LipidDB ID

LipidDB-559292-01343

Entry Name

UniProt Accession

P08539; D3DKU8;

Theoretical PI

7.5

Molecular Weight

54075.56

Genbank Protein ID

AAA34650.1; AAA18403.1; AAB68432.1; AAT92982.1; DAA06692.1;

Genbank Nucleotide ID

M15867; M17414; U10555; AY692963; BK006934;

Protein Name

Guanine nucleotide-binding protein alpha-1 subunit

Protein Synonyms/Alias

GP1-alpha;

Gene Name

GPA1

Gene Synonyms/Alias

CDC70; DAC1; SCG1; YHR005C;

Created Date

01-AUG-1988

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

NCBI Taxa ID

559292

Reference

[1] Song J, Dohlman HG. Partial constitutive activation of pheromone responses by a palmitoylation-site mutant of a G protein alpha subunit in yeast. Biochemistry.1996 Nov 26;35(47):14806-17.[PMID:8942643]
[2] Manahan CL, Patnana M, Blumer KJ, Linder ME. Dual lipid modification motifs inG(alpha) and G(gamma) subunits are required for full activity of the pheromoneresponse pathway in Saccharomyces cerevisiae. Mol Biol Cell. 2000Mar;11(3):957-68.[PMID:10712512]
[3] Duncan JA, Gilman AG. Characterization of Saccharomyces cerevisiaeacyl-protein thioesterase 1, the enzyme responsible for G protein alpha subunitdeacylation in vivo. J Biol Chem. 2002 Aug 30;277(35):31740-52. Epub 2002 Jun 21.[PMID:12080046]
[4] Dohlman HG, Goldsmith P, Spiegel AM, Thorner J. Pheromone action regulatesG-protein alpha-subunit myristoylation in the yeast Saccharomyces cerevisiae.Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9688-92.[PMID:8415763]
[5] Song J, Hirschman J, Gunn K, Dohlman HG. Regulation of membrane and subunitinteractions by N-myristoylation of a G protein alpha subunit in yeast. J BiolChem. 1996 Aug 23;271(34):20273-83.[PMID:8702760]
[6] Stone DE, Cole GM, de Barros Lopes M, Goebl M, Reed SI. N-myristoylation isrequired for function of the pheromone-responsive G alpha protein of yeast:conditional activation of the pheromone response by a temperature-sensitiveN-myristoyl transferase. Genes Dev. 1991 Nov;5(11):1969-81.[PMID:1936988]

Functional Description

Alpha subunit of the heterotrimeric guanine nucleotide- binding protein (G protein) that mediates mating pheromone signal transduction. Binding of alpha-factor or a-factor to its cognate transmembrane receptor STE2 and STE3, respectively, allows the receptor to serve as a guanine nucleotide exchange factor (GEF) on GPA1. The exchange of GDP for GTP on the G protein alpha subunit alters its interaction with the G protein beta subunit STE4, leading to dissociation of the G protein beta-gamma dimer STE4- STE18. The dissociated subunits activate downstream effectors to activate the mating response pathway and induce changes necessary to produce mating-competent cells. STE4-STE18 activate the downstream pheromone signaling MAP kinase cascade leading to expression of mating-specific genes, inducing cell cycle arrest in G1, promoting polarized cell growth to form mating projections (shmoos), and establishing the changes in plasma membrane, cell wall and nuclear envelope to permit cell-cell fusion (plasmogamy) and fusion of the two haploid nuclei (karyogamy). GPA1 transmits a signal that requires direct binding to the effector enzyme PI3K located at the endosome, promoting increased PI3 production. The intrinsic GTPase activity of GPA1 determines the duration of signaling, and is dramatically accelerated by the RGS protein SST2. In unstimulated cells, GDP-bound GPA1 sequesters the G protein beta-gamma subunit STE4-STE18, preventing it from activating the downstream effectors. Also down-regulates the signal by inhibiting the pheromone-induced accumulation of FUS3 in the nucleus.

Sequence Annotation

Nucleotide-binding: 48 55 GTP.
Nucleotide-binding: 294 300 GTP.
Nucleotide-binding: 319 323 GTP.
Nucleotide-binding: 388 391 GTP.
Region: 127 235 Insert; not present in other G-proteins.
Metal binding site: 55 55 Magnesium.
Metal binding site: 300 300 Magnesium.
Binding site: 444 444 GTP; via amide nitrogen.

Protein Length

472 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0005768; C:endosome; IDA:SGD
GO:0005834; C:heterotrimeric G-protein complex; IDA:SGD
GO:0005886; C:plasma membrane; IDA:SGD
GO:0005525; F:GTP binding; IEA:UniProtKB-KW
GO:0003924; F:GTPase activity; IDA:SGD
GO:0046872; F:metal ion binding; IEA:UniProtKB-KW
GO:0004871; F:signal transducer activity; IEA:UniProtKB-KW
GO:0000754; P:adaptation of signaling pathway by response to pheromone involved in conjugation with cellular fusion; IMP:SGD
GO:0007189; P:adenylate cyclase-activating G-protein coupled receptor signaling pathway; IEA:InterPro
GO:0031684; P:heterotrimeric G-protein complex cycle; IMP:SGD
GO:0048017; P:inositol lipid-mediated signaling; IMP:SGD
GO:0000742; P:karyogamy involved in conjugation with cellular fusion; IMP:SGD
GO:0000743; P:nuclear migration involved in conjugation with cellular fusion; IMP:SGD
GO:0000750; P:pheromone-dependent signal transduction involved in conjugation with cellular fusion; IMP:SGD
GO:0071701; P:regulation of MAPK export from nucleus; IMP:SGD

Interpro

InterPro; IPR002975; Fungi_Gprotein_alpha
InterPro; IPR001019; Gprotein_alpha_su
InterPro; IPR011025; GproteinA_insert
InterPro; IPR027417; P-loop_NTPase

Pfam

Pfam; PF00503; G-alpha;

SMART

SMART; SM00275; G_alpha;

PROSITE

PRINTS

PRINTS; PR00318; GPROTEINA;
PRINTS; PR01241; GPROTEINAFNG;