ID   GPA2_YEAST              Reviewed;         449 AA.
AC   P10823; D3DLR9;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 2.
DT   27-MAR-2024, entry version 219.
DE   RecName: Full=Guanine nucleotide-binding protein alpha-2 subunit;
DE   AltName: Full=GP2-alpha;
GN   Name=GPA2; Synonyms=SSP101; OrderedLocusNames=YER020W;
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=2830616; DOI=10.1073/pnas.85.5.1374;
RA   Nakafuku M., Obara T., Kaibuchi K., Miyajima I., Miyajima A., Itoh H.,
RA   Nakamura S., Arai K., Matsumoto K., Kaziro Y.;
RT   "Isolation of a second yeast Saccharomyces cerevisiae gene (GPA2) coding
RT   for guanine nucleotide-binding regulatory protein: studies on its structure
RT   and possible functions.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:1374-1378(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169868;
RA   Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA   Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA   Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA   Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA   Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA   Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA   Botstein D., Davis R.W.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL   Nature 387:78-81(1997).
RN   [3]
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   [4]
RP   FUNCTION, INTERACTION WITH RGS2, AND MUTAGENESIS OF GLY-132.
RX   PubMed=10523302; DOI=10.1093/emboj/18.20.5577;
RA   Versele M., de Winde J.H., Thevelein J.M.;
RT   "A novel regulator of G protein signalling in yeast, Rgs2, downregulates
RT   glucose-activation of the cAMP pathway through direct inhibition of Gpa2.";
RL   EMBO J. 18:5577-5591(1999).
RN   [5]
RP   INTERACTION WITH GPG1; GPB1 AND GPB2, AND MUTAGENESIS OF GLY-132; GLY-299
RP   AND GLN-300.
RX   PubMed=12150916; DOI=10.1016/s1097-2765(02)00569-5;
RA   Harashima T., Heitman J.;
RT   "The Galpha protein Gpa2 controls yeast differentiation by interacting with
RT   kelch repeat proteins that mimic Gbeta subunits.";
RL   Mol. Cell 10:163-173(2002).
RN   [6]
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   [7]
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   [8]
RP   FUNCTION, MYRISTOYLATION AT GLY-2, PALMITOYLATION AT CYS-4, MUTAGENESIS OF
RP   GLY-2; CYS-4; SER-6 AND GLY-299, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP   GPB2 AND GPR1.
RX   PubMed=16030250; DOI=10.1091/mbc.e05-05-0403;
RA   Harashima T., Heitman J.;
RT   "Galpha subunit Gpa2 recruits kelch repeat subunits that inhibit receptor-G
RT   protein coupling during cAMP-induced dimorphic transitions in Saccharomyces
RT   cerevisiae.";
RL   Mol. Biol. Cell 16:4557-4571(2005).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [10]
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) involved in glucose-induced cAMP signaling.
CC       Binds to its cognate transmembrane receptor GPR1, which senses
CC       extracellular carbon sources, and activates cAMP-PKA signaling and
CC       governs diploid pseudohyphal differentiation and haploid invasive
CC       growth. The G protein beta-mimic proteins GPB1 and GPB2 inhibit GPA2-
CC       GPR1 coupling, probably to reduce signaling in the absence of glucose.
CC       {ECO:0000269|PubMed:10523302, ECO:0000269|PubMed:16030250}.
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       receptor (GPCR) GPR1, which serves as a guanine nucleotide-exchange
CC       factor (GEF), and inactivated by RGS2, acting as a GTPase-activating
CC       protein (GAP) for GPA2.
CC   -!- SUBUNIT: G proteins are composed of 3 units; alpha, beta and gamma. The
CC       alpha chain contains the guanine nucleotide binding site. GPA2
CC       interacts with the kelch repeat beta-mimic proteins GPB1 and GPB2 and
CC       with the gamma subunit GPG1. Interacts with the G protein coupled
CC       receptor GPR1. Interacts also with regulators of G protein signaling
CC       (RGS) protein RGS2. {ECO:0000269|PubMed:10523302,
CC       ECO:0000269|PubMed:12150916, ECO:0000269|PubMed:16030250}.
CC   -!- INTERACTION:
CC       P10823; P08678: CYR1; NbExp=3; IntAct=EBI-7382, EBI-5364;
CC       P10823; P39717: GPB2; NbExp=4; IntAct=EBI-7382, EBI-20711;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14562095,
CC       ECO:0000269|PubMed:16030250}; Lipid-anchor
CC       {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:16030250}; Cytoplasmic
CC       side {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:16030250}.
CC   -!- PTM: Myristoylation at Gly-2 and palmitoylation at Cys-4 are required
CC       for membrane localization and function of the protein.
CC       {ECO:0000269|PubMed:16030250}.
CC   -!- MISCELLANEOUS: Present with 4570 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; J03609; AAA34651.1; -; Genomic_DNA.
DR   EMBL; U18778; AAB64553.1; -; Genomic_DNA.
DR   EMBL; BK006939; DAA07673.1; -; Genomic_DNA.
DR   PIR; S50478; S50478.
DR   RefSeq; NP_010937.3; NM_001178911.3.
DR   AlphaFoldDB; P10823; -.
DR   SMR; P10823; -.
DR   BioGRID; 36754; 92.
DR   DIP; DIP-4346N; -.
DR   IntAct; P10823; 51.
DR   MINT; P10823; -.
DR   STRING; 4932.YER020W; -.
DR   TCDB; 8.A.92.1.15; the g-protein AlphaBetaGama complex (gpc) family.
DR   iPTMnet; P10823; -.
DR   SwissPalm; P10823; -.
DR   MaxQB; P10823; -.
DR   PaxDb; 4932-YER020W; -.
DR   PeptideAtlas; P10823; -.
DR   EnsemblFungi; YER020W_mRNA; YER020W; YER020W.
DR   GeneID; 856741; -.
DR   KEGG; sce:YER020W; -.
DR   AGR; SGD:S000000822; -.
DR   SGD; S000000822; GPA2.
DR   VEuPathDB; FungiDB:YER020W; -.
DR   eggNOG; KOG0082; Eukaryota.
DR   HOGENOM; CLU_014184_0_2_1; -.
DR   InParanoid; P10823; -.
DR   OMA; EHQSEFY; -.
DR   OrthoDB; 2897309at2759; -.
DR   BioCyc; YEAST:G3O-30204-MONOMER; -.
DR   Reactome; R-SCE-112043; PLC beta mediated events.
DR   Reactome; R-SCE-202040; G-protein activation.
DR   Reactome; R-SCE-399997; Acetylcholine regulates insulin secretion.
DR   Reactome; R-SCE-416476; G alpha (q) signalling events.
DR   Reactome; R-SCE-416482; G alpha (12/13) signalling events.
DR   Reactome; R-SCE-418592; ADP signalling through P2Y purinoceptor 1.
DR   Reactome; R-SCE-434316; Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion.
DR   Reactome; R-SCE-9013148; CDC42 GTPase cycle.
DR   Reactome; R-SCE-9013149; RAC1 GTPase cycle.
DR   BioGRID-ORCS; 856741; 3 hits in 10 CRISPR screens.
DR   PRO; PR:P10823; -.
DR   Proteomes; UP000002311; Chromosome V.
DR   RNAct; P10823; Protein.
DR   GO; GO:0005829; C:cytosol; HDA:SGD.
DR   GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
DR   GO; GO:0005739; C:mitochondrion; HDA: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: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:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:SGD.
DR   GO; GO:0030437; P:ascospore formation; IMP:SGD.
DR   GO; GO:0010255; P:glucose mediated signaling pathway; IMP:SGD.
DR   GO; GO:0009757; P:hexose mediated signaling; IMP:SGD.
DR   GO; GO:0001403; P:invasive growth in response to glucose limitation; IMP:SGD.
DR   GO; GO:0010737; P:protein kinase A signaling; IDA:SGD.
DR   GO; GO:0007124; P:pseudohyphal growth; IMP:SGD.
DR   GO; GO:0008361; P:regulation of cell size; HMP:SGD.
DR   GO; GO:0007165; P:signal transduction; IMP:SGD.
DR   CDD; cd00066; G-alpha; 1.
DR   Gene3D; 1.10.400.10; GI Alpha 1, domain 2-like; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
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; GTP-BINDING PROTEIN ALPHA SUBUNIT; 1.
DR   PANTHER; PTHR10218:SF363; GUANINE NUCLEOTIDE-BINDING PROTEIN ALPHA-2 SUBUNIT; 1.
DR   Pfam; PF00503; G-alpha; 1.
DR   PRINTS; PR00318; GPROTEINA.
DR   PRINTS; PR01241; GPROTEINAFNG.
DR   SMART; SM00275; G_alpha; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF47895; Transducin (alpha subunit), insertion domain; 1.
DR   PROSITE; PS51882; G_ALPHA; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; GTP-binding; Lipoprotein; Magnesium; Membrane;
KW   Metal-binding; Myristate; Nucleotide-binding; Palmitate;
KW   Reference proteome; Transducer.
FT   INIT_MET        1
FT                   /note="Removed"
FT   CHAIN           2..449
FT                   /note="Guanine nucleotide-binding protein alpha-2 subunit"
FT                   /id="PRO_0000203617"
FT   DOMAIN          122..448
FT                   /note="G-alpha"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT   REGION          1..91
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          125..138
FT                   /note="G1 motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT   REGION          268..276
FT                   /note="G2 motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT   REGION          292..301
FT                   /note="G3 motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT   REGION          361..368
FT                   /note="G4 motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT   REGION          418..423
FT                   /note="G5 motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT   COMPBIAS        1..24
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        38..61
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        71..91
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         130..137
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   BINDING         137
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         270..276
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   BINDING         276
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         296..300
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   BINDING         365..368
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250"
FT   BINDING         420
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:16030250"
FT   LIPID           4
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000269|PubMed:16030250"
FT   MUTAGEN         2
FT                   /note="G->A: Abolishes both palmitoylation and
FT                   N-myristoylation."
FT                   /evidence="ECO:0000269|PubMed:16030250"
FT   MUTAGEN         4
FT                   /note="C->A: Abolishes palmitoylation but not
FT                   N-myristoylation."
FT                   /evidence="ECO:0000269|PubMed:16030250"
FT   MUTAGEN         6
FT                   /note="S->A: Abolishes both palmitoylation and
FT                   N-myristoylation."
FT                   /evidence="ECO:0000269|PubMed:16030250"
FT   MUTAGEN         132
FT                   /note="G->V: Locks GPA2 in its activated GTP-bound form and
FT                   abrogates the negative control by RGS2."
FT                   /evidence="ECO:0000269|PubMed:10523302,
FT                   ECO:0000269|PubMed:12150916"
FT   MUTAGEN         299
FT                   /note="G->A: Dominant negative allele unable to undergo the
FT                   GTP-induced conformational change."
FT                   /evidence="ECO:0000269|PubMed:12150916,
FT                   ECO:0000269|PubMed:16030250"
FT   MUTAGEN         300
FT                   /note="Q->L: Dominant active allele that abolishes
FT                   intrinsic GTPase activity."
FT                   /evidence="ECO:0000269|PubMed:12150916"
FT   CONFLICT        375
FT                   /note="S -> R (in Ref. 1; AAA34651)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   449 AA;  50448 MW;  881B91792AE91748 CRC64;
     MGLCASSEKN GSTPDTQTAS AGSDNVGKAK VPPKQEPQKT VRTVNTANQQ EKQQQRQQQP
     SPHNVKDRKE QNGSINNAIS PTATANTSGS QQINIDSALR DRSSNVAAQP SLSDASSGSN
     DKELKVLLLG AGESGKSTVL QQLKILHQNG FSEQEIKEYI PLIYQNLLEI GRNLIQARTR
     FNVNLEPECE LTQQDLSRTM SYEMPNNYTG QFPEDIAGVI STLWALPSTQ DLVNGPNASK
     FYLMDSTPYF MENFTRITSP NYRPTQQDIL RSRQMTSGIF DTVIDMGSDI KMHIYDVGGQ
     RSERKKWIHC FDNVTLVIFC VSLSEYDQTL MEDKNQNRFQ ESLVLFDNIV NSRWFARTSV
     VLFLNKIDLF AEKLSKVPME NYFPDYTGGS DINKAAKYIL WRFVQLNRAN LSIYPHVTQA
     TDTSNIRLVF AAIKETILEN TLKDSGVLQ
//