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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: Annotation score: 5 out of 5-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

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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi55 – 551MagnesiumBy similarity
Metal bindingi300 – 3001MagnesiumBy similarity
Binding sitei444 – 4441GTP; via amide nitrogenBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi48 – 558GTPBy similarity
Nucleotide bindingi294 – 3007GTPBy similarity
Nucleotide bindingi319 – 3235GTPBy similarity
Nucleotide bindingi388 – 3914GTPBy similarity

GO - Molecular functioni

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
  • heterotrimeric G-protein complex cycle Source: SGD
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Transducer

Keywords - Biological processi

Pheromone response

Keywords - Ligandi

GTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciYEAST:G3O-31070-MONOMER.
ReactomeiR-SCE-416482. G alpha (12/13) signalling events.
R-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

GO - Cellular componenti

  • endosome Source: SGD
  • endosome membrane Source: UniProtKB-SubCell
  • heterotrimeric G-protein complex Source: SGD
  • plasma membrane Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2 – 21G → A: Abolishes both palmitoylation and N-myristoylation. 3 Publications
Mutagenesisi3 – 31C → A: Abolishes palmitoylation but not N-myristoylation. 2 Publications
Mutagenesisi15 – 151D → V: Slightly reduces ligand-dependent pheromone signaling. 1 Publication
Mutagenesisi17 – 171F → L: Leads to a hypersensitive signaling phenotype resulting in greatly enhanced signal at low alpha-factor concentrations. 1 Publication
Mutagenesisi18 – 181L → P or Q: Reduces ligand-dependent pheromone signaling. 1 Publication
Mutagenesisi21 – 222KR → EE: Impairs interaction with FUS3. 1 Publication
Mutagenesisi50 – 501G → D: Confers insensitivity to pheromone. 4 Publications
Mutagenesisi50 – 501G → 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 Publications
Mutagenesisi54 – 541K → E or I: Prevents GDP to GTP exchange; suppressor of L-323. 2 Publications
Mutagenesisi165 – 1651K → R: Substantial decrease in ubiquitination. 1 Publication
Mutagenesisi297 – 2971R → H: Slows hydrolysis of GTP.
Mutagenesisi302 – 3021G → S in GPA1(SST); weakens interaction to SST2 and blocks its negative regulatory effect. 1 Publication
Mutagenesisi321 – 3211G → T: Causes a specific mating defect in alpha cells. 1 Publication
Mutagenesisi322 – 3221G → A, E or R: Confers insensitivity to pheromone. 3 Publications
Mutagenesisi323 – 3231Q → L: Prevents hydrolysis of GTP; eliminates the interaction with STE4 and constitutively activates the pheromone response pathway. 1 Publication
Mutagenesisi327 – 3271R → S: Suppressor of L-323; does not prevent GTP binding to GPA1. 1 Publication
Mutagenesisi345 – 3451A → T: Suppressor of a STE2-L236H mutant. 1 Publication
Mutagenesisi353 – 3531Missing : Suppressor of L-323. 1 Publication
Mutagenesisi355 – 3551E → K: Confers insensitivity to pheromone. 1 Publication
Mutagenesisi364 – 3641E → 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 Publications
Mutagenesisi388 – 3881N → D: Forms a nondissociable complex with the pheromone receptor in response to receptor activation, resulting in reduced pheromone responsiveness. 4 Publications
Mutagenesisi388 – 3881N → K: Causes constitutive activation of the pheromone response pathway. 4 Publications
Mutagenesisi391 – 3911D → A: Causes constitutive activation of the pheromone response pathway. 1 Publication
Mutagenesisi467 – 4671K → P: Impairs pheromone signaling in a and alpha cells. 1 Publication
Mutagenesisi468 – 4681K → P: Impairs pheromone signaling specifically in a cells. 1 Publication
Mutagenesisi470 – 4701G → D: Confers insensitivity to pheromone. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved
Chaini2 – 472471Guanine nucleotide-binding protein alpha-1 subunitPRO_0000203616Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine3 Publications
Lipidationi3 – 31S-palmitoyl cysteine2 Publications
Cross-linki165 – 165Glycyl 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.

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

WithEntry#Exp.IntActNotes
SST2P119723EBI-7376,EBI-18232
STE4P188518EBI-7376,EBI-7390
VPS15P222192EBI-7376,EBI-20347
VPS34P225433EBI-7376,EBI-20405

GO - Molecular functioni

Protein-protein interaction databases

BioGridi36430. 47 interactions.
DIPiDIP-15N.
IntActiP08539. 16 interactions.
MINTiMINT-509090.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1SCGmodel-A1-472[»]
ProteinModelPortaliP08539.
SMRiP08539. Positions 41-136, 240-462.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni127 – 235109Insert; not present in other G-proteinsAdd
BLAST

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

GeneTreeiENSGT00770000120503.
HOGENOMiHOG000038730.
InParanoidiP08539.
KOiK19860.
OMAiISPMKNY.
OrthoDBiEOG092C25Q3.

Family and domain databases

Gene3Di1.10.400.10. 2 hits.
3.40.50.300. 2 hits.
InterProiIPR002975. Fungi_Gprotein_alpha.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR10218. PTHR10218. 2 hits.
PfamiPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSiPR00318. GPROTEINA.
PR01241. GPROTEINAFNG.
SMARTiSM00275. G_alpha. 1 hit.
[Graphical view]
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti82 – 821W → R in AAA18403 (PubMed:3113738).Curated
Sequence conflicti194 – 1941A → V in AAA18403 (PubMed:3113738).Curated
Sequence conflicti226 – 2261R → K in AAA18403 (PubMed:3113738).Curated
Sequence conflicti246 – 2461K → R in AAA18403 (PubMed:3113738).Curated
Sequence conflicti469 – 4691I → S in AAA18403 (PubMed:3113738).Curated

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.

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1SCGmodel-A1-472[»]
ProteinModelPortaliP08539.
SMRiP08539. Positions 41-136, 240-462.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi36430. 47 interactions.
DIPiDIP-15N.
IntActiP08539. 16 interactions.
MINTiMINT-509090.

PTM databases

iPTMnetiP08539.
SwissPalmiP08539.

Proteomic databases

MaxQBiP08539.

Protocols and materials databases

DNASUi856394.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYHR005C; YHR005C; YHR005C.
GeneIDi856394.
KEGGisce:YHR005C.

Organism-specific databases

EuPathDBiFungiDB:YHR005C.
SGDiS000001047. GPA1.

Phylogenomic databases

GeneTreeiENSGT00770000120503.
HOGENOMiHOG000038730.
InParanoidiP08539.
KOiK19860.
OMAiISPMKNY.
OrthoDBiEOG092C25Q3.

Enzyme and pathway databases

BioCyciYEAST:G3O-31070-MONOMER.
ReactomeiR-SCE-416482. G alpha (12/13) signalling events.
R-SCE-418555. G alpha (s) signalling events.

Miscellaneous databases

PROiP08539.

Family and domain databases

Gene3Di1.10.400.10. 2 hits.
3.40.50.300. 2 hits.
InterProiIPR002975. Fungi_Gprotein_alpha.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR10218. PTHR10218. 2 hits.
PfamiPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSiPR00318. GPROTEINA.
PR01241. GPROTEINAFNG.
SMARTiSM00275. G_alpha. 1 hit.
[Graphical view]
SUPFAMiSSF47895. SSF47895. 2 hits.
SSF52540. SSF52540. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiGPA1_YEAST
AccessioniPrimary (citable) accession number: P08539
Secondary accession number(s): D3DKU8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 184 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.