ID   GEA2_YEAST              Reviewed;        1459 AA.
AC   P39993; D3DLM6;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   27-MAR-2024, entry version 194.
DE   RecName: Full=ARF guanine-nucleotide exchange factor 2;
GN   Name=GEA2; OrderedLocusNames=YEL022W;
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 [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   [2]
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   [3]
RP   CHARACTERIZATION.
RX   PubMed=8945477; DOI=10.1038/384479a0;
RA   Peyroche A., Paris S., Jackson C.L.;
RT   "Nucleotide exchange on ARF mediated by yeast Gea1 protein.";
RL   Nature 384:479-481(1996).
RN   [4]
RP   INTERACTION WITH GMH1, AND SUBCELLULAR LOCATION.
RX   PubMed=12808035; DOI=10.1091/mbc.e02-10-0693;
RA   Chantalat S., Courbeyrette R., Senic-Matuglia F., Jackson C.L., Goud B.,
RA   Peyroche A.;
RT   "A novel Golgi membrane protein is a partner of the ARF exchange factors
RT   Gea1p and Gea2p.";
RL   Mol. Biol. Cell 14:2357-2371(2003).
RN   [5]
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   [6]
RP   INTERACTION WITH DRS2, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND
RP   MUTAGENESIS OF VAL-698.
RX   PubMed=14734650; DOI=10.1242/jcs.00896;
RA   Chantalat S., Park S.K., Hua Z., Liu K., Gobin R., Peyroche A.,
RA   Rambourg A., Graham T.R., Jackson C.L.;
RT   "The Arf activator Gea2p and the P-type ATPase Drs2p interact at the Golgi
RT   in Saccharomyces cerevisiae.";
RL   J. Cell Sci. 117:711-722(2004).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND IDENTIFICATION BY
RP   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   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46 AND SER-284, AND
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   [9]
RP   FUNCTION, AND MUTAGENESIS OF VAL-698.
RX   PubMed=19898464; DOI=10.1038/ncb1989;
RA   Natarajan P., Liu K., Patil D.V., Sciorra V.A., Jackson C.L., Graham T.R.;
RT   "Regulation of a Golgi flippase by phosphoinositides and an ArfGEF.";
RL   Nat. Cell Biol. 11:1421-1426(2009).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, 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).
RN   [11]
RP   FUNCTION.
RX   PubMed=25190516; DOI=10.15252/embj.201489039;
RA   Ackema K.B., Hench J., Boeckler S., Wang S.C., Sauder U., Mergentaler H.,
RA   Westermann B., Bard F., Frank S., Spang A.;
RT   "The small GTPase Arf1 modulates mitochondrial morphology and function.";
RL   EMBO J. 33:2659-2675(2014).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 558-766 IN COMPLEX WITH GDP AND
RP   SEC7.
RX   PubMed=11888276; DOI=10.1021/bi012123h;
RA   Renault L., Christova P., Guibert B., Pasqualato S., Cherfils J.;
RT   "Mechanism of domain closure of Sec7 domains and role in BFA sensitivity.";
RL   Biochemistry 41:3605-3612(2002).
CC   -!- FUNCTION: Activates the ARF proteins by exchanging bound GDP for free
CC       GTP. Plays a role in maintaining mitochondrial morphology
CC       (PubMed:25190516). Stimulates DRS2 flippase activity (PubMed:19898464).
CC       {ECO:0000269|PubMed:19898464, ECO:0000269|PubMed:25190516}.
CC   -!- SUBUNIT: Interacts (via SEC7 domain) with DRS2 (via C-terminus); the
CC       interaction is direct (PubMed:14734650). Interacts with GMH1
CC       (PubMed:11888276, PubMed:12808035). {ECO:0000269|PubMed:11888276,
CC       ECO:0000269|PubMed:12808035, ECO:0000269|PubMed:14734650}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12808035,
CC       ECO:0000269|PubMed:14734650}. Membrane {ECO:0000269|PubMed:12808035};
CC       Peripheral membrane protein {ECO:0000269|PubMed:12808035}. Golgi
CC       apparatus membrane {ECO:0000269|PubMed:14734650}; Peripheral membrane
CC       protein {ECO:0000269|PubMed:12808035}. Note=Soluble and partially
CC       membrane-bound (PubMed:12808035, PubMed:14734650). Associates with
CC       early and late Golgi compartments (PubMed:14734650).
CC       {ECO:0000269|PubMed:12808035, ECO:0000269|PubMed:14734650}.
CC   -!- DISRUPTION PHENOTYPE: Exacerbates the cold sensitivity of a DRS2-
CC       knockout. {ECO:0000269|PubMed:14734650}.
CC   -!- MISCELLANEOUS: Present with 7700 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
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DR   EMBL; U18530; AAB64499.1; -; Genomic_DNA.
DR   EMBL; BK006939; DAA07630.1; -; Genomic_DNA.
DR   PIR; S50437; S50437.
DR   RefSeq; NP_010892.1; NM_001178837.1.
DR   PDB; 1KU1; X-ray; 1.93 A; A/B=558-766.
DR   PDB; 7URO; EM; 4.20 A; A/C=1-1459.
DR   PDB; 7URR; EM; 4.70 A; A/B=1-1459.
DR   PDB; 7UT4; EM; 3.90 A; A/B=1-1459.
DR   PDB; 7UTH; EM; 3.90 A; A/B=1-1459.
DR   PDB; 8EZJ; EM; 3.30 A; A/B=1-1459.
DR   PDB; 8EZQ; EM; 3.70 A; A/B=1-1459.
DR   PDBsum; 1KU1; -.
DR   PDBsum; 7URO; -.
DR   PDBsum; 7URR; -.
DR   PDBsum; 7UT4; -.
DR   PDBsum; 7UTH; -.
DR   PDBsum; 8EZJ; -.
DR   PDBsum; 8EZQ; -.
DR   AlphaFoldDB; P39993; -.
DR   EMDB; EMD-28743; -.
DR   EMDB; EMD-28748; -.
DR   SMR; P39993; -.
DR   BioGRID; 36707; 66.
DR   DIP; DIP-6816N; -.
DR   IntAct; P39993; 16.
DR   STRING; 4932.YEL022W; -.
DR   CarbonylDB; P39993; -.
DR   GlyGen; P39993; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; P39993; -.
DR   MaxQB; P39993; -.
DR   PaxDb; 4932-YEL022W; -.
DR   PeptideAtlas; P39993; -.
DR   EnsemblFungi; YEL022W_mRNA; YEL022W; YEL022W.
DR   GeneID; 856691; -.
DR   KEGG; sce:YEL022W; -.
DR   AGR; SGD:S000000748; -.
DR   SGD; S000000748; GEA2.
DR   VEuPathDB; FungiDB:YEL022W; -.
DR   eggNOG; KOG0928; Eukaryota.
DR   GeneTree; ENSGT00940000176690; -.
DR   HOGENOM; CLU_001204_0_1_1; -.
DR   InParanoid; P39993; -.
DR   OMA; ILWTRSP; -.
DR   OrthoDB; 204547at2759; -.
DR   BioCyc; YEAST:G3O-30146-MONOMER; -.
DR   Reactome; R-SCE-199992; trans-Golgi Network Vesicle Budding.
DR   Reactome; R-SCE-5620916; VxPx cargo-targeting to cilium.
DR   Reactome; R-SCE-6807878; COPI-mediated anterograde transport.
DR   Reactome; R-SCE-6811434; COPI-dependent Golgi-to-ER retrograde traffic.
DR   BioGRID-ORCS; 856691; 10 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P39993; -.
DR   PRO; PR:P39993; -.
DR   Proteomes; UP000002311; Chromosome V.
DR   RNAct; P39993; Protein.
DR   GO; GO:0005829; C:cytosol; HDA:SGD.
DR   GO; GO:0000137; C:Golgi cis cisterna; IDA:SGD.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:SGD.
DR   GO; GO:0030036; P:actin cytoskeleton organization; IGI:SGD.
DR   GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IMP:SGD.
DR   GO; GO:0006891; P:intra-Golgi vesicle-mediated transport; IMP:SGD.
DR   GO; GO:0016236; P:macroautophagy; IMP:SGD.
DR   GO; GO:0032012; P:regulation of ARF protein signal transduction; IEA:InterPro.
DR   GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; IGI:SGD.
DR   GO; GO:0033363; P:secretory granule organization; IMP:SGD.
DR   CDD; cd00171; Sec7; 1.
DR   Gene3D; 1.10.220.20; -; 1.
DR   Gene3D; 1.10.1000.11; Arf Nucleotide-binding Site Opener,domain 2; 1.
DR   InterPro; IPR032691; Mon2/Sec7/BIG1-like_HUS.
DR   InterPro; IPR023394; Sec7_C_sf.
DR   InterPro; IPR000904; Sec7_dom.
DR   InterPro; IPR035999; Sec7_dom_sf.
DR   PANTHER; PTHR10663:SF388; GOLGI-SPECIFIC BREFELDIN A-RESISTANCE GUANINE NUCLEOTIDE EXCHANGE FACTOR 1; 1.
DR   PANTHER; PTHR10663; GUANYL-NUCLEOTIDE EXCHANGE FACTOR; 1.
DR   Pfam; PF01369; Sec7; 1.
DR   Pfam; PF12783; Sec7-like_HUS; 1.
DR   SMART; SM00222; Sec7; 1.
DR   SUPFAM; SSF48425; Sec7 domain; 1.
DR   PROSITE; PS50190; SEC7; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Golgi apparatus;
KW   Guanine-nucleotide releasing factor; Membrane; Phosphoprotein;
KW   Reference proteome.
FT   CHAIN           1..1459
FT                   /note="ARF guanine-nucleotide exchange factor 2"
FT                   /id="PRO_0000120213"
FT   DOMAIN          570..714
FT                   /note="SEC7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00189"
FT   REGION          1412..1459
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1443..1459
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         46
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   MOD_RES         284
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17330950,
FT                   ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT   MUTAGEN         698
FT                   /note="V->G: Abolishes interaction with DRS2 and decreases
FT                   DRS2 phosphatidylserine flippase activity in the
FT                   trans-Golgi network membrane. Abnormal secretory vesicle
FT                   formation."
FT                   /evidence="ECO:0000269|PubMed:14734650"
FT   HELIX           558..572
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   HELIX           574..583
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   STRAND          586..588
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   HELIX           592..601
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   TURN            602..605
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   HELIX           608..615
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   HELIX           618..620
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   HELIX           621..629
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   HELIX           638..645
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   TURN            646..648
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   HELIX           655..671
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   HELIX           677..679
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   HELIX           688..690
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   HELIX           695..712
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   HELIX           723..729
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   TURN            730..732
FT                   /evidence="ECO:0007829|PDB:1KU1"
FT   HELIX           741..753
FT                   /evidence="ECO:0007829|PDB:1KU1"
SQ   SEQUENCE   1459 AA;  165668 MW;  99DB9FDD34F863FA CRC64;
     MSDREFVTVD PVTIIIKECI NLSTAMRKYS KFTSQSGVAA LLGGGSEIFS NQDDYLAHTF
     NNLNTNKHND PFLSGFIQLR LMLNKLKNLD NIDSLTILQP FLLIVSTSSI SGYITSLALD
     SLQKFFTLNI INESSQNYIG AHRATVNALT HCRFEGSQQL SDDSVLLKVV FLLRSIVDSP
     YGDLLSNSII YDVLQTILSL ACNNRRSEVL RNAAQSTMIA VTVKIFSKLK TIEPVNVNQI
     YINDESYTND VLKADTIGTN VESKEEGSQE DPIGMKVNNE EAISEDDGIE EEHIHSEKST
     NGAEQLDIVQ KTTRSNSRIQ AYADDNYGLP VVRQYLNLLL SLIAPENELK HSYSTRIFGL
     ELIQTALEIS GDRLQLYPRL FTLISDPIFK SILFIIQNTT KLSLLQATLQ LFTTLVVILG
     NNLQLQIELT LTRIFSILLD DGTANNSSSE NKNKPSIIKE LLIEQISILW TRSPSFFTST
     FINFDCNLDR ADVSINFLKA LTKLALPESA LTTTESVPPI CLEGLVSLVD DMFDHMKDID
     REEFGRQKNE MEILKKRDRK TEFIECTNAF NEKPKKGIPM LIEKGFIASD SDKDIAEFLF
     NNNNRMNKKT IGLLLCHPDK VSLLNEYIRL FDFSGLRVDE AIRILLTKFR LPGESQQIER
     IIEAFSSAYC ENQDYDPSKI SDNAEDDIST VQPDADSVFI LSYSIIMLNT DLHNPQVKEH
     MSFEDYSGNL KGCCNHKDFP FWYLDRIYCS IRDKEIVMPE EHHGNEKWFE DAWNNLISST
     TVITEIKKDT QSVMDKLTPL ELLNFDRAIF KQVGPSIVST LFNIYVVASD DHISTRMITS
     LDKCSYISAF FDFKDLFNDI LNSIAKGTTL INSSHDDELS TLAFEYGPMP LVQIKFEDTN
     TEIPVSTDAV RFGRSFKGQL NTVVFFRIIR RNKDPKIFSK ELWLNIVNII LTLYEDLILS
     PDIFPDLQKR LKLSNLPKPS PEISINKSKE SKGLLSTFAS YLKGDEEPTE EEIKSSKKAM
     ECIKSSNIAA SVFGNESNIT ADLIKTLLDS AKTEKNADNS RYFEAELLFI IELTIALFLF
     CKEEKELGKF ILQKVFQLSH TKGLTKRTVR RMLTYKILLI SLCADQTEYL SKLINDELLK
     KGDIFTQKFF ATNQGKEFLK RLFSLTESEF YRGFLLGNEN FWKFLRKVTA MKEQSESIFE
     YLNESIKTDS NILTNENFMW VLGLLDEISS MGAVGNHWEI EYKKLTESGH KIDKENPYKK
     SIELSLKSIQ LTSHLLEDNN DLRKNEIFAI IQALAHQCIN PCKQISEFAV VTLEQTLINK
     IEIPTNEMES VEELIEGGLL PLLNSSETQE DQKILISSIL TIISNVYLHY LKLGKTSNET
     FLKILSIFNK FVEDSDIEKK LQQLILDKKS IEKGNGSSSH GSAHEQTPES NDVEIEATAP
     IDDNTDDDNK PKLSDVEKD
//