GPA2_YEAST
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 03-AUG-2022, entry version 212.
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; 88.
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; P10823; -.
DR PRIDE; P10823; -.
DR EnsemblFungi; YER020W_mRNA; YER020W; YER020W.
DR GeneID; 856741; -.
DR KEGG; sce:YER020W; -.
DR SGD; S000000822; GPA2.
DR VEuPathDB; FungiDB:YER020W; -.
DR eggNOG; KOG0082; Eukaryota.
DR HOGENOM; CLU_014184_0_2_1; -.
DR InParanoid; P10823; -.
DR OMA; AVTYLWN; -.
DR BioCyc; YEAST:G3O-30204-MON; -.
DR Reactome; R-SCE-112043; PLC beta mediated events.
DR Reactome; R-SCE-202040; G-protein activation.
DR Reactome; R-SCE-2485179; Activation of the phototransduction cascade.
DR Reactome; R-SCE-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR Reactome; R-SCE-399997; Acetylcholine regulates insulin secretion.
DR Reactome; R-SCE-4086398; Ca2+ pathway.
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 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:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
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; -; 1.
DR Gene3D; 3.40.50.300; -; 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; 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 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 N-
FT myristoylation."
FT /evidence="ECO:0000269|PubMed:16030250"
FT MUTAGEN 4
FT /note="C->A: Abolishes palmitoylation but not N-
FT myristoylation."
FT /evidence="ECO:0000269|PubMed:16030250"
FT MUTAGEN 6
FT /note="S->A: Abolishes both palmitoylation and N-
FT 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
