Reviewed, UniProtKB/Swiss-Prot P08539 (GPA1_YEAST)

Names and origin

Protein names

Recommended name:
    Guanine nucleotide-binding protein alpha-1 subunit
Alternative name(s):
    GP1-alpha

Gene names

Name:	GPA1
Synonyms:	CDC70, DAC1, SCG1
Ordered Locus Names:	YHR005C

Organism

Saccharomyces cerevisiae (Baker's yeast) [Complete proteome]

Taxonomic identifier

4932 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	472 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

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. Ref.2 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.17 Ref.22 Ref.23 Ref.27 Ref.34 Ref.35 Ref.36 Ref.39 Ref.43 Ref.44
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). Ref.45
Subunit structure	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 unliganded receptors STE2 and STE3. Interacts with FUS3. Pheromone-induced actvation 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. Ref.23 Ref.34 Ref.35 Ref.44 Ref.45 Ref.16 Ref.21
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. Ref.12 Ref.34 Ref.44 Ref.20 Ref.37
Domain	Contains an 'insertion' sequence of 109 residues which is not present in other G-protein alpha chains.
Post-translational modification	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. Ref.19 Ref.28 Ref.33 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.
Miscellaneous	Present with 9920 molecules/cell in log phase SD medium. Ref.38
Sequence similarities	Belongs to the G-alpha family. G(q) subfamily.

Ontologies

Keywords
Biological process	Pheromone response
Cellular component	Cell membrane Endosome Membrane
Ligand	GTP-binding Nucleotide-binding
Molecular function	Transducer
PTM	Isopeptide bond Lipoprotein Myristate Palmitate Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	adaptation to pheromone during conjugation with cellular fusion Ref.10 Ref.36 Inferred from mutant phenotype. Source: SGD heterotrimeric G-protein complex cycle Ref.9 Inferred from mutant phenotype. Source: SGD inositol lipid-mediated signaling Ref.44 Inferred from mutant phenotype. Source: SGD nuclear migration during conjugation with cellular fusion Inferred from mutant phenotype. Source: SGD pheromone-dependent signal transduction involved in conjugation with cellular fusion Inferred from mutant phenotype. Source: SGD response to drug Inferred from mutant phenotype. Source: SGD
Cellular component	endosome Ref.44 Inferred from direct assay. Source: SGD heterotrimeric G-protein complex Ref.10 Ref.31 Inferred from direct assay. Source: SGD
Molecular function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Ref.14 Ref.31 Inferred from direct assay. Source: SGD protein binding Ref.21 Ref.44 Inferred from physical interaction. Source: IntAct signal transducer activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GPA2	P10823	1	EBI-7376,EBI-7382
SST2	P11972	2	EBI-7376,EBI-18232
STE4	P18851	5	EBI-7376,EBI-7390
VPS15	P22219	2	EBI-7376,EBI-20347
VPS34	P22543	2	EBI-7376,EBI-20405

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 472

471

Guanine nucleotide-binding protein alpha-1 subunit

PRO_0000203616

Regions

Nucleotide binding

48 – 55

8

GTP By similarity

Nucleotide binding

319 – 323

5

GTP By similarity

Nucleotide binding

388 – 391

4

GTP By similarity

Region

127 – 235

109

Insert; not present in other G-proteins

Amino acid modifications

Modified residue

189

1

Phosphothreonine Ref.46

Modified residue

200

1

Phosphoserine Ref.46 Ref.47

Lipidation

2

1

N-myristoyl glycine

Lipidation

3

1

S-palmitoyl cysteine Ref.19 Ref.28 Ref.33

Cross-link

165

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.32

Experimental info

Mutagenesis

2

1

G → A: Abolishes both palmitoylation and N-myristoylation. Ref.34 Ref.20 Ref.19 Ref.28

Mutagenesis

3

1

C → A: Abolishes palmitoylation but not N-myristoylation. Ref.34 Ref.19 Ref.28

Mutagenesis

15

1

D → V: Slightly reduces ligand-dependent pheromone signaling. Ref.34 Ref.42

Mutagenesis

17

1

F → L: Leads to a hypersensitive signaling phenotype resulting in greatly enhanced signal at low alpha-factor concentrations. Ref.34 Ref.42

Mutagenesis

18

1

L → P or Q: Reduces ligand-dependent pheromone signaling. Ref.34 Ref.42

Mutagenesis

21 – 22

2

KR → EE: Impairs interaction with FUS3. Ref.34

Mutagenesis

50

1

G → D: Confers insensitivity to pheromone. Ref.8 Ref.11 Ref.14 Ref.34 Ref.30

Mutagenesis

50

1

G → V: Has increased GTP occupancy and moderately reduces hydrolysis of GTP, resulting in a constitutively active form that downregulates the pheromone response and causes hyperadaptation to pheromone. Ref.8 Ref.11 Ref.14 Ref.34 Ref.30

Mutagenesis

54

1

K → E or I: Prevents GDP to GTP exchange; suppressor of L-323. Ref.34 Ref.42 Ref.25

Mutagenesis

165

1

K → R: Substantial decrease in ubiquitination. Ref.34 Ref.32

Mutagenesis

297

1

R → H: Slows hydrolysis of GTP. Ref.34

Mutagenesis

302

1

G → S in GPA1(SST); weakens interaction to SST2 and blocks its negative regulatory effect. Ref.34 Ref.24

Mutagenesis

321

1

G → T: Causes a specific mating defect in alpha cells. Ref.34 Ref.26

Mutagenesis

322

1

G → A, E or R: Confers insensitivity to pheromone. Ref.11 Ref.14 Ref.22 Ref.34

Mutagenesis

323

1

Q → L: Prevents hydrolysis of GTP; eliminates the interaction with STE4 and constitutively activates the pheromone response pathway. Ref.34 Ref.26

Mutagenesis

327

1

R → S: Suppressor of L-323; does not prevent GTP binding to GPA1. Ref.34 Ref.25

Mutagenesis

345

1

A → T: Suppressor of a STE2-L236H mutant. Ref.34 Ref.29

Mutagenesis

353

1

Missing: Suppressor of L-323. Ref.34 Ref.25

Mutagenesis

355

1

E → K: Confers insensitivity to pheromone. Ref.11 Ref.34

Mutagenesis

364

1

E → K: Enhances the rate of GDP for GTP exchange and slows hydrolysis of GTP, resulting in a constitutively active form that downregulates the pheromone response independently of the pheromone receptor. Ref.11 Ref.22 Ref.34 Ref.31

Mutagenesis

388

1

N → D: Forms a nondissociable complex with the pheromone receptor in response to receptor activation, resulting in reduced pheromone responsiveness. Ref.14 Ref.22 Ref.34 Ref.31 Ref.40

Mutagenesis

388

1

N → K: Causes constitutive activation of the pheromone response pathway. Ref.14 Ref.22 Ref.34 Ref.31 Ref.40

Mutagenesis

391

1

D → A: Causes constitutive activation of the pheromone response pathway. Ref.14 Ref.34

Mutagenesis

467

1

K → P: Impairs pheromone signaling in a and alpha cells. Ref.34 Ref.13

Mutagenesis

468

1

K → P: Impairs pheromone signaling specifically in a cells. Ref.34 Ref.13

Mutagenesis

470

1

G → D: Confers insensitivity to pheromone. Ref.11 Ref.34

Sequence conflict

82

1

W → R in AAA18403. Ref.2

Sequence conflict

194

1

A → V in AAA18403. Ref.2

Sequence conflict

226

1

R → K in AAA18403. Ref.2

Sequence conflict

246

1

K → R in AAA18403. Ref.2

Sequence conflict

469

1

I → S in AAA18403. Ref.2

Secondary structure

1

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472

Helix Strand Turn

Details...

Helix

23 – 38

16

Turn

39 – 40

2

Beta strand

41 – 47

7

Turn

50 – 51

2

Helix

54 – 64

11

Helix

71 – 75

5

Turn

76 – 77

2

Helix

78 – 99

22

Turn

100

1

Turn

216 – 217

2

Helix

218 – 228

11

Beta strand

231 – 233

3

Helix

239 – 249

11

Turn

250 – 251

2

Helix

254 – 260

7

Turn

261 – 263

3

Turn

269 – 270

2

Helix

271 – 276

6

Turn

277

1

Helix

278 – 282

5

Turn

284 – 285

2

Helix

290 – 295

6

Beta strand

304 – 310

7

Turn

311 – 312

2

Beta strand

313 – 319

7

Turn

327 – 330

4

Helix

332 – 334

3

Beta strand

338 – 346

9

Helix

347 – 350

4

Turn

354 – 356

3

Helix

361 – 373

13

Turn

374

1

Helix

376 – 378

3

Turn

379 – 380

2

Beta strand

383 – 388

6

Helix

390 – 399

10

Helix

402 – 404

3

Turn

405

1

Turn

407 – 408

2

Helix

415 – 419

5

Turn

420 – 423

4

Helix

424 – 429

6

Turn

430

1

Beta strand

433 – 435

3

Turn

444 – 445

2

Helix

447 – 464

18

Sequences

	Sequence		Length	Mass (Da)
	P08539-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 2E87C546E133D6E5	FASTA	472	54,076
	10 20 30 40 50 60 MGCTVSTQTI GDESDPFLQN KRANDVIEQS LQLEKQRDKN EIKLLLLGAG ESGKSTVLKQ 70 80 90 100 110 120 LKLLHQGGFS HQERLQYAQV IWADAIQSMK ILIIQARKLG IQLDCDDPIN NKDLFACKRI 130 140 150 160 170 180 LLKAKALDYI NASVAGGSDF LNDYVLKYSE RYETRRRVQS TGRAKAAFDE DGNISNVKSD 190 200 210 220 230 240 TDRDAETVTQ NEDADRNNSS RINLQDICKD LNQEGDDQMF VRKTSREIQG QNRRNLIHED 250 260 270 280 290 300 IAKAIKQLWN NDKGIKQCFA RSNEFQLEGS AAYYFDNIEK FASPNYVCTD EDILKGRIKT 310 320 330 340 350 360 TGITETEFNI GSSKFKVLDA GGQRSERKKW IHCFEGITAV LFVLAMSEYD QMLFEDERVN 370 380 390 400 410 420 RMHESIMLFD TLLNSKWFKD TPFILFLNKI DLFEEKVKSM PIRKYFPDYQ GRVGDAEAGL 430 440 450 460 470 KYFEKIFLSL NKTNKPIYVK RTCATDTQTM KFVLSAVTDL IIQQNLKKIG II

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Occurrence in Saccharomyces cerevisiae of a gene homologous to the cDNA coding for the alpha subunit of mammalian G proteins." Nakafuku M., Itoh H., Nakamura S., Kaziro Y. Proc. Natl. Acad. Sci. U.S.A. 84:2140-2144(1987) [PubMed: 3031665] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The yeast SCG1 gene: a G alpha-like protein implicated in the a- and alpha-factor response pathway." Dietzel C., Kurjan J. Cell 50:1001-1010(1987) [PubMed: 3113738] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION.
[3]	"Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII." Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z., Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T., Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P. , Louis E.J., Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L., St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P., Waterston R., Wilson R., Vaudin M. Science 265:2077-2082(1994) [PubMed: 8091229] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[4]	"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J. Genome Res. 17:536-543(2007) [PubMed: 17322287] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[5]	"Mutations in a gene encoding the alpha subunit of a Saccharomyces cerevisiae G protein indicate a role in mating pheromone signaling." Jahng K.-Y., Ferguson J., Reed S.I. Mol. Cell. Biol. 8:2484-2493(1988) [PubMed: 3136318] [Abstract] Cited for: FUNCTION.
[6]	"Constitutive mutants in the yeast pheromone response: ordered function of the gene products." Blinder D., Bouvier S., Jenness D.D. Cell 56:479-486(1989) [PubMed: 2644047] [Abstract] Cited for: FUNCTION.
[7]	"The yeast G-protein homolog is involved in the mating pheromone signal transduction system." Fujimura H.A. Mol. Cell. Biol. 9:152-158(1989) [PubMed: 2494429] [Abstract] Cited for: FUNCTION.
[8]	"GPA1Val-50 mutation in the mating-factor signaling pathway in Saccharomyces cerevisiae." Miyajima I., Arai K., Matsumoto K. Mol. Cell. Biol. 9:2289-2297(1989) [PubMed: 2548076] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLY-50.
[9]	"Regulation of the yeast pheromone response pathway by G protein subunits." Nomoto S., Nakayama N., Arai K., Matsumoto K. EMBO J. 9:691-696(1990) [PubMed: 2107073] [Abstract] Cited for: FUNCTION.
[10]	"Stoichiometry of G protein subunits affects the Saccharomyces cerevisiae mating pheromone signal transduction pathway." Cole G.M., Stone D.E., Reed S.I. Mol. Cell. Biol. 10:510-517(1990) [PubMed: 2105453] [Abstract] Cited for: FUNCTION.
[11]	"G protein mutations that alter the pheromone response in Saccharomyces cerevisiae." Stone D.E., Reed S.I. Mol. Cell. Biol. 10:4439-4446(1990) [PubMed: 2117698] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLY-50; GLY-322; GLU-355; GLU-364 AND GLY-470.
[12]	"Beta and gamma subunits of a yeast guanine nucleotide-binding protein are not essential for membrane association of the alpha subunit but are required for receptor coupling." Blumer K.J., Thorner J. Proc. Natl. Acad. Sci. U.S.A. 87:4363-4367(1990) [PubMed: 2161538] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[13]	"The carboxyl terminus of Scg1, the G alpha subunit involved in yeast mating, is implicated in interactions with the pheromone receptors." Hirsch J.P., Dietzel C., Kurjan J. Genes Dev. 5:467-474(1991) [PubMed: 1848203] [Abstract] Cited for: MUTAGENESIS OF LYS-467 AND LYS-468.
[14]	"Mutations in the guanine nucleotide-binding domains of a yeast G alpha protein confer a constitutive or uninducible state to the pheromone response pathway." Kurjan J., Hirsch J.P., Dietzel C. Genes Dev. 5:475-483(1991) [PubMed: 1900495] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLY-50; GLY-322; ASN-388 AND ASP-391.
[15]	"N-myristoylation is required for function of the pheromone-responsive G alpha protein of yeast: conditional activation of the pheromone response by a temperature-sensitive N-myristoyl transferase." Stone D.E., Cole G.M., de Barros Lopes M., Goebl M., Reed S.I. Genes Dev. 5:1969-1981(1991) [PubMed: 1936988] [Abstract] Cited for: MYRISTOYLATION AT GLY-2.
[16]	"Interactions among the subunits of the G protein involved in Saccharomyces cerevisiae mating." Clark K.L., Dignard D., Thomas D.Y., Whiteway M. Mol. Cell. Biol. 13:1-8(1993) [PubMed: 8417317] [Abstract] Cited for: INTERACTION WITH STE4.
[17]	"Suppression of a dominant G-protein beta-subunit mutation in yeast by G alpha protein expression." Zhang M., Tipper D.J. Mol. Microbiol. 9:813-821(1993) [PubMed: 8231812] [Abstract] Cited for: FUNCTION.
[18]	"Pheromone action regulates G-protein alpha-subunit myristoylation in the yeast Saccharomyces cerevisiae." Dohlman H.G., Goldsmith P., Spiegel A.M., Thorner J. Proc. Natl. Acad. Sci. U.S.A. 90:9688-9692(1993) [PubMed: 8415763] [Abstract] Cited for: MYRISTOYLATION AT GLY-2.
[19]	"Partial constitutive activation of pheromone responses by a palmitoylation-site mutant of a G protein alpha subunit in yeast." Song J., Dohlman H.G. Biochemistry 35:14806-14817(1996) [PubMed: 8942643] [Abstract] Cited for: PALMITOYLATION AT CYS-3, MUTAGENESIS OF GLY-2 AND CYS-3.
[20]	"Regulation of membrane and subunit interactions by N-myristoylation of a G protein alpha subunit in yeast." Song J., Hirschman J., Gunn K., Dohlman H.G. J. Biol. Chem. 271:20273-20283(1996) [PubMed: 8702760] [Abstract] Cited for: MYRISTOYLATION AT GLY-2, MUTAGENESIS OF GLY-2, SUBCELLULAR LOCATION.
[21]	"Sst2, a negative regulator of pheromone signaling in the yeast Saccharomyces cerevisiae: Expression, localization, and genetic interaction and physical association with Gpa1 (the G-protein alpha subunit)." Dohlman H.G., Song J., Ma D., Courchesne W.E., Thorner J. Mol. Cell. Biol. 16:5194-5209(1996) [PubMed: 8756677] [Abstract] Cited for: INTERACTION WITH SST2.
[22]	"The mating-specific G(alpha) protein of Saccharomyces cerevisiae downregulates the mating signal by a mechanism that is dependent on pheromone and independent of G(beta)(gamma) sequestration." Stratton H.F., Zhou J., Reed S.I., Stone D.E. Mol. Cell. Biol. 16:6325-6337(1996) [PubMed: 8887662] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLY-322; GLU-364 AND ASN-388.
[23]	"Sst2 is a GTPase-activating protein for Gpa1: purification and characterization of a cognate RGS-Galpha protein pair in yeast." Apanovitch D.M., Slep K.C., Sigler P.B., Dohlman H.G. Biochemistry 37:4815-4822(1998) [PubMed: 9537998] [Abstract] Cited for: FUNCTION, INTERACTION WITH SST2.
[24]	"Selective uncoupling of RGS action by a single point mutation in the G protein alpha-subunit." DiBello P.R., Garrison T.R., Apanovitch D.M., Hoffman G., Shuey D.J., Mason K., Cockett M.I., Dohlman H.G. J. Biol. Chem. 273:5780-5784(1998) [PubMed: 9488712] [Abstract] Cited for: MUTAGENESIS OF GLY-302.
[25]	"Second site suppressor mutations of a GTPase-deficient G-protein alpha-subunit." Apanovitch D.M., Iiri T., Karasawa T., Bourne H.R., Dohlman H.G. J. Biol. Chem. 273:28597-28602(1998) [PubMed: 9786851] [Abstract] Cited for: MUTAGENESIS OF LYS-54; ARG-327 AND LEU-353.
[26]	"Switch-domain mutations in the Saccharomyces cerevisiae G protein alpha-subunit Gpa1p identify a receptor subtype-biased mating defect." DeSimone S.M., Kurjan J. Mol. Gen. Genet. 257:662-671(1998) [PubMed: 9604890] [Abstract] Cited for: MUTAGENESIS OF GLY-321 AND GLN-323.
[27]	"The yeast pheromone-responsive G alpha protein stimulates recovery from chronic pheromone treatment by two mechanisms that are activated at distinct levels of stimulus." Zhou J., Arora M., Stone D.E. Cell Biochem. Biophys. 30:193-212(1999) [PubMed: 10356642] [Abstract] Cited for: FUNCTION.
[28]	"Dual lipid modification motifs in G(alpha) and G(gamma) subunits are required for full activity of the pheromone response pathway in Saccharomyces cerevisiae." Manahan C.L., Patnana M., Blumer K.J., Linder M.E. Mol. Biol. Cell 11:957-968(2000) [PubMed: 10712512] [Abstract] Cited for: PALMITOYLATION AT CYS-3, MUTAGENESIS OF GLY-2 AND CYS-3.
[29]	"The C terminus of the Saccharomyces cerevisiae alpha-factor receptor contributes to the formation of preactivation complexes with its cognate G protein." Dosil M., Schandel K.A., Gupta E., Jenness D.D., Konopka J.B. Mol. Cell. Biol. 20:5321-5329(2000) [PubMed: 10866688] [Abstract] Cited for: MUTAGENESIS OF ALA-345, FORMATION OF PREACTIVATION COMPLEXES.
[30]	"The GTP hydrolysis defect of the Saccharomyces cerevisiae mutant G-protein Gpa1(G50V)." Kallal L., Fishel R. Yeast 16:387-400(2000) [PubMed: 10705368] [Abstract] Cited for: MUTAGENESIS OF GLY-50.
[31]	"Biochemical analysis of yeast G(alpha) mutants that enhance adaptation to pheromone." Cismowski M.J., Metodiev M.V., Draper E., Stone D.E. Biochem. Biophys. Res. Commun. 284:247-254(2001) [PubMed: 11394869] [Abstract] Cited for: MUTAGENESIS OF GLU-364 AND ASN-388.
[32]	"Direct identification of a G protein ubiquitination site by mass spectrometry." Marotti L.A. Jr., Newitt R., Wang Y., Aebersold R., Dohlman H.G. Biochemistry 41:5067-5074(2002) [PubMed: 11955054] [Abstract] Cited for: UBIQUITINATION AT LYS-165, MUTAGENESIS OF LYS-165, MASS SPECTROMETRY.
[33]	"Characterization of Saccharomyces cerevisiae acyl-protein thioesterase 1, the enzyme responsible for G protein alpha subunit deacylation in vivo." Duncan J.A., Gilman A.G. J. Biol. Chem. 277:31740-31752(2002) [PubMed: 12080046] [Abstract] Cited for: DEPALMITOYLATION.
[34]	"Regulation of MAPK function by direct interaction with the mating-specific G(alpha) in yeast." Metodiev M.V., Matheos D., Rose M.D., Stone D.E. Science 296:1483-1486(2002) [PubMed: 12029138] [Abstract] Cited for: FUNCTION, INTERACTION WITH FUS3, MUTAGENESIS OF 21-LSY-ARG-22, SUBCELLULAR LOCATION.
[35]	"The yeast G protein alpha subunit Gpa1 transmits a signal through an RNA binding effector protein Scp160." Guo M., Aston C., Burchett S.A., Dyke C., Fields S., Rajarao S.J.R., Uetz P., Wang Y., Young K., Dohlman H.G. Mol. Cell 12:517-524(2003) [PubMed: 14536090] [Abstract] Cited for: FUNCTION, INTERACTION WITH SCP160.
[36]	"Effect of the pheromone-responsive G(alpha) and phosphatase proteins of Saccharomyces cerevisiae on the subcellular localization of the Fus3 mitogen-activated protein kinase." Blackwell E., Halatek I.M., Kim H.-J.N., Ellicott A.T., Obukhov A.A., Stone D.E. Mol. Cell. Biol. 23:1135-1150(2003) [PubMed: 12556475] [Abstract] Cited for: FUNCTION.
[37]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed: 14562095] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[38]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[39]	"A quantitative characterization of the yeast heterotrimeric G protein cycle." Yi T.-M., Kitano H., Simon M.I. Proc. Natl. Acad. Sci. U.S.A. 100:10764-10769(2003) [PubMed: 12960402] [Abstract] Cited for: FUNCTION.
[40]	"Dominant-negative inhibition of pheromone receptor signaling by a single point mutation in the G protein alpha subunit." Wu Y.-L., Hooks S.B., Harden T.K., Dohlman H.G. J. Biol. Chem. 279:35287-35297(2004) [PubMed: 15197187] [Abstract] Cited for: MUTAGENESIS OF ASN-388.
[41]	Erratum Wu Y.-L., Hooks S.B., Harden T.K., Dohlman H.G. J. Biol. Chem. 280:29988-29988(2005)
[42]	"Effects of mutations in the N terminal region of the yeast G protein alpha-subunit Gpa1p on signaling by pheromone receptors." Roginskaya M., Connelly S.M., Kim K.S., Patel D., Dumont M.E. Mol. Genet. Genomics 271:237-248(2004) [PubMed: 14767760] [Abstract] Cited for: MUTAGENESIS OF ASP-15; PHE-17; LEU-18 AND LYS-54.
[43]	"Differential regulation of G protein alpha subunit trafficking by mono-and polyubiquitination." Wang Y., Marotti L.A. Jr., Lee M.J., Dohlman H.G. J. Biol. Chem. 280:284-291(2005) [PubMed: 15519996] [Abstract] Cited for: FUNCTION OF UBIQUITINATION.
[44]	"Activation of the phosphatidylinositol 3-kinase Vps34 by a G protein alpha subunit at the endosome." Slessareva J.E., Routt S.M., Temple B., Bankaitis V.A., Dohlman H.G. Cell 126:191-203(2006) [PubMed: 16839886] [Abstract] Cited for: FUNCTION, INTERACTION WITH VPS15 AND VPS34, SUBCELLULAR LOCATION.
[45]	"Genome-scale analysis reveals Sst2 as the principal regulator of mating pheromone signaling in the yeast Saccharomyces cerevisiae." Chasse S.A., Flanary P., Parnell S.C., Hao N., Cha J.Y., Siderovski D.P., Dohlman H.G. Eukaryot. Cell 5:330-346(2006) [PubMed: 16467474] [Abstract] Cited for: INTERACTION WITH MDM1; RAX1; RGS2 AND SST2, ENZYME REGULATION.
[46]	"Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Smolka M.B., Albuquerque C.P., Chen S.H., Zhou H. Proc. Natl. Acad. Sci. U.S.A. 104:10364-10369(2007) [PubMed: 17563356] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-189 AND SER-200, MASS SPECTROMETRY.
[47]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200, MASS SPECTROMETRY.
[48]	Gaitatzes C.G., Neer E.J., Smith T.F. Submitted (FEB-1998) to the PDB data bank Cited for: 3D-STRUCTURE MODELING.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M15867 Genomic DNA. Translation: AAA34650.1.
M17414 Unassigned DNA. Translation: AAA18403.1.
U10555 Genomic DNA. Translation: AAB68432.1.
AY692963 Genomic DNA. Translation: AAT92982.1.

PIR

A25906.

RefSeq

NP_011868.1.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1SCG	model	-	A	1-472	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:15N.

IntAct

P08539. 19 interactions.

STRING

P08539.

Proteomic databases

PeptideAtlas

P08539.

Genome annotation databases

Ensembl

YHR005C; YHR005C; YHR005C; Saccharomyces cerevisiae. [Genome view]

GeneID

856394.

KEGG

sce:YHR005C.

NMPDR

fig|4932.3.peg.3012.

Organism-specific databases

CYGD

YHR005c.

SGD

S000001047. GPA1.

Phylogenomic databases

HOGENOM

P08539.

OMA

DERESFK

OrthoDB

EOG9JHDZC

Gene expression databases

ArrayExpress

P08539.

Genevestigator

P08539.

GermOnline

YHR005C. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR002975. Fungi_GproteinA.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
[Graphical view]

PANTHER

PTHR10218. Gprotein_alph_bd. 1 hit.

Pfam

PF00503. G-alpha. 1 hit.
[Graphical view]

PRINTS

PR00318. GPROTEINA.
PR01241. GPROTEINAFNG.

SMART

SM00275. G_alpha. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

981914.

Entry information

Entry name

GPA1_YEAST

Accession

Primary (citable) accession number: P08539

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	November 24, 2009
This is version 116 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)