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Protein

Anion/proton exchange transporter GEF1

Gene

GEF1

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Anion/proton exchange transporter involved in iron and copper cation homeostasis. Involved in intracellular iron metabolism during growth on fermentable and non fermentable carbon sources. Required for proper copper-loading and maturation of multicopper oxidase FET3. Important for adjusting intracellular compartment pH to more alkaline pH under iron limitation. May also transport chloride ions through the plasma membrane.5 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei136 – 1372Cleavage; by KEX2
Sitei230 – 2301Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H(+) and Cl(-) transportBy similarity
Sitei287 – 2871Mediates proton transfer from the protein to the inner aqueous phaseBy similarity

GO - Molecular functioni

  1. adenyl nucleotide binding Source: InterPro
  2. voltage-gated chloride channel activity Source: SGD

GO - Biological processi

  1. cellular copper ion homeostasis Source: SGD
  2. cellular iron ion homeostasis Source: SGD
  3. regulation of anion transport Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Chloride channel, Ion channel

Keywords - Biological processi

Ion transport, Transport

Keywords - Ligandi

Chloride

Enzyme and pathway databases

BioCyciYEAST:G3O-31675-MONOMER.
ReactomeiREACT_204366. Stimuli-sensing channels.

Protein family/group databases

TCDBi2.A.49.1.1. the chloride carrier/channel (clc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Anion/proton exchange transporter GEF1
Alternative name(s):
CLC protein GEF1
ClC-A
ClC-Y1
Voltage-gated chloride channel
Cleaved into the following 2 chains:
Gene namesi
Name:GEF1
Synonyms:CLCY1
Ordered Locus Names:YJR040W
ORF Names:J1616
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
ProteomesiUP000002311: Chromosome X

Organism-specific databases

SGDiS000003801. GEF1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 7575CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei76 – 9621HelicalSequence AnalysisAdd
BLAST
Topological domaini97 – 15458LumenalSequence AnalysisAdd
BLAST
Transmembranei155 – 17521HelicalSequence AnalysisAdd
BLAST
Topological domaini176 – 1772CytoplasmicSequence Analysis
Transmembranei178 – 19821HelicalSequence AnalysisAdd
BLAST
Topological domaini199 – 2035LumenalSequence Analysis
Transmembranei204 – 22421HelicalSequence AnalysisAdd
BLAST
Topological domaini225 – 26440CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei265 – 28521HelicalSequence AnalysisAdd
BLAST
Topological domaini286 – 29611LumenalSequence AnalysisAdd
BLAST
Transmembranei297 – 31923HelicalSequence AnalysisAdd
BLAST
Topological domaini320 – 33617CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei337 – 35721HelicalSequence AnalysisAdd
BLAST
Topological domaini358 – 36912LumenalSequence AnalysisAdd
BLAST
Transmembranei370 – 39021HelicalSequence AnalysisAdd
BLAST
Topological domaini391 – 43646CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei437 – 45721HelicalSequence AnalysisAdd
BLAST
Topological domaini458 – 4658LumenalSequence Analysis
Transmembranei466 – 48621HelicalSequence AnalysisAdd
BLAST
Topological domaini487 – 50014CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei501 – 52323HelicalSequence AnalysisAdd
BLAST
Topological domaini524 – 5296LumenalSequence Analysis
Transmembranei530 – 55223HelicalSequence AnalysisAdd
BLAST
Topological domaini553 – 779227CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. chloride channel complex Source: UniProtKB-KW
  2. endoplasmic reticulum Source: SGD
  3. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  4. endosome Source: SGD
  5. endosome membrane Source: UniProtKB-SubCell
  6. fungal-type vacuole Source: SGD
  7. Golgi apparatus Source: SGD
  8. Golgi medial cisterna Source: SGD
  9. Golgi membrane Source: UniProtKB-SubCell
  10. plasma membrane Source: SGD
  11. vacuolar membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane, Vacuole

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 779779Anion/proton exchange transporter GEF1PRO_0000094472Add
BLAST
Chaini1 – 136136GEF1 N-terminalPRO_0000419270Add
BLAST
Chaini137 – 779643GEF1 C-terminalPRO_0000419271Add
BLAST

Post-translational modificationi

Proteolytically processed in the secretory pathway by protease KEX2 within the first extracellular loop. However, both the N- and C-terminal products of the cleavage reaction are required for assembly of a functional channel.1 Publication

Proteomic databases

MaxQBiP37020.
PaxDbiP37020.

Expressioni

Gene expression databases

GenevestigatoriP37020.

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with GET3.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
GET3Q121546EBI-7552,EBI-2989

Protein-protein interaction databases

BioGridi33791. 67 interactions.
DIPiDIP-3949N.
IntActiP37020. 6 interactions.
MINTiMINT-492781.
STRINGi4932.YJR040W.

Structurei

3D structure databases

ProteinModelPortaliP37020.
SMRiP37020. Positions 153-570, 596-735.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini591 – 65969CBS 1PROSITE-ProRule annotationAdd
BLAST
Domaini688 – 74457CBS 2PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 2 CBS domains.PROSITE-ProRule annotation

Keywords - Domaini

CBS domain, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0038.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000164493.
InParanoidiP37020.
KOiK05012.
OMAiDENTHAF.
OrthoDBiEOG72RN6P.

Family and domain databases

Gene3Di1.10.3080.10. 2 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
[Graphical view]
PfamiPF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 3 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P37020-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MPTTYVPINQ PIGDGEDVID TNRFTNIPET QNFDQFVTID KIAEENRPLS
60 70 80 90 100
VDSDREFLNS KYRHYREVIW DRAKTFITLS STAIVIGCIA GFLQVFTETL
110 120 130 140 150
VNWKTGHCQR NWLLNKSFCC NGVVNEVTST SNLLLKRQEF ECEAQGLWIA
160 170 180 190 200
WKGHVSPFII FMLLSVLFAL ISTLLVKYVA PMATGSGISE IKVWVSGFEY
210 220 230 240 250
NKEFLGFLTL VIKSVALPLA ISSGLSVGKE GPSVHYATCC GYLLTKWLLR
260 270 280 290 300
DTLTYSSQYE YITAASGAGV AVAFGAPIGG VLFGLEEIAS ANRFNSSTLW
310 320 330 340 350
KSYYVALVAI TTLKYIDPFR NGRVILFNVT YDRDWKVQEI PIFIALGIFG
360 370 380 390 400
GLYGKYISKW NINFIHFRKM YLSSWPVQEV LFLATLTALI SYFNEFLKLD
410 420 430 440 450
MTESMGILFH ECVKNDNTST FSHRLCQLDE NTHAFEFLKI FTSLCFATVI
460 470 480 490 500
RALLVVVSYG ARVPAGIFVP SMAVGATFGR AVSLLVERFI SGPSVITPGA
510 520 530 540 550
YAFLGAAATL SGITNLTLTV VVIMFELTGA FMYIIPLMIV VAITRIILST
560 570 580 590 600
SGISGGIADQ MIMVNGFPYL EDEQDEEEEE TLEKYTAEQL MSSKLITINE
610 620 630 640 650
TIYLSELESL LYDSASEYSV HGFPITKDED KFEKEKRCIG YVLKRHLASK
660 670 680 690 700
IMMQSVNSTK AQTTLVYFNK SNEELGHREN CIGFKDIMNE SPISVKKAVP
710 720 730 740 750
VTLLFRMFKE LGCKTIIVEE SGILKGLVTA KDILRFKRIK YREVHGAKFT
760 770
YNEALDRRCW SVIHFIIKRF TTNRNGNVI
Length:779
Mass (Da):87,592
Last modified:October 5, 2010 - v2
Checksum:i544C751402D32E19
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti13 – 131G → R in CAA80663. (PubMed:7505388)Curated
Sequence conflicti207 – 2071F → L in CAA80663. (PubMed:7505388)Curated
Sequence conflicti257 – 2571S → T in CAA80663. (PubMed:7505388)Curated
Sequence conflicti262 – 2621I → L in CAA80663. (PubMed:7505388)Curated
Sequence conflicti497 – 4971T → I in CAA80663. (PubMed:7505388)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z23117 Genomic DNA. Translation: CAA80663.1.
L29347 Genomic DNA. Translation: AAA53399.1.
Z49540 Genomic DNA. Translation: CAA89567.1.
L36344 Genomic DNA. Translation: AAA88741.1.
BK006943 Genomic DNA. Translation: DAA08827.1.
PIRiS50054.
RefSeqiNP_012574.1. NM_001181698.1.

Genome annotation databases

EnsemblFungiiYJR040W; YJR040W; YJR040W.
GeneIDi853497.
KEGGisce:YJR040W.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z23117 Genomic DNA. Translation: CAA80663.1.
L29347 Genomic DNA. Translation: AAA53399.1.
Z49540 Genomic DNA. Translation: CAA89567.1.
L36344 Genomic DNA. Translation: AAA88741.1.
BK006943 Genomic DNA. Translation: DAA08827.1.
PIRiS50054.
RefSeqiNP_012574.1. NM_001181698.1.

3D structure databases

ProteinModelPortaliP37020.
SMRiP37020. Positions 153-570, 596-735.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi33791. 67 interactions.
DIPiDIP-3949N.
IntActiP37020. 6 interactions.
MINTiMINT-492781.
STRINGi4932.YJR040W.

Protein family/group databases

TCDBi2.A.49.1.1. the chloride carrier/channel (clc) family.

Proteomic databases

MaxQBiP37020.
PaxDbiP37020.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYJR040W; YJR040W; YJR040W.
GeneIDi853497.
KEGGisce:YJR040W.

Organism-specific databases

SGDiS000003801. GEF1.

Phylogenomic databases

eggNOGiCOG0038.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000164493.
InParanoidiP37020.
KOiK05012.
OMAiDENTHAF.
OrthoDBiEOG72RN6P.

Enzyme and pathway databases

BioCyciYEAST:G3O-31675-MONOMER.
ReactomeiREACT_204366. Stimuli-sensing channels.

Miscellaneous databases

NextBioi974134.

Gene expression databases

GenevestigatoriP37020.

Family and domain databases

Gene3Di1.10.3080.10. 2 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
[Graphical view]
PfamiPF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 3 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The GEF1 gene of Saccharomyces cerevisiae encodes an integral membrane protein; mutations in which have effects on respiration and iron-limited growth."
    Greene J.R., Brown N.H., Didomenico B.J., Kaplan J., Eide D.J.
    Mol. Gen. Genet. 241:542-553(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION.
    Strain: ATCC 204508 / S288c.
  2. "A voltage-gated chloride channel in the yeast Saccharomyces cerevisiae."
    Huang M.-E., Chuat J.-C., Galibert F.
    J. Mol. Biol. 242:595-598(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  3. "Analysis of a 42.5 kb DNA sequence of chromosome X reveals three tRNA genes and 14 new open reading frames including a gene most probably belonging to the family of ubiquitin-protein ligases."
    Huang M.-E., Chuat J.-C., Galibert F.
    Yeast 11:775-781(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  4. "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X."
    Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C., Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D., Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J., Heumann K.
    , Hilger F., Hollenberg C.P., Huang M.-E., Jacq C., Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E., Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T., Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R., Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N., To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H., von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.
    EMBO J. 15:2031-2049(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  5. Cited for: GENOME REANNOTATION.
    Strain: ATCC 204508 / S288c.
  6. "Golgi localization and functionally important domains in the NH2 and COOH terminus of the yeast CLC putative chloride channel Gef1p."
    Schwappach B., Stobrawa S., Hechenberger M., Steinmeyer K., Jentsch T.J.
    J. Biol. Chem. 273:15110-15118(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  7. "The yeast CLC chloride channel functions in cation homeostasis."
    Gaxiola R.A., Yuan D.S., Klausner R.D., Fink G.R.
    Proc. Natl. Acad. Sci. U.S.A. 95:4046-4050(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  8. "The Gef1 protein of Saccharomyces cerevisiae is associated with chloride channel activity."
    Flis K., Bednarczyk P., Hordejuk R., Szewczyk A., Berest V., Dolowy K., Edelman A., Kurlandzka A.
    Biochem. Biophys. Res. Commun. 294:1144-1150(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "The yeast CLC chloride channel is proteolytically processed by the furin-like protease Kex2p in the first extracellular loop."
    Wachter A., Schwappach B.
    FEBS Lett. 579:1149-1153(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY KEX2, SUBCELLULAR LOCATION.
  10. "The yeast Arr4p ATPase binds the chloride transporter Gef1p when copper is available in the cytosol."
    Metz J., Waechter A., Schmidt B., Bujnicki J.M., Schwappach B.
    J. Biol. Chem. 281:410-417(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GET3.
  11. "A global topology map of the Saccharomyces cerevisiae membrane proteome."
    Kim H., Melen K., Oesterberg M., von Heijne G.
    Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY [LARGE SCALE ANALYSIS].
    Strain: ATCC 208353 / W303-1A.
  12. "The product of the gene GEF1 of Saccharomyces cerevisiae transports Cl- across the plasma membrane."
    Lopez-Rodriguez A., Trejo A.C., Coyne L., Halliwell R.F., Miledi R., Martinez-Torres A.
    FEMS Yeast Res. 7:1218-1229(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiGEF1_YEAST
AccessioniPrimary (citable) accession number: P37020
Secondary accession number(s): D6VWL1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: October 5, 2010
Last modified: January 7, 2015
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Caution

Was originally thought to be a voltage-gated ClC-type chloride channel.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  3. Yeast chromosome X
    Yeast (Saccharomyces cerevisiae) chromosome X: entries and gene names

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.