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Protein

Glutathione-regulated potassium-efflux system protein KefC

Gene

kefC

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Pore-forming subunit of a potassium efflux system that confers protection against electrophiles. Catalyzes K+/H+ antiport. Can also export rubidium, lithium and sodium.UniRule annotation3 Publications

Enzyme regulationi

Inhibited by glutathione. This inhibition is increased by NADH. Activated by adducts between glutathione and electrophiles.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei412 – 4121Glutathione; shared with dimeric partner
Binding sitei434 – 4341AMP1 Publication
Binding sitei472 – 4721AMP1 Publication
Binding sitei496 – 4961AMP1 Publication
Binding sitei516 – 5161Glutathione

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi408 – 4103AMP1 Publication
Nucleotide bindingi429 – 4302AMP1 Publication
Nucleotide bindingi449 – 4502AMP1 Publication

GO - Molecular functioni

  • enzyme binding Source: EcoCyc
  • glutathione-regulated potassium exporter activity Source: EcoCyc
  • nucleotide binding Source: UniProtKB-KW
  • solute:proton antiporter activity Source: InterPro
  • toxic substance binding Source: EcoCyc

GO - Biological processi

  • potassium ion transport Source: EcoliWiki
  • regulation of pH Source: EcoliWiki
  • response to methylglyoxal Source: EcoCyc
  • response to toxic substance Source: EcoCyc
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Potassium transport, Transport

Keywords - Ligandi

Nucleotide-binding, Potassium

Enzyme and pathway databases

BioCyciEcoCyc:KEFC-MONOMER.
ECOL316407:JW0046-MONOMER.
MetaCyc:KEFC-MONOMER.

Protein family/group databases

TCDBi2.A.37.1.1. the monovalent cation:proton antiporter-2 (cpa2) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Glutathione-regulated potassium-efflux system protein KefCUniRule annotation
Alternative name(s):
K(+)/H(+) antiporterUniRule annotation
Gene namesi
Name:kefCUniRule annotation
Synonyms:trkC
Ordered Locus Names:b0047, JW0046
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10521. kefC.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 33PeriplasmicSequence analysis
Transmembranei4 – 2421HelicalUniRule annotationAdd
BLAST
Topological domaini25 – 251CytoplasmicSequence analysis
Transmembranei26 – 4621HelicalUniRule annotationAdd
BLAST
Topological domaini47 – 537PeriplasmicSequence analysis
Transmembranei54 – 7421HelicalUniRule annotationAdd
BLAST
Topological domaini75 – 8915CytoplasmicSequence analysisAdd
BLAST
Transmembranei90 – 11021HelicalUniRule annotationAdd
BLAST
Topological domaini111 – 1133PeriplasmicSequence analysis
Transmembranei114 – 13421HelicalUniRule annotationAdd
BLAST
Topological domaini135 – 14814CytoplasmicSequence analysisAdd
BLAST
Transmembranei149 – 16921HelicalUniRule annotationAdd
BLAST
Topological domaini170 – 1778PeriplasmicSequence analysis
Transmembranei178 – 19821HelicalUniRule annotationAdd
BLAST
Topological domaini199 – 21315CytoplasmicSequence analysisAdd
BLAST
Transmembranei214 – 23320HelicalUniRule annotationAdd
BLAST
Topological domaini234 – 2363PeriplasmicSequence analysis
Transmembranei237 – 25418HelicalUniRule annotationAdd
BLAST
Topological domaini255 – 26915CytoplasmicSequence analysisAdd
BLAST
Transmembranei270 – 29021HelicalUniRule annotationAdd
BLAST
Topological domaini291 – 2933PeriplasmicSequence analysis
Transmembranei294 – 31421HelicalUniRule annotationAdd
BLAST
Topological domaini315 – 32612CytoplasmicSequence analysisAdd
BLAST
Transmembranei327 – 34721HelicalUniRule annotationAdd
BLAST
Topological domaini348 – 35811PeriplasmicSequence analysisAdd
BLAST
Transmembranei359 – 37921HelicalUniRule annotationAdd
BLAST
Topological domaini380 – 620241Cytoplasmic1 PublicationAdd
BLAST

GO - Cellular componenti

  • integral component of plasma membrane Source: EcoliWiki
  • membrane Source: EcoCyc
  • plasma membrane Source: EcoCyc
Complete GO annotation...

Keywords - Cellular componenti

Cell inner membrane, Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi262 – 2621E → K: Increases potassium efflux in the absence of glutathione, but not in the presence of glutathione. Increases constitutive potassium efflux; when associated with D-551.
Mutagenesisi264 – 2641D → A: Increases constitutive potassium efflux. 1 Publication
Mutagenesisi412 – 4121Q → A: Increases constitutive potassium efflux and reduces glutathione-mediated inhibition of potassium efflux. 1 Publication
Mutagenesisi412 – 4121Q → K: Increases constitutive potassium efflux and abolishes regulation of potassium efflux by glutathione and glutathione adducts. 1 Publication
Mutagenesisi416 – 4161R → A: Increases constitutive potassium efflux and abolishes regulation of potassium efflux by glutathione and glutathione adducts; when associated with A-516 and A-551. 2 Publications
Mutagenesisi416 – 4161R → S: Increased constitutive potassium efflux. 2 Publications
Mutagenesisi441 – 4411F → D or L: Reduced activation of potassium efflux by glutathione adducts. 1 Publication
Mutagenesisi441 – 4411F → W or Y: No effect on activation of potassium efflux by glutathione adducts. 1 Publication
Mutagenesisi499 – 4991D → A: Strongly reduced activation of potassium efflux by glutathione adducts. 1 Publication
Mutagenesisi499 – 4991D → G: Mildly reduced activation of potassium efflux by glutathione adducts. 1 Publication
Mutagenesisi499 – 4991D → S: No effect on potassium efflux. 1 Publication
Mutagenesisi516 – 5161R → A: Increases constitutive potassium efflux and abolishes regulation of potassium efflux by glutathione and glutathione adducts; when associated with A-416 and A-551. 1 Publication
Mutagenesisi520 – 5201E → G: Strongly reduced potassium efflux. 1 Publication
Mutagenesisi522 – 5221A → V: Strongly reduced potassium efflux. 1 Publication
Mutagenesisi526 – 5261G → V: Strongly reduced potassium efflux. 1 Publication
Mutagenesisi551 – 5511N → A: Increases constitutive potassium efflux and abolishes regulation of potassium efflux by glutathione and glutathione adducts; when associated with A-416 and A-516. 2 Publications
Mutagenesisi551 – 5511N → D: Increases constitutive potassium efflux; when associated with K-262. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 620620Glutathione-regulated potassium-efflux system protein KefCPRO_0000196606Add
BLAST

Proteomic databases

PaxDbiP03819.
PRIDEiP03819.

Interactioni

Subunit structurei

Homodimer. Interacts with the regulatory subunit KefF, forming a heterotetramer with 2:2 stoichiometry. Interaction with KefF is required for optimal activity. The active antiporter may be formed by the heterotetramer, or by an octamer.UniRule annotation3 Publications

GO - Molecular functioni

  • enzyme binding Source: EcoCyc

Protein-protein interaction databases

BioGridi4262200. 7 interactions.
DIPiDIP-10072N.
IntActiP03819. 2 interactions.
MINTiMINT-1257196.
STRINGi511145.b0047.

Structurei

Secondary structure

1
620
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi401 – 4055Combined sources
Helixi409 – 42012Combined sources
Beta strandi425 – 4295Combined sources
Helixi432 – 4409Combined sources
Beta strandi446 – 4483Combined sources
Helixi453 – 4586Combined sources
Turni459 – 4635Combined sources
Beta strandi465 – 4695Combined sources
Helixi474 – 48714Combined sources
Beta strandi492 – 4998Combined sources
Helixi500 – 5089Combined sources
Helixi519 – 53214Combined sources
Helixi537 – 56024Combined sources
Helixi565 – 57915Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3EYWX-ray2.40A/B401-620[»]
3L9WX-ray1.75A/B401-620[»]
3L9XX-ray2.10A/B401-620[»]
ProteinModelPortaliP03819.
SMRiP03819. Positions 6-311, 342-583.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03819.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini401 – 523123RCK N-terminalUniRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni259 – 2679Important for the regulation of potassium conductance
Regioni498 – 5003Glutathione binding

Domaini

The cytoplasmic RCK N-terminal domain regulates channel activity. It binds glutathione, resulting in inhibition of potassium efflux. In contrast, binding of the adducts formed between glutathione and electrophiles leads to activation of potassium efflux. Is expected to bind NADH, but X-ray crystallography shows bound AMP, and it would be difficult to accommodate NADH in this binding site (PubMed:21041667).1 Publication

Sequence similaritiesi

Belongs to the monovalent cation:proton antiporter 2 (CPA2) transporter (TC 2.A.37) family. KefC subfamily. [View classification]UniRule annotation
Contains 1 RCK N-terminal domain.UniRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG4105CKD. Bacteria.
COG0475. LUCA.
COG1226. LUCA.
HOGENOMiHOG000179076.
InParanoidiP03819.
KOiK11745.
OMAiRNRRHAY.
OrthoDBiEOG6XDGX2.
PhylomeDBiP03819.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
HAMAPiMF_01413. K_H_efflux_KefC.
InterProiIPR006153. Cation/H_exchanger.
IPR004771. K/H_exchanger.
IPR023941. K_H_efflux_KefC.
IPR006036. K_uptake_TrkA.
IPR016040. NAD(P)-bd_dom.
IPR003148. RCK_N.
[Graphical view]
PfamiPF00999. Na_H_Exchanger. 1 hit.
PF02254. TrkA_N. 1 hit.
[Graphical view]
PRINTSiPR00335. KUPTAKETRKA.
SUPFAMiSSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR00932. 2a37. 1 hit.
PROSITEiPS51201. RCK_N. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P03819-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDSHTLIQAL IYLGSAALIV PIAVRLGLGS VLGYLIAGCI IGPWGLRLVT
60 70 80 90 100
DAESILHFAE IGVVLMLFII GLELDPQRLW KLRAAVFGCG ALQMVICGGL
110 120 130 140 150
LGLFCMLLGL RWQVAELIGM TLALSSTAIA MQAMNERNLM VTQMGRSAFA
160 170 180 190 200
VLLFQDIAAI PLVAMIPLLA TSSASTTMGA FALSALKVAG ALVLVVLLGR
210 220 230 240 250
YVTRPALRFV ARSGLREVFS AVALFLVFGF GLLLEEVGLS MAMGAFLAGV
260 270 280 290 300
LLASSEYRHA LESDIEPFKG LLLGLFFIGV GMSIDFGTLL ENPLRIVILL
310 320 330 340 350
LGFLIIKIAM LWLIARPLQV PNKQRRWFAV LLGQGSEFAF VVFGAAQMAN
360 370 380 390 400
VLEPEWAKSL TLAVALSMAA TPILLVILNR LEQSSTEEAR EADEIDEEQP
410 420 430 440 450
RVIIAGFGRF GQITGRLLLS SGVKMVVLDH DPDHIETLRK FGMKVFYGDA
460 470 480 490 500
TRMDLLESAG AAKAEVLINA IDDPQTNLQL TEMVKEHFPH LQIIARARDV
510 520 530 540 550
DHYIRLRQAG VEKPERETFE GALKTGRLAL ESLGLGPYEA RERADVFRRF
560 570 580 590 600
NIQMVEEMAM VENDTKARAA VYKRTSAMLS EIITEDREHL SLIQRHGWQG
610 620
TEEGKHTGNM ADEPETKPSS
Length:620
Mass (Da):67,796
Last modified:November 1, 1991 - v2
Checksum:i9995B2E8E3C1DCE3
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X56742 Genomic DNA. Translation: CAA40066.1.
U00096 Genomic DNA. Translation: AAC73158.1.
AP009048 Genomic DNA. Translation: BAB96615.1.
J01609 Genomic DNA. No translation available.
PIRiS40568. QQECRD.
RefSeqiNP_414589.1. NC_000913.3.
WP_000377098.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC73158; AAC73158; b0047.
BAB96615; BAB96615; BAB96615.
GeneIDi944773.
KEGGiecj:JW0046.
eco:b0047.
PATRICi32115193. VBIEscCol129921_0048.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X56742 Genomic DNA. Translation: CAA40066.1.
U00096 Genomic DNA. Translation: AAC73158.1.
AP009048 Genomic DNA. Translation: BAB96615.1.
J01609 Genomic DNA. No translation available.
PIRiS40568. QQECRD.
RefSeqiNP_414589.1. NC_000913.3.
WP_000377098.1. NZ_LN832404.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3EYWX-ray2.40A/B401-620[»]
3L9WX-ray1.75A/B401-620[»]
3L9XX-ray2.10A/B401-620[»]
ProteinModelPortaliP03819.
SMRiP03819. Positions 6-311, 342-583.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4262200. 7 interactions.
DIPiDIP-10072N.
IntActiP03819. 2 interactions.
MINTiMINT-1257196.
STRINGi511145.b0047.

Protein family/group databases

TCDBi2.A.37.1.1. the monovalent cation:proton antiporter-2 (cpa2) family.

Proteomic databases

PaxDbiP03819.
PRIDEiP03819.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC73158; AAC73158; b0047.
BAB96615; BAB96615; BAB96615.
GeneIDi944773.
KEGGiecj:JW0046.
eco:b0047.
PATRICi32115193. VBIEscCol129921_0048.

Organism-specific databases

EchoBASEiEB0516.
EcoGeneiEG10521. kefC.

Phylogenomic databases

eggNOGiENOG4105CKD. Bacteria.
COG0475. LUCA.
COG1226. LUCA.
HOGENOMiHOG000179076.
InParanoidiP03819.
KOiK11745.
OMAiRNRRHAY.
OrthoDBiEOG6XDGX2.
PhylomeDBiP03819.

Enzyme and pathway databases

BioCyciEcoCyc:KEFC-MONOMER.
ECOL316407:JW0046-MONOMER.
MetaCyc:KEFC-MONOMER.

Miscellaneous databases

EvolutionaryTraceiP03819.
PROiP03819.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
HAMAPiMF_01413. K_H_efflux_KefC.
InterProiIPR006153. Cation/H_exchanger.
IPR004771. K/H_exchanger.
IPR023941. K_H_efflux_KefC.
IPR006036. K_uptake_TrkA.
IPR016040. NAD(P)-bd_dom.
IPR003148. RCK_N.
[Graphical view]
PfamiPF00999. Na_H_Exchanger. 1 hit.
PF02254. TrkA_N. 1 hit.
[Graphical view]
PRINTSiPR00335. KUPTAKETRKA.
SUPFAMiSSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR00932. 2a37. 1 hit.
PROSITEiPS51201. RCK_N. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The cloning and DNA sequence of the gene for the glutathione-regulated potassium-efflux system KefC of Escherichia coli."
    Munro A.W., Ritchie G.Y., Lamb A.J., Douglas R.M., Booth I.R.
    Mol. Microbiol. 5:607-616(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION.
    Strain: K12 / CS520.
  2. "Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region."
    Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K., Mizobuchi K., Nakata A.
    Nucleic Acids Res. 20:3305-3308(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  4. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
    Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
    Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  5. "Nucleotide sequence of the E coli gene coding for dihydrofolate reductase."
    Smith D.R., Calvo J.M.
    Nucleic Acids Res. 8:2255-2274(1980) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 500-620.
    Strain: K12.
  6. "The putative Na+/H+ antiporter (NapA) of Enterococcus hirae is homologous to the putative K+/H+ antiporter (KefC) of Escherichia coli."
    Reizer J., Reizer A., Saier M.H. Jr.
    FEMS Microbiol. Lett. 73:161-163(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: SIMILARITY TO NAPA.
  7. "Survival during exposure to the electrophilic reagent N-ethylmaleimide in Escherichia coli: role of KefB and KefC potassium channels."
    Ferguson G.P., Nikolaev Y., McLaggan D., Maclean M., Booth I.R.
    J. Bacteriol. 179:1007-1012(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION.
    Strain: K12.
  8. "Global topology analysis of the Escherichia coli inner membrane proteome."
    Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.
    Science 308:1321-1323(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY [LARGE SCALE ANALYSIS], SUBCELLULAR LOCATION.
    Strain: K12 / MG1655 / ATCC 47076.
  9. "Three two-component transporters with channel-like properties have monovalent cation/proton antiport activity."
    Fujisawa M., Ito M., Krulwich T.A.
    Proc. Natl. Acad. Sci. U.S.A. 104:13289-13294(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION, SUBUNIT.
  10. "KTN (RCK) domains regulate K+ channels and transporters by controlling the dimer-hinge conformation."
    Roosild T.P., Castronovo S., Miller S., Li C., Rasmussen T., Bartlett W., Gunasekera B., Choe S., Booth I.R.
    Structure 17:893-903(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 401-620 IN COMPLEX WITH KEFF AND AMP, SUBUNIT, INTERACTION WITH KEFF, MUTAGENESIS OF ASP-264; ARG-416; GLU-520; ALA-522; GLY-526 AND ASN-551, IDENTIFICATION BY MASS SPECTROMETRY.
  11. Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 401-620 IN COMPLEXES WITH KEFF; AMP AND GLUTATHIONE, FUNCTION, SUBUNIT, INTERACTION WITH KEFF, ENZYME REGULATION, DOMAIN, MUTAGENESIS OF GLN-412; ARG-416; PHE-441; ASP-499; ARG-516 AND ASN-551.

Entry informationi

Entry nameiKEFC_ECOLI
AccessioniPrimary (citable) accession number: P03819
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: November 1, 1991
Last modified: July 6, 2016
This is version 159 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.