then sequester the active Ste4p-Ste18p complex into the inactive heterotrimer (reviewed in 15 and 17). Second, Gpa1p interacts with the MAP kinase Fus3p, and this interaction antagonizes the pheromone-induced accumulation of Fus3p in the nucleus (18).

In its role of mediating pheromone response, Gpa1p localizes to the plasma membrane, facilitated by myristoylation and palmitoylation of two tandem amino acids at the N-terminus (19, 20), modifications which are critical for normal pheromone signaling (21). Gpa1p also plays a role in pheromone signaling in the endosome (independent of Ste4p and Ste18p), where it interacts with the Vps34p-Vps15p phosphatidylinositol (PtdIns) 3-kinase (7). The GTP-bound form of Gpa1p binds to the catalytic Vps34p subunit to promote increased PtdIns 3-P production, which is sufficient to recruit the PtdIns 3-P binding protein Bem1p to the endosome. The GDP-bound form of Gpa1p binds the regulatory Vps15p subunit, which may function to dampen the signal, analogous to the Ste4p-Ste18p interaction (7).

G-protein-coupled receptor signaling mechanisms are conserved in eukaryotes, and S. cerevisiae has become an attractive expression system for studying human GPCRs and performing high-throughput screens for unknown ligands or for new drugs (22). Human genome sequencing has revealed 16 alpha subunits that comprise four functional groups; the closest homolog to Gpa1p is GNAI2, mutations in which have been associated with some adrenal tumors (23, reviewed in 24 and 15). Mutations in GNAS are associated with Albright hereditary osteodystrophy (AHO), pseudohypoparathyroidism type Ia (PHP Ia), and pseudopseudohypoparathyroidism OMIM (25, 26).

Last updated: 2007-05-31 Contact SGD

References cited on this page View Complete Literature Guide for GPA1
1) Nakafuku M, et al.  (1987) Occurrence in Saccharomyces cerevisiae of a gene homologous to the cDNA coding for the alpha subunit of mammalian G proteins. Proc Natl Acad Sci U S A 84(8):2140-4
2) Jahng KY, et al.  (1988) Mutations in a gene encoding the alpha subunit of a Saccharomyces cerevisiae G protein indicate a role in mating pheromone signaling. Mol Cell Biol 8(6):2484-93
3) Fujimura HA  (1989) The yeast G-protein homolog is involved in the mating pheromone signal transduction system. Mol Cell Biol 9(1):152-8
4) Dietzel C and Kurjan J  (1987) The yeast SCG1 gene: a G alpha-like protein implicated in the a- and alpha-factor response pathway. Cell 50(7):1001-10
5) Dohlman HG and Thorner JW  (2001) Regulation of G protein-initiated signal transduction in yeast: paradigms and principles. Annu Rev Biochem 70():703-54
6) Guo M, et al.  (2003) The yeast G protein alpha subunit Gpa1 transmits a signal through an RNA binding effector protein Scp160. Mol Cell 12(2):517-24
7) Slessareva JE, et al.  (2006) Activation of the phosphatidylinositol 3-kinase Vps34 by a G protein alpha subunit at the endosome. Cell 126(1):191-203
8) 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
9) Miyajima I, et al.  (1987) GPA1, a haploid-specific essential gene, encodes a yeast homolog of mammalian G protein which may be involved in mating factor signal transduction. Cell 50(7):1011-9
10) Burkholder AC and Hartwell LH  (1985) The yeast alpha-factor receptor: structural properties deduced from the sequence of the STE2 gene. Nucleic Acids Res 13(23):8463-75
11) Hagen DC, et al.  (1986) Evidence the yeast STE3 gene encodes a receptor for the peptide pheromone a factor: gene sequence and implications for the structure of the presumed receptor. Proc Natl Acad Sci U S A 83(5):1418-22
12) Whiteway M, et al.  (1989) The STE4 and STE18 genes of yeast encode potential beta and gamma subunits of the mating factor receptor-coupled G protein. Cell 56(3):467-77
13) Leeuw T, et al.  (1998) Interaction of a G-protein beta-subunit with a conserved sequence in Ste20/PAK family protein kinases. Nature 391(6663):191-5
14) Dowell SJ, et al.  (1998) Mapping of a yeast G protein betagamma signaling interaction. Genetics 150(4):1407-17
15) Bardwell L  (2005) A walk-through of the yeast mating pheromone response pathway. Peptides 26(2):339-50
16) Apanovitch DM, et al.  (1998) Sst2 is a GTPase-activating protein for Gpa1: purification and characterization of a cognate RGS-Galpha protein pair in yeast. Biochemistry 37(14):4815-22
17) Dohlman HG and Thorner J  (1997) RGS proteins and signaling by heterotrimeric G proteins. J Biol Chem 272(7):3871-4
18) Blackwell E, et al.  (2003) Effect of the pheromone-responsive G(alpha) and phosphatase proteins of Saccharomyces cerevisiae on the subcellular localization of the Fus3 mitogen-activated protein kinase. Mol Cell Biol 23(4):1135-50
19) Song J, et al.  (1996) Regulation of membrane and subunit interactions by N-myristoylation of a G protein alpha subunit in yeast. J Biol Chem 271(34):20273-83
20) Song J and Dohlman HG  (1996) Partial constitutive activation of pheromone responses by a palmitoylation-site mutant of a G protein alpha subunit in yeast. Biochemistry 35(47):14806-17
21) Manahan CL, et al.  (2000) Dual lipid modification motifs in G(alpha) and G(gamma) subunits are required for full activity of the pheromone response pathway in Saccharomyces cerevisiae. Mol Biol Cell 11(3):957-68
22) Minic J, et al.  (2005) Yeast system as a screening tool for pharmacological assessment of g protein coupled receptors. Curr Med Chem 12(8):961-9
23) Lyons J, et al.  (1990) Two G protein oncogenes in human endocrine tumors. Science 249(4969):655-9
24) Robishaw JD and Berlot CH  (2004) Translating G protein subunit diversity into functional specificity. Curr Opin Cell Biol 16(2):206-9
25) Levine MA, et al.  (1988) Genetic deficiency of the alpha subunit of the guanine nucleotide-binding protein Gs as the molecular basis for Albright hereditary osteodystrophy. Proc Natl Acad Sci U S A 85(2):617-21
26) Weinstein LS, et al.  (1990) Mutations of the Gs alpha-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis. Proc Natl Acad Sci U S A 87(21):8287-90