GEF1_YEAST
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 03-AUG-2022, entry version 196.
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; 122.
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; P37020; -.
DR PRIDE; P37020; -.
DR EnsemblFungi; YJR040W_mRNA; YJR040W; YJR040W.
DR GeneID; 853497; -.
DR KEGG; sce:YJR040W; -.
DR SGD; S000003801; GEF1.
DR VEuPathDB; FungiDB:YJR040W; -.
DR eggNOG; KOG0475; Eukaryota.
DR HOGENOM; CLU_003181_2_2_1; -.
DR InParanoid; P37020; -.
DR OMA; IMHLTIS; -.
DR BioCyc; YEAST:G3O-31675-MON; -.
DR Reactome; R-SCE-2672351; Stimuli-sensing channels.
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:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:SGD.
DR GO; GO:0015299; F:solute:proton antiporter activity; IBA:GO_Central.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; IDA:SGD.
DR GO; GO:0006878; P:cellular copper ion homeostasis; IMP:SGD.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:SGD.
DR GO; GO:0034756; P:regulation of iron ion transport; IMP:CACAO.
DR Gene3D; 3.10.580.10; -; 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 Pfam; PF00571; CBS; 2.
DR Pfam; PF00654; Voltage_CLC; 1.
DR PRINTS; PR00762; CLCHANNEL.
DR SMART; SM00116; CBS; 2.
DR SUPFAM; SSF54631; SSF54631; 1.
DR SUPFAM; SSF81340; SSF81340; 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
