ID   GEF1_YEAST              Reviewed;         779 AA.
AC   P37020; D6VWL1;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   05-OCT-2010, sequence version 2.
DT   27-MAR-2024, entry version 203.
DE   RecName: Full=Anion/proton exchange transporter GEF1;
DE   AltName: Full=CLC protein GEF1;
DE   AltName: Full=ClC-A;
DE   AltName: Full=ClC-Y1;
DE   AltName: Full=Voltage-gated chloride channel;
DE   Contains:
DE     RecName: Full=GEF1 N-terminal;
DE   Contains:
DE     RecName: Full=GEF1 C-terminal;
DE   Flags: Precursor;
GN   Name=GEF1; Synonyms=CLCY1; OrderedLocusNames=YJR040W; ORFNames=J1616;
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], AND FUNCTION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=7505388; DOI=10.1007/bf00279896;
RA   Greene J.R., Brown N.H., Didomenico B.J., Kaplan J., Eide D.J.;
RT   "The GEF1 gene of Saccharomyces cerevisiae encodes an integral membrane
RT   protein; mutations in which have effects on respiration and iron-limited
RT   growth.";
RL   Mol. Gen. Genet. 241:542-553(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=7932715; DOI=10.1006/jmbi.1994.1607;
RA   Huang M.-E., Chuat J.-C., Galibert F.;
RT   "A voltage-gated chloride channel in the yeast Saccharomyces cerevisiae.";
RL   J. Mol. Biol. 242:595-598(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=7668047; DOI=10.1002/yea.320110809;
RA   Huang M.-E., Chuat J.-C., Galibert F.;
RT   "Analysis of a 42.5 kb DNA sequence of chromosome X reveals three tRNA
RT   genes and 14 new open reading frames including a gene most probably
RT   belonging to the family of ubiquitin-protein ligases.";
RL   Yeast 11:775-781(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA   Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA   Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA   Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA   Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA   Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA   Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA   Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA   Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA   To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA   von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT   "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL   EMBO J. 15:2031-2049(1996).
RN   [5]
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   [6]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=9614122; DOI=10.1074/jbc.273.24.15110;
RA   Schwappach B., Stobrawa S., Hechenberger M., Steinmeyer K., Jentsch T.J.;
RT   "Golgi localization and functionally important domains in the NH2 and COOH
RT   terminus of the yeast CLC putative chloride channel Gef1p.";
RL   J. Biol. Chem. 273:15110-15118(1998).
RN   [7]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=9520490; DOI=10.1073/pnas.95.7.4046;
RA   Gaxiola R.A., Yuan D.S., Klausner R.D., Fink G.R.;
RT   "The yeast CLC chloride channel functions in cation homeostasis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:4046-4050(1998).
RN   [8]
RP   FUNCTION.
RX   PubMed=12074596; DOI=10.1016/s0006-291x(02)00610-1;
RA   Flis K., Bednarczyk P., Hordejuk R., Szewczyk A., Berest V., Dolowy K.,
RA   Edelman A., Kurlandzka A.;
RT   "The Gef1 protein of Saccharomyces cerevisiae is associated with chloride
RT   channel activity.";
RL   Biochem. Biophys. Res. Commun. 294:1144-1150(2002).
RN   [9]
RP   CLEAVAGE BY KEX2, AND SUBCELLULAR LOCATION.
RX   PubMed=15710404; DOI=10.1016/j.febslet.2005.01.011;
RA   Wachter A., Schwappach B.;
RT   "The yeast CLC chloride channel is proteolytically processed by the furin-
RT   like protease Kex2p in the first extracellular loop.";
RL   FEBS Lett. 579:1149-1153(2005).
RN   [10]
RP   INTERACTION WITH GET3.
RX   PubMed=16260785; DOI=10.1074/jbc.m507481200;
RA   Metz J., Waechter A., Schmidt B., Bujnicki J.M., Schwappach B.;
RT   "The yeast Arr4p ATPase binds the chloride transporter Gef1p when copper is
RT   available in the cytosol.";
RL   J. Biol. Chem. 281:410-417(2006).
RN   [11]
RP   TOPOLOGY [LARGE SCALE ANALYSIS].
RC   STRAIN=ATCC 208353 / W303-1A;
RX   PubMed=16847258; DOI=10.1073/pnas.0604075103;
RA   Kim H., Melen K., Oesterberg M., von Heijne G.;
RT   "A global topology map of the Saccharomyces cerevisiae membrane proteome.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
RN   [12]
RP   FUNCTION.
RX   PubMed=17662057; DOI=10.1111/j.1567-1364.2007.00279.x;
RA   Lopez-Rodriguez A., Trejo A.C., Coyne L., Halliwell R.F., Miledi R.,
RA   Martinez-Torres A.;
RT   "The product of the gene GEF1 of Saccharomyces cerevisiae transports
RT   Cl- across the plasma membrane.";
RL   FEMS Yeast Res. 7:1218-1229(2007).
CC   -!- FUNCTION: Anion/proton exchange transporter involved in iron and copper
CC       cation homeostasis. Involved in intracellular iron metabolism during
CC       growth on fermentable and non fermentable carbon sources. Required for
CC       proper copper-loading and maturation of multicopper oxidase FET3.
CC       Important for adjusting intracellular compartment pH to more alkaline
CC       pH under iron limitation. May also transport chloride ions through the
CC       plasma membrane. {ECO:0000269|PubMed:12074596,
CC       ECO:0000269|PubMed:17662057, ECO:0000269|PubMed:7505388,
CC       ECO:0000269|PubMed:9520490, ECO:0000269|PubMed:9614122}.
CC   -!- SUBUNIT: Homodimer (By similarity). Interacts with GET3. {ECO:0000250,
CC       ECO:0000269|PubMed:16260785}.
CC   -!- INTERACTION:
CC       P37020; Q12154: GET3; NbExp=6; IntAct=EBI-7552, EBI-2989;
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC       {ECO:0000269|PubMed:9614122}; Multi-pass membrane protein
CC       {ECO:0000255}. Endosome membrane {ECO:0000305|PubMed:9520490}; Multi-
CC       pass membrane protein {ECO:0000255}. Prevacuolar compartment membrane
CC       {ECO:0000269|PubMed:12074596}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- PTM: Proteolytically processed in the secretory pathway by protease
CC       KEX2 within the first extracellular loop. However, both the N- and C-
CC       terminal products of the cleavage reaction are required for assembly of
CC       a functional channel. {ECO:0000269|PubMed:15710404}.
CC   -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family.
CC       {ECO:0000305}.
CC   -!- CAUTION: Was originally thought to be a voltage-gated ClC-type chloride
CC       channel. {ECO:0000305}.
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DR   EMBL; Z23117; CAA80663.1; -; Genomic_DNA.
DR   EMBL; L29347; AAA53399.1; -; Genomic_DNA.
DR   EMBL; Z49540; CAA89567.1; -; Genomic_DNA.
DR   EMBL; L36344; AAA88741.1; -; Genomic_DNA.
DR   EMBL; BK006943; DAA08827.1; -; Genomic_DNA.
DR   PIR; S50054; S50054.
DR   RefSeq; NP_012574.1; NM_001181698.1.
DR   AlphaFoldDB; P37020; -.
DR   SMR; P37020; -.
DR   BioGRID; 33791; 123.
DR   DIP; DIP-3949N; -.
DR   IntAct; P37020; 7.
DR   MINT; P37020; -.
DR   STRING; 4932.YJR040W; -.
DR   TCDB; 2.A.49.1.1; the chloride carrier/channel (clc) family.
DR   iPTMnet; P37020; -.
DR   MaxQB; P37020; -.
DR   PaxDb; 4932-YJR040W; -.
DR   PeptideAtlas; P37020; -.
DR   EnsemblFungi; YJR040W_mRNA; YJR040W; YJR040W.
DR   GeneID; 853497; -.
DR   KEGG; sce:YJR040W; -.
DR   AGR; SGD:S000003801; -.
DR   SGD; S000003801; GEF1.
DR   VEuPathDB; FungiDB:YJR040W; -.
DR   eggNOG; KOG0475; Eukaryota.
DR   HOGENOM; CLU_003181_2_2_1; -.
DR   InParanoid; P37020; -.
DR   OMA; FLKINMT; -.
DR   OrthoDB; 150430at2759; -.
DR   BioCyc; YEAST:G3O-31675-MONOMER; -.
DR   Reactome; R-SCE-2672351; Stimuli-sensing channels.
DR   BioGRID-ORCS; 853497; 7 hits in 10 CRISPR screens.
DR   PRO; PR:P37020; -.
DR   Proteomes; UP000002311; Chromosome X.
DR   RNAct; P37020; Protein.
DR   GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR   GO; GO:0005769; C:early endosome; IBA:GO_Central.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR   GO; GO:0005768; C:endosome; IDA:SGD.
DR   GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0000324; C:fungal-type vacuole; IDA:SGD.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:SGD.
DR   GO; GO:0005797; C:Golgi medial cisterna; IDA:SGD.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IDA:SGD.
DR   GO; GO:0005247; F:voltage-gated chloride channel activity; IDA:SGD.
DR   GO; GO:0006878; P:intracellular copper ion homeostasis; IMP:SGD.
DR   GO; GO:0006879; P:intracellular iron ion homeostasis; IMP:SGD.
DR   GO; GO:0034756; P:regulation of iron ion transport; IMP:CACAO.
DR   CDD; cd04591; CBS_pair_voltage-gated_CLC_euk_bac; 1.
DR   CDD; cd03684; ClC_3_like; 1.
DR   Gene3D; 3.10.580.10; CBS-domain; 1.
DR   Gene3D; 1.10.3080.10; Clc chloride channel; 1.
DR   InterPro; IPR000644; CBS_dom.
DR   InterPro; IPR046342; CBS_dom_sf.
DR   InterPro; IPR014743; Cl-channel_core.
DR   InterPro; IPR001807; Cl-channel_volt-gated.
DR   PANTHER; PTHR45711:SF9; ANION_PROTON EXCHANGE TRANSPORTER GEF1; 1.
DR   PANTHER; PTHR45711; CHLORIDE CHANNEL PROTEIN; 1.
DR   Pfam; PF00571; CBS; 1.
DR   Pfam; PF00654; Voltage_CLC; 1.
DR   PRINTS; PR00762; CLCHANNEL.
DR   SMART; SM00116; CBS; 2.
DR   SUPFAM; SSF54631; CBS-domain pair; 1.
DR   SUPFAM; SSF81340; Clc chloride channel; 1.
DR   PROSITE; PS51371; CBS; 2.
PE   1: Evidence at protein level;
KW   CBS domain; Chloride; Chloride channel; Endosome; Golgi apparatus;
KW   Ion channel; Ion transport; Membrane; Reference proteome; Repeat;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..779
FT                   /note="Anion/proton exchange transporter GEF1"
FT                   /id="PRO_0000094472"
FT   CHAIN           1..136
FT                   /note="GEF1 N-terminal"
FT                   /id="PRO_0000419270"
FT   CHAIN           137..779
FT                   /note="GEF1 C-terminal"
FT                   /id="PRO_0000419271"
FT   TOPO_DOM        1..75
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        76..96
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        97..154
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        155..175
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        176..177
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        178..198
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        199..203
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        204..224
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        225..264
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        265..285
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        286..296
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        297..319
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        320..336
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        337..357
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        358..369
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        370..390
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        391..436
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        437..457
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        458..465
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        466..486
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        487..500
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        501..523
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        524..529
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        530..552
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        553..779
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          591..659
FT                   /note="CBS 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT   DOMAIN          688..744
FT                   /note="CBS 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT   SITE            136..137
FT                   /note="Cleavage; by KEX2"
FT   SITE            230
FT                   /note="Mediates proton transfer from the outer aqueous
FT                   phase to the interior of the protein; involved in linking
FT                   H(+) and Cl(-) transport"
FT                   /evidence="ECO:0000250"
FT   SITE            287
FT                   /note="Mediates proton transfer from the protein to the
FT                   inner aqueous phase"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        13
FT                   /note="G -> R (in Ref. 1; CAA80663)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        207
FT                   /note="F -> L (in Ref. 1; CAA80663)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        257
FT                   /note="S -> T (in Ref. 1; CAA80663)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        262
FT                   /note="I -> L (in Ref. 1; CAA80663)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        497
FT                   /note="T -> I (in Ref. 1; CAA80663)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   779 AA;  87592 MW;  544C751402D32E19 CRC64;
     MPTTYVPINQ PIGDGEDVID TNRFTNIPET QNFDQFVTID KIAEENRPLS VDSDREFLNS
     KYRHYREVIW DRAKTFITLS STAIVIGCIA GFLQVFTETL VNWKTGHCQR NWLLNKSFCC
     NGVVNEVTST SNLLLKRQEF ECEAQGLWIA WKGHVSPFII FMLLSVLFAL ISTLLVKYVA
     PMATGSGISE IKVWVSGFEY NKEFLGFLTL VIKSVALPLA ISSGLSVGKE GPSVHYATCC
     GYLLTKWLLR DTLTYSSQYE YITAASGAGV AVAFGAPIGG VLFGLEEIAS ANRFNSSTLW
     KSYYVALVAI TTLKYIDPFR NGRVILFNVT YDRDWKVQEI PIFIALGIFG GLYGKYISKW
     NINFIHFRKM YLSSWPVQEV LFLATLTALI SYFNEFLKLD MTESMGILFH ECVKNDNTST
     FSHRLCQLDE NTHAFEFLKI FTSLCFATVI RALLVVVSYG ARVPAGIFVP SMAVGATFGR
     AVSLLVERFI SGPSVITPGA YAFLGAAATL SGITNLTLTV VVIMFELTGA FMYIIPLMIV
     VAITRIILST SGISGGIADQ MIMVNGFPYL EDEQDEEEEE TLEKYTAEQL MSSKLITINE
     TIYLSELESL LYDSASEYSV HGFPITKDED KFEKEKRCIG YVLKRHLASK IMMQSVNSTK
     AQTTLVYFNK SNEELGHREN CIGFKDIMNE SPISVKKAVP VTLLFRMFKE LGCKTIIVEE
     SGILKGLVTA KDILRFKRIK YREVHGAKFT YNEALDRRCW SVIHFIIKRF TTNRNGNVI
//