ID   IRA2_YEAST              Reviewed;        3079 AA.
AC   P19158; D6W1Y7; O13592; Q08239;
DT   01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT   05-SEP-2006, sequence version 2.
DT   27-MAR-2024, entry version 191.
DE   RecName: Full=Inhibitory regulator protein IRA2;
GN   Name=IRA2; Synonyms=CCS1, GLC4; OrderedLocusNames=YOL081W;
GN   ORFNames=O0985;
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=2164637; DOI=10.1128/mcb.10.8.4303-4313.1990;
RA   Tanaka K., Nakafuku M., Tamanoi F., Kaziro Y., Matsumoto K., Toh-e A.;
RT   "IRA2, a second gene of Saccharomyces cerevisiae that encodes a protein
RT   with a domain homologous to mammalian ras GTPase-activating protein.";
RL   Mol. Cell. Biol. 10:4303-4313(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169874;
RA   Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA   Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA   Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA   Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA   Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA   Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA   Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA   Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA   Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA   Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA   Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA   Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA   Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA   Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA   Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA   Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL   Nature 387:98-102(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   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-2423.
RC   STRAIN=ATCC 96604 / S288c / FY1679;
RX   PubMed=7900427; DOI=10.1002/yea.320101015;
RA   Zumstein E., Griffin H., Schweizer M.;
RT   "Sequence of a 10.27 kb segment on the left arm of chromosome XV from
RT   Saccharomyces cerevisiae includes part of the IRA2 gene and a putative new
RT   gene.";
RL   Yeast 10:1383-1387(1994).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-2423.
RC   STRAIN=ATCC 96604 / S288c / FY1679;
RX   PubMed=8533473; DOI=10.1002/yea.320111009;
RA   Zumstein E., Pearson B.M., Kalogeropoulos A., Schweizer M.;
RT   "A 29.425 kb segment on the left arm of yeast chromosome XV contains more
RT   than twice as many unknown as known open reading frames.";
RL   Yeast 11:975-986(1995).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1982-3079.
RX   PubMed=9178509;
RX   DOI=10.1002/(sici)1097-0061(199705)13:6<583::aid-yea111>3.0.co;2-y;
RA   Tzermia M., Katsoulou C., Alexandraki D.;
RT   "Sequence analysis of a 33.2 kb segment from the left arm of yeast
RT   chromosome XV reveals eight known genes and ten new open reading frames
RT   including homologues of ABC transporters, inositol phosphatases and human
RT   expressed sequence tags.";
RL   Yeast 13:583-589(1997).
RN   [7]
RP   IDENTIFICATION OF CCS1 AS IRA2.
RX   PubMed=1326414; DOI=10.1007/bf00351690;
RA   Bussereau F., Dupont C.H., Boy-Marcotte E., Mallet L., Jacquet M.;
RT   "The CCS1 gene from Saccharomyces cerevisiae which is involved in
RT   mitochondrial functions is identified as IRA2 an attenuator of RAS1 and
RT   RAS2 gene products.";
RL   Curr. Genet. 21:325-329(1992).
RN   [8]
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   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA   Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA   Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT   "Analysis of phosphorylation sites on proteins from Saccharomyces
RT   cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN   [10]
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   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-635, AND IDENTIFICATION BY
RP   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: Inhibitory regulator of the Ras-cyclic AMP pathway.
CC       Stimulates the GTPase activity of Ras proteins.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}.
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DR   EMBL; M33779; AAA34710.1; -; Genomic_DNA.
DR   EMBL; Z74823; CAA99093.1; -; Genomic_DNA.
DR   EMBL; X75449; CAA53202.1; -; Genomic_DNA.
DR   EMBL; X83121; CAA58201.1; -; Genomic_DNA.
DR   EMBL; Z74822; CAA99092.1; -; Genomic_DNA.
DR   EMBL; BK006948; DAA10703.1; -; Genomic_DNA.
DR   PIR; S66775; RGBYI2.
DR   RefSeq; NP_014560.1; NM_001183335.1.
DR   SMR; P19158; -.
DR   BioGRID; 34321; 1000.
DR   DIP; DIP-6376N; -.
DR   IntAct; P19158; 4.
DR   MINT; P19158; -.
DR   STRING; 4932.YOL081W; -.
DR   iPTMnet; P19158; -.
DR   MaxQB; P19158; -.
DR   PaxDb; 4932-YOL081W; -.
DR   PeptideAtlas; P19158; -.
DR   EnsemblFungi; YOL081W_mRNA; YOL081W; YOL081W.
DR   GeneID; 854073; -.
DR   KEGG; sce:YOL081W; -.
DR   AGR; SGD:S000005441; -.
DR   SGD; S000005441; IRA2.
DR   VEuPathDB; FungiDB:YOL081W; -.
DR   eggNOG; KOG1826; Eukaryota.
DR   GeneTree; ENSGT00940000176574; -.
DR   HOGENOM; CLU_000439_0_0_1; -.
DR   InParanoid; P19158; -.
DR   OMA; WSELMIL; -.
DR   OrthoDB; 1356198at2759; -.
DR   BioCyc; YEAST:G3O-33484-MONOMER; -.
DR   BioGRID-ORCS; 854073; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P19158; -.
DR   Proteomes; UP000002311; Chromosome XV.
DR   RNAct; P19158; Protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005829; C:cytosol; HDA:SGD.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:SGD.
DR   GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR   GO; GO:0005096; F:GTPase activator activity; IDA:SGD.
DR   GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IMP:SGD.
DR   GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IMP:SGD.
DR   CDD; cd05392; RasGAP_Neurofibromin_like; 1.
DR   Gene3D; 3.40.525.10; CRAL-TRIO lipid binding domain; 1.
DR   InterPro; IPR036865; CRAL-TRIO_dom_sf.
DR   InterPro; IPR039360; Ras_GTPase.
DR   InterPro; IPR023152; RasGAP_CS.
DR   InterPro; IPR001936; RasGAP_dom.
DR   InterPro; IPR008936; Rho_GTPase_activation_prot.
DR   PANTHER; PTHR10194:SF150; INHIBITORY REGULATOR PROTEIN IRA1-RELATED; 1.
DR   PANTHER; PTHR10194; RAS GTPASE-ACTIVATING PROTEINS; 1.
DR   Pfam; PF00616; RasGAP; 2.
DR   SMART; SM00323; RasGAP; 1.
DR   SUPFAM; SSF48350; GTPase activation domain, GAP; 1.
DR   PROSITE; PS00509; RAS_GTPASE_ACTIV_1; 1.
DR   PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; GTPase activation; Phosphoprotein; Reference proteome.
FT   CHAIN           1..3079
FT                   /note="Inhibitory regulator protein IRA2"
FT                   /id="PRO_0000056658"
FT   DOMAIN          1701..1890
FT                   /note="Ras-GAP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00167"
FT   REGION          392..554
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          867..898
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          912..935
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          952..980
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        392..550
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        869..895
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        957..980
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         635
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   CONFLICT        2309
FT                   /note="D -> V (in Ref. 1; AAA34710)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        2317
FT                   /note="K -> I (in Ref. 1; AAA34710)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   3079 AA;  351669 MW;  C14B5396D6FB9B5C CRC64;
     MSQPTKNKKK EHGTDSKSSR MTRTLVNHIL FERILPILPV ESNLSTYSEV EEYSSFISCR
     SVLINVTVSR DANAMVEGTL ELIESLLQGH EIISDKGSSD VIESILIILR LLSDALEYNW
     QNQESLHYND ISTHVEHDQE QKYRPKLNSI LPDYSSTHSN GNKHFFHQSK PQALIPELAS
     KLLESCAKLK FNTRTLQILQ NMISHVHGNI LTTLSSSILP RHKSYLTRHN HPSHCKMIDS
     TLGHILRFVA ASNPSEYFEF IRKSVQVPVT QTHTHSHSHS HSLPSSVYNS IVPHFDLFSF
     IYLSKHNFKK YLELIKNLSV TLRKTIYHCL LLHYSAKAIM FWIMARPAEY YELFNLLKDN
     NNEHSKSLNT LNHTLFEEIH STFNVNSMIT TNQNAHQGSS SPSSSSPSSP PSSSSSDNNN
     QNIIAKSLSR QLSHHQSYIQ QQSERKLHSS WTTNSQSSTS LSSSTSNSTT TDFSTHTQPG
     EYDPSLPDTP TMSNITISAS SLLSQTPTPT TQLQQRLNSA AAAAAAAASP SNSTPTGYTA
     EQQSRASYDA HKTGHTGKDY DEHFLSVTRL DNVLELYTHF DDTEVLPHTS VLKFLTTLTM
     FDIDLFNELN ATSFKYIPDC TMHRPKERTS SFNNTAHETG SEKTSGIKHI TQGLKKLTSL
     PSSTKKTVKF VKMLLRNLNG NQAVSDVALL DTMRALLSFF TMTSAVFLVD RNLPSVLFAK
     RLIPIMGTNL SVGQDWNSKI NNSLMVCLKK NSTTFVQLQL IFFSSAIQFD HELLLARLSI
     DTMANNLNMQ KLCLYTEGFR IFFDIPSKKE LRKAIAVKIS KFFKTLFSII ADILLQEFPY
     FDEQITDIVA SILDGTIINE YGTKKHFKGS SPSLCSTTRS RSGSTSQSSM TPVSPLGLDT
     DICPMNTLSL VGSSTSRNSD NVNSLNSSPK NLSSDPYLSH LVAPRARHAL GGPSSIIRNK
     IPTTLTSPPG TEKSSPVQRP QTESISATPM AITNSTPLSS AAFGIRSPLQ KIRTRRYSDE
     SLGKFMKSTN NYIQEHLIPK DLNEATLQDA RRIMINIFSI FKRPNSYFII PHNINSNLQW
     VSQDFRNIMK PIFVAIVSPD VDLQNTAQSF MDTLLSNVIT YGESDENISI EGYHLLCSYT
     VTLFAMGLFD LKINNEKRQI LLDITVKFMK VRSHLAGIAE ASHHMEYISD SEKLTFPLIM
     GTVGRALFVS LYSSQQKIEK TLKIAYTEYL SAINFHERNI DDADKTWVHN IEFVEAMCHD
     NYTTSGSIAF QRRTRNNILR FATIPNAILL DSMRMIYKKW HTYTHSKSLE KQERNDFRNF
     AGILASLSGI LFINKKILQE MYPYLLDTVS ELKKNIDSFI SKQCQWLNYP DLLTRENSRD
     ILSVELHPLS FNLLFNNLRL KLKELACSDL SIPENESSYV LLEQIIKMLR TILGRDDDNY
     VMMLFSTEIV DLIDLLTDEI KKIPAYCPKY LKAIIQMTKM FSALQHSEVN LGVKNHFHVK
     NKWLRQITDW FQVSIAREYD FENLSKPLKE MDLVKRDMDI LYIDTAIEAS TAIAYLTRHT
     FLEIPPAASD PELSRSRSVI FGFYFNILMK GLEKSSDRDN YPVFLRHKMS VLNDNVILSL
     TNLSNTNVDA SLQFTLPMGY SGNRNIRNAF LEVFINIVTN YRTYTAKTDL GKLEAADKFL
     RYTIEHPQLS SFGAAVCPAS DIDAYAAGLI NAFETRNATH IVVAQLIKNE IEKSSRPTDI
     LRRNSCATRS LSMLARSKGN EYLIRTLQPL LKKIIQNRDF FEIEKLKPED SDAERQIELF
     VKYMNELLES ISNSVSYFPP PLFYICQNIY KVACEKFPDH AIIAAGSFVF LRFFCPALVS
     PDSENIIDIS HLSEKRTFIS LAKVIQNIAN GSENFSRWPA LCSQKDFLKE CSDRIFRFLA
     ELCRTDRTID IQVRTDPTPI AFDYQFLHSF VYLYGLEVRR NVLNEAKHDD GDIDGDDFYK
     TTFLLIDDVL GQLGQPKMEF SNEIPIYIRE HMDDYPELYE FMNRHAFRNI ETSTAYSPSV
     HESTSSEGIP IITLTMSNFS DRHVDIDTVA YKFLQIYARI WTTKHCLIID CTEFDEGGLD
     MRKFISLVMG LLPEVAPKNC IGCYYFNVNE TFMDNYGKCL DKDNVYVSSK IPHYFINSNS
     DEGLMKSVGI TGQGLKVLQD IRVSLHDITL YDEKRNRFTP VSLKIGDIYF QVLHETPRQY
     KIRDMGTLFD VKFNDVYEIS RIFEVHVSSI TGVAAEFTVT FQDERRLIFS SPKYLEIVKM
     FYYAQIRLES EYEMDNNSST SSPNSNNKDK QQKERTKLLC HLLLVSLIGL FDESKKMKNS
     SYNLIAATEA SFGLNFGSHF HRSPEVYVPE DTTTFLGVIG KSLAESNPEL TAYMFIYVLE
     ALKNNVIPHV YIPHTICGLS YWIPNLYQHV YLADDEEGPE NISHIFRILI RLSVRETDFK
     AVYMQYVWLL LLDDGRLTDI IVDEVINHAL ERDSENRDWK KTISLLTVLP TTEVANNIIQ
     KILAKIRSFL PSLKLEAMTQ SWSELTILVK ISIHVFFETS LLVQMYLPEI LFIVSLLIDV
     GPRELRSSLH QLLMNVCHSL AINSALPQDH RNNLDEISDI FAHQKVKFMF GFSEDKGRIL
     QIFSASSFAS KFNILDFFIN NILLLMEYSS TYEANVWKTR YKKYVLESVF TSNSFLSARS
     IMIVGIMGKS YITEGLCKAM LIETMKVIAE PKITDEHLFL AISHIFTYSK IVEGLDPNLD
     LMKHLFWFST LFLESRHPII FEGALLFVSN CIRRLYMAQF ENESETSLIS TLLKGRKFAH
     TFLSKIENLS GIVWNEDNFT HILIFIINKG LSNPFIKSTA FDFLKMMFRN SYFEHQINQK
     SDHYLCYMFL LYFVLNCNQF EELLGDVDFE GEMVNIENKN TIPKILLEWL SSDNENANIT
     LYQGAILFKC SVTDEPSRFR FALIIRHLLT KKPICALRFY SVIRNEIRKI SAFEQNSDCV
     PLAFDILNLL VTHSESNSLE KLHEESIERL TKRGLSIVTS SGIFAKNSDM MIPLDVKPED
     IYERKRIMTM ILSRMSCSA
//