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Protein

Guanine nucleotide-binding protein alpha-1 subunit

Gene

GPA1

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.20 Publications

Miscellaneous

Present with 9920 molecules/cell in log phase SD medium.1 Publication

Enzyme regulationi

Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by the G protein coupled receptors (GPCRs) STE2 and STE3, which serve as guanine nucleotide-exchange factors (GEFs), and inactivated by SST2, probably acting as a GTPase-activating protein (GAP).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi55MagnesiumBy similarity1
Metal bindingi300MagnesiumBy similarity1
Binding sitei444GTP; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi48 – 55GTPBy similarity8
Nucleotide bindingi294 – 300GTPBy similarity7
Nucleotide bindingi319 – 323GTPBy similarity5
Nucleotide bindingi388 – 391GTPBy similarity4

GO - Molecular functioni

  • G-protein beta/gamma-subunit complex binding Source: GO_Central
  • G-protein beta-subunit binding Source: SGD
  • G-protein coupled receptor binding Source: GO_Central
  • GTPase activity Source: SGD
  • GTP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • adaptation of signaling pathway by response to pheromone involved in conjugation with cellular fusion Source: SGD
  • adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: GO_Central
  • inositol lipid-mediated signaling Source: SGD
  • karyogamy involved in conjugation with cellular fusion Source: SGD
  • nuclear migration involved in conjugation with cellular fusion Source: SGD
  • pheromone-dependent signal transduction involved in conjugation with cellular fusion Source: SGD
  • regulation of MAPK export from nucleus Source: SGD

Keywordsi

Molecular functionTransducer
Biological processPheromone response
LigandGTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciYEAST:G3O-31070-MONOMER
ReactomeiR-SCE-418555 G alpha (s) signalling events

Names & Taxonomyi

Protein namesi
Recommended name:
Guanine nucleotide-binding protein alpha-1 subunit
Alternative name(s):
GP1-alpha
Gene namesi
Name:GPA1
Synonyms:CDC70, DAC1, SCG1
Ordered Locus Names:YHR005C
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome VIII

Organism-specific databases

EuPathDBiFungiDB:YHR005C
SGDiS000001047 GPA1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cell wall Cytoskeleton Vacuole Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2G → A: Abolishes both palmitoylation and N-myristoylation. 3 Publications1
Mutagenesisi3C → A: Abolishes palmitoylation but not N-myristoylation. 2 Publications1
Mutagenesisi15D → V: Slightly reduces ligand-dependent pheromone signaling. 1 Publication1
Mutagenesisi17F → L: Leads to a hypersensitive signaling phenotype resulting in greatly enhanced signal at low alpha-factor concentrations. 1 Publication1
Mutagenesisi18L → P or Q: Reduces ligand-dependent pheromone signaling. 1 Publication1
Mutagenesisi21 – 22KR → EE: Impairs interaction with FUS3. 1 Publication2
Mutagenesisi50G → D: Confers insensitivity to pheromone. 4 Publications1
Mutagenesisi50G → V: Has increased GTP occupancy and moderately reduces hydrolysis of GTP, resulting in a constitutively active form that down-regulates the pheromone response and causes hyperadaptation to pheromone. 4 Publications1
Mutagenesisi54K → E or I: Prevents GDP to GTP exchange; suppressor of L-323. 2 Publications1
Mutagenesisi165K → R: Substantial decrease in ubiquitination. 1 Publication1
Mutagenesisi297R → H: Slows hydrolysis of GTP. 1
Mutagenesisi302G → S in GPA1(SST); weakens interaction to SST2 and blocks its negative regulatory effect. 1 Publication1
Mutagenesisi321G → T: Causes a specific mating defect in alpha cells. 1 Publication1
Mutagenesisi322G → A, E or R: Confers insensitivity to pheromone. 3 Publications1
Mutagenesisi323Q → L: Prevents hydrolysis of GTP; eliminates the interaction with STE4 and constitutively activates the pheromone response pathway. 1 Publication1
Mutagenesisi327R → S: Suppressor of L-323; does not prevent GTP binding to GPA1. 1 Publication1
Mutagenesisi345A → T: Suppressor of a STE2-L236H mutant. 1 Publication1
Mutagenesisi353Missing : Suppressor of L-323. 1 Publication1
Mutagenesisi355E → K: Confers insensitivity to pheromone. 1 Publication1
Mutagenesisi364E → K: Enhances the rate of GDP for GTP exchange and slows hydrolysis of GTP, resulting in a constitutively active form that down-regulates the pheromone response independently of the pheromone receptor. 3 Publications1
Mutagenesisi388N → D: Forms a nondissociable complex with the pheromone receptor in response to receptor activation, resulting in reduced pheromone responsiveness. 4 Publications1
Mutagenesisi388N → K: Causes constitutive activation of the pheromone response pathway. 4 Publications1
Mutagenesisi391D → A: Causes constitutive activation of the pheromone response pathway. 1 Publication1
Mutagenesisi467K → P: Impairs pheromone signaling in a and alpha cells. 1 Publication1
Mutagenesisi468K → P: Impairs pheromone signaling specifically in a cells. 1 Publication1
Mutagenesisi470G → D: Confers insensitivity to pheromone. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00002036162 – 472Guanine nucleotide-binding protein alpha-1 subunitAdd BLAST471

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine3 Publications1
Lipidationi3S-palmitoyl cysteine2 Publications1
Cross-linki165Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

N-myristoylation by NMT1 is pheromone-stimulated and required for palmitoylation of Cys-3. This lipid modification anchors the protein to membranes. Depalmitoylated by YLR118C/APT1.5 Publications
Monoubiquitination targets the protein for degradation to the vacuole, and polyubiquitination tags the protein for degradation by the proteasome. This may be an additional signaling regulation mechanism.1 Publication

Keywords - PTMi

Isopeptide bond, Lipoprotein, Myristate, Palmitate, Ubl conjugation

Proteomic databases

MaxQBiP08539
PaxDbiP08539
PRIDEiP08539

PTM databases

iPTMnetiP08539
SwissPalmiP08539

Interactioni

Subunit structurei

G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. In its GDP-bound form, binds to the G protein beta-gamma dimer STE4-STE18. Directly interacts with the beta subunit STE4. Probably forms preactivation complexes with unligated receptors STE2 and STE3. Interacts with FUS3. Pheromone-induced activation of GPA1 increases its association with FUS3. Interacts with SCP160. SCP160 binds specifically to the GTP-bound form of GPA1. Interacts with the phoshpatidylinositol 3-kinase (PI3K) subunits VPS15 and VPS34 at the endosome. The GTP-bound form of GPA1 binds directly and selectively to the catalytic subunit VPS34, while the GDP-bound form binds to VPS15, which appears to function as an alternative G protein beta subunit for GPA1. Interacts with regulators of G protein signaling (RGS) proteins MDM1, RAX1, RGS2 and SST2, but SST2 alone binds preferentially to the transition state conformation of GPA1, indicating that it acts as a GAP for this G protein.7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • G-protein beta-subunit binding Source: SGD
  • G-protein coupled receptor binding Source: GO_Central

Protein-protein interaction databases

BioGridi36430, 53 interactors
ComplexPortaliCPX-1646 G protein heterotrimer
DIPiDIP-15N
IntActiP08539, 20 interactors
MINTiP08539
STRINGi4932.YHR005C

Structurei

3D structure databases

ProteinModelPortaliP08539
SMRiP08539
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni127 – 235Insert; not present in other G-proteinsAdd BLAST109

Domaini

Contains an 'insertion' sequence of 109 residues which is not present in other G-protein alpha chains.

Sequence similaritiesi

Belongs to the G-alpha family. G(q) subfamily.Curated

Phylogenomic databases

GeneTreeiENSGT00910000144108
HOGENOMiHOG000038730
InParanoidiP08539
KOiK19860
OMAiVARMEDT
OrthoDBiEOG092C25Q3

Family and domain databases

CDDicd00066 G-alpha, 1 hit
Gene3Di1.10.400.10, 2 hits
InterProiView protein in InterPro
IPR002975 Fungi_Gprotein_alpha
IPR001019 Gprotein_alpha_su
IPR011025 GproteinA_insert
IPR027417 P-loop_NTPase
PANTHERiPTHR10218 PTHR10218, 1 hit
PfamiView protein in Pfam
PF00503 G-alpha, 1 hit
PRINTSiPR00318 GPROTEINA
PR01241 GPROTEINAFNG
SMARTiView protein in SMART
SM00275 G_alpha, 1 hit
SUPFAMiSSF47895 SSF47895, 2 hits
SSF52540 SSF52540, 2 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P08539-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCTVSTQTI GDESDPFLQN KRANDVIEQS LQLEKQRDKN EIKLLLLGAG
60 70 80 90 100
ESGKSTVLKQ LKLLHQGGFS HQERLQYAQV IWADAIQSMK ILIIQARKLG
110 120 130 140 150
IQLDCDDPIN NKDLFACKRI LLKAKALDYI NASVAGGSDF LNDYVLKYSE
160 170 180 190 200
RYETRRRVQS TGRAKAAFDE DGNISNVKSD TDRDAETVTQ NEDADRNNSS
210 220 230 240 250
RINLQDICKD LNQEGDDQMF VRKTSREIQG QNRRNLIHED IAKAIKQLWN
260 270 280 290 300
NDKGIKQCFA RSNEFQLEGS AAYYFDNIEK FASPNYVCTD EDILKGRIKT
310 320 330 340 350
TGITETEFNI GSSKFKVLDA GGQRSERKKW IHCFEGITAV LFVLAMSEYD
360 370 380 390 400
QMLFEDERVN RMHESIMLFD TLLNSKWFKD TPFILFLNKI DLFEEKVKSM
410 420 430 440 450
PIRKYFPDYQ GRVGDAEAGL KYFEKIFLSL NKTNKPIYVK RTCATDTQTM
460 470
KFVLSAVTDL IIQQNLKKIG II
Length:472
Mass (Da):54,076
Last modified:January 23, 2007 - v3
Checksum:i2E87C546E133D6E5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti82W → R in AAA18403 (PubMed:3113738).Curated1
Sequence conflicti194A → V in AAA18403 (PubMed:3113738).Curated1
Sequence conflicti226R → K in AAA18403 (PubMed:3113738).Curated1
Sequence conflicti246K → R in AAA18403 (PubMed:3113738).Curated1
Sequence conflicti469I → S in AAA18403 (PubMed:3113738).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M15867 Genomic DNA Translation: AAA34650.1
M17414 Unassigned DNA Translation: AAA18403.1
U10555 Genomic DNA Translation: AAB68432.1
AY692963 Genomic DNA Translation: AAT92982.1
BK006934 Genomic DNA Translation: DAA06692.1
PIRiA25906
RefSeqiNP_011868.1, NM_001179135.1

Genome annotation databases

EnsemblFungiiYHR005C; YHR005C; YHR005C
GeneIDi856394
KEGGisce:YHR005C

Similar proteinsi

Entry informationi

Entry nameiGPA1_YEAST
AccessioniPrimary (citable) accession number: P08539
Secondary accession number(s): D3DKU8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 201 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome VIII
    Yeast (Saccharomyces cerevisiae) chromosome VIII: entries and gene names

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