Gene/Proteome Database (LMPD)
Proteins
| guanine nucleotide-binding protein subunit alpha | |
|---|---|
| Refseq ID | NP_011868 |
| Protein GI | 6321792 |
| UniProt ID | P08539 |
| mRNA ID | NM_001179135 |
| Length | 472 |
| RefSeq Status | PROVISIONAL |
| MGCTVSTQTIGDESDPFLQNKRANDVIEQSLQLEKQRDKNEIKLLLLGAGESGKSTVLKQLKLLHQGGFSHQERLQYAQVIWADAIQSMKILIIQARKLGIQLDCDDPINNKDLFACKRILLKAKALDYINASVAGGSDFLNDYVLKYSERYETRRRVQSTGRAKAAFDEDGNISNVKSDTDRDAETVTQNEDADRNNSSRINLQDICKDLNQEGDDQMFVRKTSREIQGQNRRNLIHEDIAKAIKQLWNNDKGIKQCFARSNEFQLEGSAAYYFDNIEKFASPNYVCTDEDILKGRIKTTGITETEFNIGSSKFKVLDAGGQRSERKKWIHCFEGITAVLFVLAMSEYDQMLFEDERVNRMHESIMLFDTLLNSKWFKDTPFILFLNKIDLFEEKVKSMPIRKYFPDYQGRVGDAEAGLKYFEKIFLSLNKTNKPIYVKRTCATDTQTMKFVLSAVTDLIIQQNLKKIGII | |
Gene Information
Entrez Gene ID
Gene Name
guanine nucleotide-binding protein subunit alpha
Gene Symbol
Species
Saccharomyces cerevisiae S288c
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005768 | IDA:SGD | C | endosome |
| GO:0005834 | IDA:SGD | C | heterotrimeric G-protein complex |
| GO:0005886 | IDA:SGD | C | plasma membrane |
| GO:0003924 | IDA:SGD | F | GTPase activity |
| GO:0005525 | IEA:UniProtKB-KW | F | GTP binding |
| GO:0046872 | IEA:UniProtKB-KW | F | metal ion binding |
| GO:0004871 | IEA:UniProtKB-KW | F | signal transducer activity |
| GO:0000754 | IMP:SGD | P | adaptation of signaling pathway by response to pheromone involved in conjugation with cellular fusion |
| GO:0007189 | IEA:InterPro | P | adenylate cyclase-activating G-protein coupled receptor signaling pathway |
| GO:0031684 | IMP:SGD | P | heterotrimeric G-protein complex cycle |
| GO:0048017 | IMP:SGD | P | inositol lipid-mediated signaling |
| GO:0000742 | IMP:SGD | P | karyogamy involved in conjugation with cellular fusion |
| GO:0000743 | IMP:SGD | P | nuclear migration involved in conjugation with cellular fusion |
| GO:0000750 | IMP:SGD | P | pheromone-dependent signal transduction involved in conjugation with cellular fusion |
| GO:0071701 | IMP:SGD | P | regulation of MAPK export from nucleus |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| sce04011 | MAPK signaling pathway - yeast |
REACTOME Pathway Links
Domain Information
UniProt Annotations
Entry Information
Gene Name
guanine nucleotide-binding protein subunit alpha
Protein Entry
GPA1_YEAST
UniProt ID
Species
Yeast (S288c)
Comments
| Comment Type | Description |
|---|---|
| Domain | Contains an 'insertion' sequence of 109 residues which is not present in other G-protein alpha chains. |
| Enzyme Regulation | 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). {ECO:0000269|PubMed:16467474}. |
| Function | 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. {ECO:0000269|PubMed:10356642, ECO:0000269|PubMed:12029138, ECO:0000269|PubMed:12556475, ECO:0000269|PubMed:12960402, ECO:0000269|PubMed:14536090, ECO:0000269|PubMed:15519996, ECO:0000269|PubMed:16839886, ECO:0000269|PubMed:1900495, ECO:0000269|PubMed:2105453, ECO:0000269|PubMed:2107073, ECO:0000269|PubMed:2117698, ECO:0000269|PubMed:2161538, ECO:0000269|PubMed:2494429, ECO:0000269|PubMed:2548076, ECO:0000269|PubMed:2644047, ECO:0000269|PubMed:3113738, ECO:0000269|PubMed:3136318, ECO:0000269|PubMed:8231812, ECO:0000269|PubMed:8887662, ECO:0000269|PubMed:9537998}. |
| Interaction | P11972:SST2; NbExp=3; IntAct=EBI-7376, EBI-18232; P18851:STE4; NbExp=8; IntAct=EBI-7376, EBI-7390; P22219:VPS15; NbExp=2; IntAct=EBI-7376, EBI-20347; P22543:VPS34; NbExp=3; IntAct=EBI-7376, EBI-20405; |
| Miscellaneous | Present with 9920 molecules/cell in log phase SD medium. {ECO:0000269|PubMed:14562106}. |
| Ptm | 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. {ECO:0000269|PubMed:11955054}. |
| Ptm | 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. {ECO:0000269|PubMed:10712512, ECO:0000269|PubMed:1936988, ECO:0000269|PubMed:8415763, ECO:0000269|PubMed:8702760, ECO:0000269|PubMed:8942643}. |
| Similarity | Belongs to the G-alpha family. G(q) subfamily. {ECO:0000305}. |
| Subcellular Location | Cell membrane; Lipid-anchor; Cytoplasmic side. Endosome membrane; Lipid-anchor; Cytoplasmic side. Note=Localizes predominantly to the plasma membrane in its inactive, GDP-bound form, and is directed to endosomes once in its active, GTP-bound form. Concentrates at the tip of the mating projections. |
| Subunit | 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. {ECO:0000269|PubMed:12029138, ECO:0000269|PubMed:14536090, ECO:0000269|PubMed:16467474, ECO:0000269|PubMed:16839886, ECO:0000269|PubMed:8417317, ECO:0000269|PubMed:8756677, ECO:0000269|PubMed:9537998}. |
Identical and Related Proteins
Unique RefSeq proteins for LMP007411 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 6321792 | RefSeq | NP_011868 | 472 | guanine nucleotide-binding protein subunit alpha |
Identical Sequences to LMP007411 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:6321792 | GenBank | AAA34650.1 | 472 | guanine nucleotide-binding protein 1-alpha [Saccharomyces cerevisiae] |
| GI:6321792 | GenBank | AAB68432.1 | 472 | Gpa1p: Alpha subunit of trimeric guanine nucleotide binding protein [Saccharomyces cerevisiae] |
| GI:6321792 | GenBank | AAT92982.1 | 472 | YHR005C [Saccharomyces cerevisiae] |
| GI:6321792 | GenBank | ABC17008.1 | 472 | Sequence 128 from patent US 6949356 |
| GI:6321792 | GenBank | ABZ48083.1 | 472 | Sequence 22021 from patent US 7314974 |
| GI:6321792 | Third Party Genbank | DAA06692.1 | 472 | TPA: guanine nucleotide-binding protein subunit alpha [Saccharomyces cerevisiae S288c] |
Related Sequences to LMP007411 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:6321792 | GenBank | EDV09054.1 | 472 | G protein alpha subunit [Saccharomyces cerevisiae RM11-1a] |
| GI:6321792 | GenBank | EGA74721.1 | 472 | Gpa1p [Saccharomyces cerevisiae AWRI796] |
| GI:6321792 | GenBank | EGA86602.1 | 472 | Gpa1p [Saccharomyces cerevisiae VL3] |
| GI:6321792 | GenBank | EWG90590.1 | 472 | Gpa1p [Saccharomyces cerevisiae P301] |
| GI:6321792 | GenBank | EWG95622.1 | 472 | Gpa1p [Saccharomyces cerevisiae R103] |
| GI:6321792 | GenBank | EWH18042.1 | 472 | Gpa1p [Saccharomyces cerevisiae P283] |