GPA1_YEAST
ID GPA1_YEAST Reviewed; 472 AA.
AC P08539; D3DKU8;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Guanine nucleotide-binding protein alpha-1 subunit;
DE AltName: Full=GP1-alpha;
GN Name=GPA1; Synonyms=CDC70, DAC1, SCG1; OrderedLocusNames=YHR005C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3031665; DOI=10.1073/pnas.84.8.2140;
RA Nakafuku M., Itoh H., Nakamura S., Kaziro Y.;
RT "Occurrence in Saccharomyces cerevisiae of a gene homologous to the cDNA
RT coding for the alpha subunit of mammalian G proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:2140-2144(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=3113738; DOI=10.1016/0092-8674(87)90166-8;
RA Dietzel C., Kurjan J.;
RT "The yeast SCG1 gene: a G alpha-like protein implicated in the a- and
RT alpha-factor response pathway.";
RL Cell 50:1001-1010(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8091229; DOI=10.1126/science.8091229;
RA Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z.,
RA Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T.,
RA Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P., Louis E.J.,
RA Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L.,
RA St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P.,
RA Waterston R., Wilson R., Vaudin M.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome
RT VIII.";
RL Science 265:2077-2082(1994).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [6]
RP FUNCTION.
RX PubMed=3136318; DOI=10.1128/mcb.8.6.2484-2493.1988;
RA Jahng K.-Y., Ferguson J., Reed S.I.;
RT "Mutations in a gene encoding the alpha subunit of a Saccharomyces
RT cerevisiae G protein indicate a role in mating pheromone signaling.";
RL Mol. Cell. Biol. 8:2484-2493(1988).
RN [7]
RP FUNCTION.
RX PubMed=2644047; DOI=10.1016/0092-8674(89)90250-x;
RA Blinder D., Bouvier S., Jenness D.D.;
RT "Constitutive mutants in the yeast pheromone response: ordered function of
RT the gene products.";
RL Cell 56:479-486(1989).
RN [8]
RP FUNCTION.
RX PubMed=2494429; DOI=10.1128/mcb.9.1.152-158.1989;
RA Fujimura H.A.;
RT "The yeast G-protein homolog is involved in the mating pheromone signal
RT transduction system.";
RL Mol. Cell. Biol. 9:152-158(1989).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF GLY-50.
RX PubMed=2548076; DOI=10.1128/mcb.9.6.2289-2297.1989;
RA Miyajima I., Arai K., Matsumoto K.;
RT "GPA1Val-50 mutation in the mating-factor signaling pathway in
RT Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 9:2289-2297(1989).
RN [10]
RP FUNCTION.
RX PubMed=2107073; DOI=10.1002/j.1460-2075.1990.tb08161.x;
RA Nomoto S., Nakayama N., Arai K., Matsumoto K.;
RT "Regulation of the yeast pheromone response pathway by G protein
RT subunits.";
RL EMBO J. 9:691-696(1990).
RN [11]
RP FUNCTION.
RX PubMed=2105453; DOI=10.1128/mcb.10.2.510-517.1990;
RA Cole G.M., Stone D.E., Reed S.I.;
RT "Stoichiometry of G protein subunits affects the Saccharomyces cerevisiae
RT mating pheromone signal transduction pathway.";
RL Mol. Cell. Biol. 10:510-517(1990).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF GLY-50; GLY-322; GLU-355; GLU-364 AND GLY-470.
RX PubMed=2117698; DOI=10.1128/mcb.10.9.4439-4446.1990;
RA Stone D.E., Reed S.I.;
RT "G protein mutations that alter the pheromone response in Saccharomyces
RT cerevisiae.";
RL Mol. Cell. Biol. 10:4439-4446(1990).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=2161538; DOI=10.1073/pnas.87.11.4363;
RA Blumer K.J., Thorner J.;
RT "Beta and gamma subunits of a yeast guanine nucleotide-binding protein are
RT not essential for membrane association of the alpha subunit but are
RT required for receptor coupling.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:4363-4367(1990).
RN [14]
RP MUTAGENESIS OF LYS-467 AND LYS-468.
RX PubMed=1848203; DOI=10.1101/gad.5.3.467;
RA Hirsch J.P., Dietzel C., Kurjan J.;
RT "The carboxyl terminus of Scg1, the G alpha subunit involved in yeast
RT mating, is implicated in interactions with the pheromone receptors.";
RL Genes Dev. 5:467-474(1991).
RN [15]
RP FUNCTION, AND MUTAGENESIS OF GLY-50; GLY-322; ASN-388 AND ASP-391.
RX PubMed=1900495; DOI=10.1101/gad.5.3.475;
RA Kurjan J., Hirsch J.P., Dietzel C.;
RT "Mutations in the guanine nucleotide-binding domains of a yeast G alpha
RT protein confer a constitutive or uninducible state to the pheromone
RT response pathway.";
RL Genes Dev. 5:475-483(1991).
RN [16]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=1936988; DOI=10.1101/gad.5.11.1969;
RA Stone D.E., Cole G.M., de Barros Lopes M., Goebl M., Reed S.I.;
RT "N-myristoylation is required for function of the pheromone-responsive G
RT alpha protein of yeast: conditional activation of the pheromone response by
RT a temperature-sensitive N-myristoyl transferase.";
RL Genes Dev. 5:1969-1981(1991).
RN [17]
RP INTERACTION WITH STE4.
RX PubMed=8417317; DOI=10.1128/mcb.13.1.1-8.1993;
RA Clark K.L., Dignard D., Thomas D.Y., Whiteway M.;
RT "Interactions among the subunits of the G protein involved in Saccharomyces
RT cerevisiae mating.";
RL Mol. Cell. Biol. 13:1-8(1993).
RN [18]
RP FUNCTION.
RX PubMed=8231812; DOI=10.1111/j.1365-2958.1993.tb01740.x;
RA Zhang M., Tipper D.J.;
RT "Suppression of a dominant G-protein beta-subunit mutation in yeast by G
RT alpha protein expression.";
RL Mol. Microbiol. 9:813-821(1993).
RN [19]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=8415763; DOI=10.1073/pnas.90.20.9688;
RA Dohlman H.G., Goldsmith P., Spiegel A.M., Thorner J.;
RT "Pheromone action regulates G-protein alpha-subunit myristoylation in the
RT yeast Saccharomyces cerevisiae.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:9688-9692(1993).
RN [20]
RP PALMITOYLATION AT CYS-3, AND MUTAGENESIS OF GLY-2 AND CYS-3.
RX PubMed=8942643; DOI=10.1021/bi961846b;
RA Song J., Dohlman H.G.;
RT "Partial constitutive activation of pheromone responses by a
RT palmitoylation-site mutant of a G protein alpha subunit in yeast.";
RL Biochemistry 35:14806-14817(1996).
RN [21]
RP MYRISTOYLATION AT GLY-2, MUTAGENESIS OF GLY-2, AND SUBCELLULAR LOCATION.
RX PubMed=8702760; DOI=10.1074/jbc.271.34.20273;
RA Song J., Hirschman J., Gunn K., Dohlman H.G.;
RT "Regulation of membrane and subunit interactions by N-myristoylation of a G
RT protein alpha subunit in yeast.";
RL J. Biol. Chem. 271:20273-20283(1996).
RN [22]
RP INTERACTION WITH SST2.
RX PubMed=8756677; DOI=10.1128/mcb.16.9.5194;
RA Dohlman H.G., Song J., Ma D., Courchesne W.E., Thorner J.;
RT "Sst2, a negative regulator of pheromone signaling in the yeast
RT Saccharomyces cerevisiae: Expression, localization, and genetic interaction
RT and physical association with Gpa1 (the G-protein alpha subunit).";
RL Mol. Cell. Biol. 16:5194-5209(1996).
RN [23]
RP FUNCTION, AND MUTAGENESIS OF GLY-322; GLU-364 AND ASN-388.
RX PubMed=8887662; DOI=10.1128/mcb.16.11.6325;
RA Stratton H.F., Zhou J., Reed S.I., Stone D.E.;
RT "The mating-specific G(alpha) protein of Saccharomyces cerevisiae
RT downregulates the mating signal by a mechanism that is dependent on
RT pheromone and independent of G(beta)(gamma) sequestration.";
RL Mol. Cell. Biol. 16:6325-6337(1996).
RN [24]
RP FUNCTION, AND INTERACTION WITH SST2.
RX PubMed=9537998; DOI=10.1021/bi9729965;
RA Apanovitch D.M., Slep K.C., Sigler P.B., Dohlman H.G.;
RT "Sst2 is a GTPase-activating protein for Gpa1: purification and
RT characterization of a cognate RGS-Galpha protein pair in yeast.";
RL Biochemistry 37:4815-4822(1998).
RN [25]
RP MUTAGENESIS OF GLY-302.
RX PubMed=9488712; DOI=10.1074/jbc.273.10.5780;
RA DiBello P.R., Garrison T.R., Apanovitch D.M., Hoffman G., Shuey D.J.,
RA Mason K., Cockett M.I., Dohlman H.G.;
RT "Selective uncoupling of RGS action by a single point mutation in the G
RT protein alpha-subunit.";
RL J. Biol. Chem. 273:5780-5784(1998).
RN [26]
RP MUTAGENESIS OF LYS-54; ARG-327 AND LEU-353.
RX PubMed=9786851; DOI=10.1074/jbc.273.44.28597;
RA Apanovitch D.M., Iiri T., Karasawa T., Bourne H.R., Dohlman H.G.;
RT "Second site suppressor mutations of a GTPase-deficient G-protein alpha-
RT subunit.";
RL J. Biol. Chem. 273:28597-28602(1998).
RN [27]
RP MUTAGENESIS OF GLY-321 AND GLN-323.
RX PubMed=9604890; DOI=10.1007/s004380050695;
RA DeSimone S.M., Kurjan J.;
RT "Switch-domain mutations in the Saccharomyces cerevisiae G protein alpha-
RT subunit Gpa1p identify a receptor subtype-biased mating defect.";
RL Mol. Gen. Genet. 257:662-671(1998).
RN [28]
RP FUNCTION.
RX PubMed=10356642; DOI=10.1007/bf02738067;
RA Zhou J., Arora M., Stone D.E.;
RT "The yeast pheromone-responsive G alpha protein stimulates recovery from
RT chronic pheromone treatment by two mechanisms that are activated at
RT distinct levels of stimulus.";
RL Cell Biochem. Biophys. 30:193-212(1999).
RN [29]
RP PALMITOYLATION AT CYS-3, AND MUTAGENESIS OF GLY-2 AND CYS-3.
RX PubMed=10712512; DOI=10.1091/mbc.11.3.957;
RA Manahan C.L., Patnana M., Blumer K.J., Linder M.E.;
RT "Dual lipid modification motifs in G(alpha) and G(gamma) subunits are
RT required for full activity of the pheromone response pathway in
RT Saccharomyces cerevisiae.";
RL Mol. Biol. Cell 11:957-968(2000).
RN [30]
RP MUTAGENESIS OF ALA-345, AND FORMATION OF PREACTIVATION COMPLEXES.
RX PubMed=10866688; DOI=10.1128/mcb.20.14.5321-5329.2000;
RA Dosil M., Schandel K.A., Gupta E., Jenness D.D., Konopka J.B.;
RT "The C terminus of the Saccharomyces cerevisiae alpha-factor receptor
RT contributes to the formation of preactivation complexes with its cognate G
RT protein.";
RL Mol. Cell. Biol. 20:5321-5329(2000).
RN [31]
RP MUTAGENESIS OF GLY-50.
RX PubMed=10705368;
RX DOI=10.1002/(sici)1097-0061(20000330)16:5<387::aid-yea525>3.0.co;2-u;
RA Kallal L., Fishel R.;
RT "The GTP hydrolysis defect of the Saccharomyces cerevisiae mutant G-protein
RT Gpa1(G50V).";
RL Yeast 16:387-400(2000).
RN [32]
RP MUTAGENESIS OF GLU-364 AND ASN-388.
RX PubMed=11394869; DOI=10.1006/bbrc.2001.4959;
RA Cismowski M.J., Metodiev M.V., Draper E., Stone D.E.;
RT "Biochemical analysis of yeast G(alpha) mutants that enhance adaptation to
RT pheromone.";
RL Biochem. Biophys. Res. Commun. 284:247-254(2001).
RN [33]
RP UBIQUITINATION AT LYS-165, MUTAGENESIS OF LYS-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=11955054; DOI=10.1021/bi015940q;
RA Marotti L.A. Jr., Newitt R., Wang Y., Aebersold R., Dohlman H.G.;
RT "Direct identification of a G protein ubiquitination site by mass
RT spectrometry.";
RL Biochemistry 41:5067-5074(2002).
RN [34]
RP DEPALMITOYLATION.
RX PubMed=12080046; DOI=10.1074/jbc.m202505200;
RA Duncan J.A., Gilman A.G.;
RT "Characterization of Saccharomyces cerevisiae acyl-protein thioesterase 1,
RT the enzyme responsible for G protein alpha subunit deacylation in vivo.";
RL J. Biol. Chem. 277:31740-31752(2002).
RN [35]
RP FUNCTION, INTERACTION WITH FUS3, MUTAGENESIS OF 21-LYS-ARG-22, AND
RP SUBCELLULAR LOCATION.
RX PubMed=12029138; DOI=10.1126/science.1070540;
RA Metodiev M.V., Matheos D., Rose M.D., Stone D.E.;
RT "Regulation of MAPK function by direct interaction with the mating-specific
RT G(alpha) in yeast.";
RL Science 296:1483-1486(2002).
RN [36]
RP FUNCTION, AND INTERACTION WITH SCP160.
RX PubMed=14536090; DOI=10.1016/s1097-2765(03)00307-1;
RA Guo M., Aston C., Burchett S.A., Dyke C., Fields S., Rajarao S.J.R.,
RA Uetz P., Wang Y., Young K., Dohlman H.G.;
RT "The yeast G protein alpha subunit Gpa1 transmits a signal through an RNA
RT binding effector protein Scp160.";
RL Mol. Cell 12:517-524(2003).
RN [37]
RP FUNCTION.
RX PubMed=12556475; DOI=10.1128/mcb.23.4.1135-1150.2003;
RA Blackwell E., Halatek I.M., Kim H.-J.N., Ellicott A.T., Obukhov A.A.,
RA Stone D.E.;
RT "Effect of the pheromone-responsive G(alpha) and phosphatase proteins of
RT Saccharomyces cerevisiae on the subcellular localization of the Fus3
RT mitogen-activated protein kinase.";
RL Mol. Cell. Biol. 23:1135-1150(2003).
RN [38]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [39]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [40]
RP FUNCTION.
RX PubMed=12960402; DOI=10.1073/pnas.1834247100;
RA Yi T.-M., Kitano H., Simon M.I.;
RT "A quantitative characterization of the yeast heterotrimeric G protein
RT cycle.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:10764-10769(2003).
RN [41]
RP MUTAGENESIS OF ASN-388.
RX PubMed=15197187; DOI=10.1074/jbc.m404896200;
RA Wu Y.-L., Hooks S.B., Harden T.K., Dohlman H.G.;
RT "Dominant-negative inhibition of pheromone receptor signaling by a single
RT point mutation in the G protein alpha subunit.";
RL J. Biol. Chem. 279:35287-35297(2004).
RN [42]
RP ERRATUM OF PUBMED:15197187.
RA Wu Y.-L., Hooks S.B., Harden T.K., Dohlman H.G.;
RL J. Biol. Chem. 280:29988-29988(2005).
RN [43]
RP MUTAGENESIS OF ASP-15; PHE-17; LEU-18 AND LYS-54.
RX PubMed=14767760; DOI=10.1007/s00438-004-0975-y;
RA Roginskaya M., Connelly S.M., Kim K.S., Patel D., Dumont M.E.;
RT "Effects of mutations in the N terminal region of the yeast G protein
RT alpha-subunit Gpa1p on signaling by pheromone receptors.";
RL Mol. Genet. Genomics 271:237-248(2004).
RN [44]
RP FUNCTION OF UBIQUITINATION.
RX PubMed=15519996; DOI=10.1074/jbc.m411624200;
RA Wang Y., Marotti L.A. Jr., Lee M.J., Dohlman H.G.;
RT "Differential regulation of G protein alpha subunit trafficking by
RT mono- and polyubiquitination.";
RL J. Biol. Chem. 280:284-291(2005).
RN [45]
RP FUNCTION, INTERACTION WITH VPS15 AND VPS34, AND SUBCELLULAR LOCATION.
RX PubMed=16839886; DOI=10.1016/j.cell.2006.04.045;
RA Slessareva J.E., Routt S.M., Temple B., Bankaitis V.A., Dohlman H.G.;
RT "Activation of the phosphatidylinositol 3-kinase Vps34 by a G protein alpha
RT subunit at the endosome.";
RL Cell 126:191-203(2006).
RN [46]
RP INTERACTION WITH MDM1; RAX1; RGS2 AND SST2, AND ACTIVITY REGULATION.
RX PubMed=16467474; DOI=10.1128/ec.5.2.330-346.2006;
RA Chasse S.A., Flanary P., Parnell S.C., Hao N., Cha J.Y., Siderovski D.P.,
RA Dohlman H.G.;
RT "Genome-scale analysis reveals Sst2 as the principal regulator of mating
RT pheromone signaling in the yeast Saccharomyces cerevisiae.";
RL Eukaryot. Cell 5:330-346(2006).
RN [47]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [48]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
CC -!- FUNCTION: Alpha subunit of the heterotrimeric guanine nucleotide-
CC binding protein (G protein) that mediates mating pheromone signal
CC transduction. Binding of alpha-factor or a-factor to its cognate
CC transmembrane receptor STE2 and STE3, respectively, allows the receptor
CC to serve as a guanine nucleotide exchange factor (GEF) on GPA1. The
CC exchange of GDP for GTP on the G protein alpha subunit alters its
CC interaction with the G protein beta subunit STE4, leading to
CC dissociation of the G protein beta-gamma dimer STE4-STE18. The
CC dissociated subunits activate downstream effectors to activate the
CC mating response pathway and induce changes necessary to produce mating-
CC competent cells. STE4-STE18 activate the downstream pheromone signaling
CC MAP kinase cascade leading to expression of mating-specific genes,
CC inducing cell cycle arrest in G1, promoting polarized cell growth to
CC form mating projections (shmoos), and establishing the changes in
CC plasma membrane, cell wall and nuclear envelope to permit cell-cell
CC fusion (plasmogamy) and fusion of the two haploid nuclei (karyogamy).
CC GPA1 transmits a signal that requires direct binding to the effector
CC enzyme PI3K located at the endosome, promoting increased PI3
CC production. The intrinsic GTPase activity of GPA1 determines the
CC duration of signaling, and is dramatically accelerated by the RGS
CC protein SST2. In unstimulated cells, GDP-bound GPA1 sequesters the G
CC protein beta-gamma subunit STE4-STE18, preventing it from activating
CC the downstream effectors. Also down-regulates the signal by inhibiting
CC the pheromone-induced accumulation of FUS3 in the nucleus.
CC {ECO:0000269|PubMed:10356642, ECO:0000269|PubMed:12029138,
CC ECO:0000269|PubMed:12556475, ECO:0000269|PubMed:12960402,
CC ECO:0000269|PubMed:14536090, ECO:0000269|PubMed:15519996,
CC ECO:0000269|PubMed:16839886, ECO:0000269|PubMed:1900495,
CC ECO:0000269|PubMed:2105453, ECO:0000269|PubMed:2107073,
CC ECO:0000269|PubMed:2117698, ECO:0000269|PubMed:2161538,
CC ECO:0000269|PubMed:2494429, ECO:0000269|PubMed:2548076,
CC ECO:0000269|PubMed:2644047, ECO:0000269|PubMed:3113738,
CC ECO:0000269|PubMed:3136318, ECO:0000269|PubMed:8231812,
CC ECO:0000269|PubMed:8887662, ECO:0000269|PubMed:9537998}.
CC -!- ACTIVITY REGULATION: Alternates between an inactive form bound to GDP
CC and an active form bound to GTP. Activated by the G protein coupled
CC receptors (GPCRs) STE2 and STE3, which serve as guanine nucleotide-
CC exchange factors (GEFs), and inactivated by SST2, probably acting as a
CC GTPase-activating protein (GAP). {ECO:0000269|PubMed:16467474}.
CC -!- SUBUNIT: G proteins are composed of 3 units; alpha, beta and gamma. The
CC alpha chain contains the guanine nucleotide binding site. In its GDP-
CC bound form, binds to the G protein beta-gamma dimer STE4-STE18.
CC Directly interacts with the beta subunit STE4. Probably forms
CC preactivation complexes with unligated receptors STE2 and STE3.
CC Interacts with FUS3. Pheromone-induced activation of GPA1 increases its
CC association with FUS3. Interacts with SCP160. SCP160 binds specifically
CC to the GTP-bound form of GPA1. Interacts with the phoshpatidylinositol
CC 3-kinase (PI3K) subunits VPS15 and VPS34 at the endosome. The GTP-bound
CC form of GPA1 binds directly and selectively to the catalytic subunit
CC VPS34, while the GDP-bound form binds to VPS15, which appears to
CC function as an alternative G protein beta subunit for GPA1. Interacts
CC with regulators of G protein signaling (RGS) proteins MDM1, RAX1, RGS2
CC and SST2, but SST2 alone binds preferentially to the transition state
CC conformation of GPA1, indicating that it acts as a GAP for this G
CC protein. {ECO:0000269|PubMed:12029138, ECO:0000269|PubMed:14536090,
CC ECO:0000269|PubMed:16467474, ECO:0000269|PubMed:16839886,
CC ECO:0000269|PubMed:8417317, ECO:0000269|PubMed:8756677,
CC ECO:0000269|PubMed:9537998}.
CC -!- INTERACTION:
CC P08539; P11972: SST2; NbExp=3; IntAct=EBI-7376, EBI-18232;
CC P08539; P18851: STE4; NbExp=8; IntAct=EBI-7376, EBI-7390;
CC P08539; P22219: VPS15; NbExp=2; IntAct=EBI-7376, EBI-20347;
CC P08539; P22543: VPS34; NbExp=3; IntAct=EBI-7376, EBI-20405;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic side.
CC Endosome membrane; Lipid-anchor; Cytoplasmic side. Note=Localizes
CC predominantly to the plasma membrane in its inactive, GDP-bound form,
CC and is directed to endosomes once in its active, GTP-bound form.
CC Concentrates at the tip of the mating projections.
CC -!- DOMAIN: Contains an 'insertion' sequence of 109 residues which is not
CC present in other G-protein alpha chains.
CC -!- PTM: N-myristoylation by NMT1 is pheromone-stimulated and required for
CC palmitoylation of Cys-3. This lipid modification anchors the protein to
CC membranes. Depalmitoylated by YLR118C/APT1.
CC {ECO:0000269|PubMed:10712512, ECO:0000269|PubMed:1936988,
CC ECO:0000269|PubMed:8415763, ECO:0000269|PubMed:8702760,
CC ECO:0000269|PubMed:8942643}.
CC -!- PTM: Monoubiquitination targets the protein for degradation to the
CC vacuole, and polyubiquitination tags the protein for degradation by the
CC proteasome. This may be an additional signaling regulation mechanism.
CC {ECO:0000269|PubMed:11955054}.
CC -!- MISCELLANEOUS: Present with 9920 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(q) subfamily.
CC {ECO:0000305}.
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DR EMBL; M15867; AAA34650.1; -; Genomic_DNA.
DR EMBL; M17414; AAA18403.1; -; Unassigned_DNA.
DR EMBL; U10555; AAB68432.1; -; Genomic_DNA.
DR EMBL; AY692963; AAT92982.1; -; Genomic_DNA.
DR EMBL; BK006934; DAA06692.1; -; Genomic_DNA.
DR PIR; A25906; A25906.
DR RefSeq; NP_011868.1; NM_001179135.1.
DR PDB; 7AD3; EM; 3.50 A; E/H=300-472.
DR PDBsum; 7AD3; -.
DR AlphaFoldDB; P08539; -.
DR SMR; P08539; -.
DR BioGRID; 36430; 58.
DR ComplexPortal; CPX-1646; G protein heterotrimer.
DR DIP; DIP-15N; -.
DR IntAct; P08539; 17.
DR MINT; P08539; -.
DR STRING; 4932.YHR005C; -.
DR iPTMnet; P08539; -.
DR SwissPalm; P08539; -.
DR MaxQB; P08539; -.
DR PaxDb; P08539; -.
DR PRIDE; P08539; -.
DR DNASU; 856394; -.
DR EnsemblFungi; YHR005C_mRNA; YHR005C; YHR005C.
DR GeneID; 856394; -.
DR KEGG; sce:YHR005C; -.
DR SGD; S000001047; GPA1.
DR VEuPathDB; FungiDB:YHR005C; -.
DR eggNOG; KOG0082; Eukaryota.
DR GeneTree; ENSGT00940000168787; -.
DR HOGENOM; CLU_014184_2_0_1; -.
DR InParanoid; P08539; -.
DR OMA; QVIWADA; -.
DR BioCyc; YEAST:G3O-31070-MON; -.
DR PRO; PR:P08539; -.
DR Proteomes; UP000002311; Chromosome VIII.
DR RNAct; P08539; protein.
DR GO; GO:0005829; C:cytosol; HDA:SGD.
DR GO; GO:0005768; C:endosome; IDA:SGD.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IDA:SGD.
DR GO; GO:0005886; C:plasma membrane; IDA:SGD.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0031681; F:G-protein beta-subunit binding; IPI:SGD.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000754; P:adaptation of signaling pathway by response to pheromone involved in conjugation with cellular fusion; IMP:SGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:InterPro.
DR GO; GO:0048017; P:inositol lipid-mediated signaling; IMP:SGD.
DR GO; GO:0000742; P:karyogamy involved in conjugation with cellular fusion; IMP:SGD.
DR GO; GO:0000743; P:nuclear migration involved in conjugation with cellular fusion; IMP:SGD.
DR GO; GO:0000750; P:pheromone-dependent signal transduction involved in conjugation with cellular fusion; IDA:ComplexPortal.
DR GO; GO:0071701; P:regulation of MAPK export from nucleus; IMP:SGD.
DR CDD; cd00066; G-alpha; 1.
DR Gene3D; 1.10.400.10; -; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR002975; Fungi_Gprotein_alpha.
DR InterPro; IPR001019; Gprotein_alpha_su.
DR InterPro; IPR011025; GproteinA_insert.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR10218; PTHR10218; 1.
DR Pfam; PF00503; G-alpha; 1.
DR PRINTS; PR00318; GPROTEINA.
DR PRINTS; PR01241; GPROTEINAFNG.
DR SMART; SM00275; G_alpha; 1.
DR SUPFAM; SSF47895; SSF47895; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51882; G_ALPHA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Endosome; GTP-binding; Isopeptide bond;
KW Lipoprotein; Magnesium; Membrane; Metal-binding; Myristate;
KW Nucleotide-binding; Palmitate; Pheromone response; Reference proteome;
KW Transducer; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..472
FT /note="Guanine nucleotide-binding protein alpha-1 subunit"
FT /id="PRO_0000203616"
FT DOMAIN 40..472
FT /note="G-alpha"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 43..56
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 127..235
FT /note="Insert; not present in other G-proteins"
FT REGION 162..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 292..300
FT /note="G2 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 315..324
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 384..391
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 442..447
FT /note="G5 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT COMPBIAS 175..191
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 48..55
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 55
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 294..300
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 300
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 319..323
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 388..391
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 444
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:1936988,
FT ECO:0000269|PubMed:8415763, ECO:0000269|PubMed:8702760"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:10712512,
FT ECO:0000269|PubMed:8942643"
FT CROSSLNK 165
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:11955054"
FT MUTAGEN 2
FT /note="G->A: Abolishes both palmitoylation and N-
FT myristoylation."
FT /evidence="ECO:0000269|PubMed:10712512,
FT ECO:0000269|PubMed:8702760, ECO:0000269|PubMed:8942643"
FT MUTAGEN 3
FT /note="C->A: Abolishes palmitoylation but not N-
FT myristoylation."
FT /evidence="ECO:0000269|PubMed:10712512,
FT ECO:0000269|PubMed:8942643"
FT MUTAGEN 15
FT /note="D->V: Slightly reduces ligand-dependent pheromone
FT signaling."
FT /evidence="ECO:0000269|PubMed:14767760"
FT MUTAGEN 17
FT /note="F->L: Leads to a hypersensitive signaling phenotype
FT resulting in greatly enhanced signal at low alpha-factor
FT concentrations."
FT /evidence="ECO:0000269|PubMed:14767760"
FT MUTAGEN 18
FT /note="L->P,Q: Reduces ligand-dependent pheromone
FT signaling."
FT /evidence="ECO:0000269|PubMed:14767760"
FT MUTAGEN 21..22
FT /note="KR->EE: Impairs interaction with FUS3."
FT /evidence="ECO:0000269|PubMed:12029138"
FT MUTAGEN 50
FT /note="G->D: Confers insensitivity to pheromone."
FT /evidence="ECO:0000269|PubMed:10705368,
FT ECO:0000269|PubMed:1900495, ECO:0000269|PubMed:2117698,
FT ECO:0000269|PubMed:2548076"
FT MUTAGEN 50
FT /note="G->V: Has increased GTP occupancy and moderately
FT reduces hydrolysis of GTP, resulting in a constitutively
FT active form that down-regulates the pheromone response and
FT causes hyperadaptation to pheromone."
FT /evidence="ECO:0000269|PubMed:10705368,
FT ECO:0000269|PubMed:1900495, ECO:0000269|PubMed:2117698,
FT ECO:0000269|PubMed:2548076"
FT MUTAGEN 54
FT /note="K->E,I: Prevents GDP to GTP exchange; suppressor of
FT L-323."
FT /evidence="ECO:0000269|PubMed:14767760,
FT ECO:0000269|PubMed:9786851"
FT MUTAGEN 165
FT /note="K->R: Substantial decrease in ubiquitination."
FT /evidence="ECO:0000269|PubMed:11955054"
FT MUTAGEN 297
FT /note="R->H: Slows hydrolysis of GTP."
FT MUTAGEN 302
FT /note="G->S: In GPA1(SST); weakens interaction to SST2 and
FT blocks its negative regulatory effect."
FT /evidence="ECO:0000269|PubMed:9488712"
FT MUTAGEN 321
FT /note="G->T: Causes a specific mating defect in alpha
FT cells."
FT /evidence="ECO:0000269|PubMed:9604890"
FT MUTAGEN 322
FT /note="G->A,E,R: Confers insensitivity to pheromone."
FT /evidence="ECO:0000269|PubMed:1900495,
FT ECO:0000269|PubMed:2117698, ECO:0000269|PubMed:8887662"
FT MUTAGEN 323
FT /note="Q->L: Prevents hydrolysis of GTP; eliminates the
FT interaction with STE4 and constitutively activates the
FT pheromone response pathway."
FT /evidence="ECO:0000269|PubMed:9604890"
FT MUTAGEN 327
FT /note="R->S: Suppressor of L-323; does not prevent GTP
FT binding to GPA1."
FT /evidence="ECO:0000269|PubMed:9786851"
FT MUTAGEN 345
FT /note="A->T: Suppressor of a STE2-L236H mutant."
FT /evidence="ECO:0000269|PubMed:10866688"
FT MUTAGEN 353
FT /note="Missing: Suppressor of L-323."
FT /evidence="ECO:0000269|PubMed:9786851"
FT MUTAGEN 355
FT /note="E->K: Confers insensitivity to pheromone."
FT /evidence="ECO:0000269|PubMed:2117698"
FT MUTAGEN 364
FT /note="E->K: Enhances the rate of GDP for GTP exchange and
FT slows hydrolysis of GTP, resulting in a constitutively
FT active form that down-regulates the pheromone response
FT independently of the pheromone receptor."
FT /evidence="ECO:0000269|PubMed:11394869,
FT ECO:0000269|PubMed:2117698, ECO:0000269|PubMed:8887662"
FT MUTAGEN 388
FT /note="N->D: Forms a nondissociable complex with the
FT pheromone receptor in response to receptor activation,
FT resulting in reduced pheromone responsiveness."
FT /evidence="ECO:0000269|PubMed:11394869,
FT ECO:0000269|PubMed:15197187, ECO:0000269|PubMed:1900495,
FT ECO:0000269|PubMed:8887662"
FT MUTAGEN 388
FT /note="N->K: Causes constitutive activation of the
FT pheromone response pathway."
FT /evidence="ECO:0000269|PubMed:11394869,
FT ECO:0000269|PubMed:15197187, ECO:0000269|PubMed:1900495,
FT ECO:0000269|PubMed:8887662"
FT MUTAGEN 391
FT /note="D->A: Causes constitutive activation of the
FT pheromone response pathway."
FT /evidence="ECO:0000269|PubMed:1900495"
FT MUTAGEN 467
FT /note="K->P: Impairs pheromone signaling in a and alpha
FT cells."
FT /evidence="ECO:0000269|PubMed:1848203"
FT MUTAGEN 468
FT /note="K->P: Impairs pheromone signaling specifically in a
FT cells."
FT /evidence="ECO:0000269|PubMed:1848203"
FT MUTAGEN 470
FT /note="G->D: Confers insensitivity to pheromone."
FT /evidence="ECO:0000269|PubMed:2117698"
FT CONFLICT 82
FT /note="W -> R (in Ref. 2; AAA18403)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="A -> V (in Ref. 2; AAA18403)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="R -> K (in Ref. 2; AAA18403)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="K -> R (in Ref. 2; AAA18403)"
FT /evidence="ECO:0000305"
FT CONFLICT 469
FT /note="I -> S (in Ref. 2; AAA18403)"
FT /evidence="ECO:0000305"
FT STRAND 303..309
FT /evidence="ECO:0007829|PDB:7AD3"
FT STRAND 311..319
FT /evidence="ECO:0007829|PDB:7AD3"
FT TURN 325..329
FT /evidence="ECO:0007829|PDB:7AD3"
FT HELIX 330..335
FT /evidence="ECO:0007829|PDB:7AD3"
FT STRAND 338..344
FT /evidence="ECO:0007829|PDB:7AD3"
FT HELIX 360..373
FT /evidence="ECO:0007829|PDB:7AD3"
FT STRAND 379..381
FT /evidence="ECO:0007829|PDB:7AD3"
FT STRAND 383..388
FT /evidence="ECO:0007829|PDB:7AD3"
FT HELIX 390..396
FT /evidence="ECO:0007829|PDB:7AD3"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:7AD3"
FT HELIX 417..428
FT /evidence="ECO:0007829|PDB:7AD3"
FT STRAND 437..441
FT /evidence="ECO:0007829|PDB:7AD3"
FT HELIX 450..465
FT /evidence="ECO:0007829|PDB:7AD3"
FT TURN 466..468
FT /evidence="ECO:0007829|PDB:7AD3"
SQ SEQUENCE 472 AA; 54076 MW; 2E87C546E133D6E5 CRC64;
MGCTVSTQTI GDESDPFLQN KRANDVIEQS LQLEKQRDKN EIKLLLLGAG ESGKSTVLKQ
LKLLHQGGFS HQERLQYAQV IWADAIQSMK ILIIQARKLG IQLDCDDPIN NKDLFACKRI
LLKAKALDYI NASVAGGSDF LNDYVLKYSE RYETRRRVQS TGRAKAAFDE DGNISNVKSD
TDRDAETVTQ NEDADRNNSS RINLQDICKD LNQEGDDQMF VRKTSREIQG QNRRNLIHED
IAKAIKQLWN NDKGIKQCFA RSNEFQLEGS AAYYFDNIEK FASPNYVCTD EDILKGRIKT
TGITETEFNI GSSKFKVLDA GGQRSERKKW IHCFEGITAV LFVLAMSEYD QMLFEDERVN
RMHESIMLFD TLLNSKWFKD TPFILFLNKI DLFEEKVKSM PIRKYFPDYQ GRVGDAEAGL
KYFEKIFLSL NKTNKPIYVK RTCATDTQTM KFVLSAVTDL IIQQNLKKIG II
