CADC_ECOLI
ID CADC_ECOLI Reviewed; 512 AA.
AC P23890; Q2M6H0;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 25-MAY-2022, entry version 160.
DE RecName: Full=Transcriptional activator CadC {ECO:0000305};
DE AltName: Full=Membrane-integrated pH sensor CadC {ECO:0000303|PubMed:24056175};
GN Name=cadC; OrderedLocusNames=b4133, JW4094;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=JLS821;
RX PubMed=1370290; DOI=10.1128/jb.174.2.530-540.1992;
RA Watson N., Dunyak D.S., Rosey E.L., Slonczewski J.L., Olson E.R.;
RT "Identification of elements involved in transcriptional regulation of the
RT Escherichia coli cad operon by external pH.";
RL J. Bacteriol. 174:530-540(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=7610040; DOI=10.1093/nar/23.12.2105;
RA Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L., Blattner F.R.;
RT "Analysis of the Escherichia coli genome VI: DNA sequence of the region
RT from 92.8 through 100 minutes.";
RL Nucleic Acids Res. 23:2105-2119(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, AND MUTAGENESIS OF GLY-170;
RP ASN-263; GLN-266; GLY-284; ASP-471; THR-475; LEU-479 AND PRO-499.
RX PubMed=7830562; DOI=10.1111/j.1365-2958.1994.tb01262.x;
RA Dell C.L., Neely M.N., Olson E.R.;
RT "Altered pH and lysine signalling mutants of cadC, a gene encoding a
RT membrane-bound transcriptional activator of the Escherichia coli cadBA
RT operon.";
RL Mol. Microbiol. 14:7-16(1994).
RN [6]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=16491024; DOI=10.1159/000090346;
RA Kuper C., Jung K.;
RT "CadC-mediated activation of the cadBA promoter in Escherichia coli.";
RL J. Mol. Microbiol. Biotechnol. 10:26-39(2005).
RN [7]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH LYSP, DOMAIN, AND
RP MUTAGENESIS OF 159-PHE--PHE-165; 159-PHE-TRP-160; 162-TRP--PHE-165;
RP TRP-162; PHE-163; PHE-164; PHE-165 AND ARG-265.
RX PubMed=18086202; DOI=10.1111/j.1365-2958.2007.06070.x;
RA Tetsch L., Koller C., Haneburger I., Jung K.;
RT "The membrane-integrated transcriptional activator CadC of Escherichia coli
RT senses lysine indirectly via the interaction with the lysine permease
RT LysP.";
RL Mol. Microbiol. 67:570-583(2008).
RN [8]
RP FUNCTION, ACTIVITY REGULATION, DOMAIN, AND MUTAGENESIS OF ASP-198; ASP-200;
RP LYS-242; GLU-461; ARG-467; GLU-468; ASP-471; LEU-474; PHE-477 AND ASN-478.
RX PubMed=21216950; DOI=10.1074/jbc.m110.196923;
RA Haneburger I., Eichinger A., Skerra A., Jung K.;
RT "New insights into the signaling mechanism of the pH-responsive, membrane-
RT integrated transcriptional activator CadC of Escherichia coli.";
RL J. Biol. Chem. 286:10681-10689(2011).
RN [9]
RP ACTIVITY REGULATION, DISULFIDE BOND, AND MUTAGENESIS OF CYS-172; CYS-208
RP AND CYS-272.
RX PubMed=21486484; DOI=10.1186/1471-2180-11-74;
RA Tetsch L., Koller C., Doenhoefer A., Jung K.;
RT "Detection and function of an intramolecular disulfide bond in the pH-
RT responsive CadC of Escherichia coli.";
RL BMC Microbiol. 11:74-74(2011).
RN [10]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-225; THR-229; GLU-447; TYR-453;
RP LEU-474; THR-475; PHE-477 AND ASN-478.
RX PubMed=22999955; DOI=10.1016/j.jmb.2012.08.023;
RA Haneburger I., Fritz G., Jurkschat N., Tetsch L., Eichinger A., Skerra A.,
RA Gerland U., Jung K.;
RT "Deactivation of the E. coli pH stress sensor CadC by cadaverine.";
RL J. Mol. Biol. 424:15-27(2012).
RN [11]
RP INDUCTION, AND MUTAGENESIS OF PRO-121 AND 120-PRO--PRO-124.
RC STRAIN=K12 / BW25113, and K12 / MG1655 / ATCC 47076;
RX PubMed=23239623; DOI=10.1126/science.1228985;
RA Ude S., Lassak J., Starosta A.L., Kraxenberger T., Wilson D.N., Jung K.;
RT "Translation elongation factor EF-P alleviates ribosome stalling at
RT polyproline stretches.";
RL Science 339:82-85(2013).
RN [12]
RP ACTIVITY REGULATION, INTERACTION WITH LYSP, DOMAIN, AND MUTAGENESIS OF
RP PHE-165; ARG-265 AND ARG-268.
RX PubMed=24056175; DOI=10.1016/j.jmb.2013.09.017;
RA Rauschmeier M., Schueppel V., Tetsch L., Jung K.;
RT "New insights into the interplay between the lysine transporter LysP and
RT the pH sensor CadC in Escherichia coli.";
RL J. Mol. Biol. 426:215-229(2014).
RN [13]
RP SUBUNIT, SUBCELLULAR LOCATION, AND DOMAIN.
RC STRAIN=K12;
RX PubMed=24946151; DOI=10.1016/j.jmb.2014.06.006;
RA Lindner E., White S.H.;
RT "Topology, dimerization, and stability of the single-span membrane protein
RT CadC.";
RL J. Mol. Biol. 426:2942-2957(2014).
RN [14] {ECO:0007744|PDB:3LY7, ECO:0007744|PDB:3LY8, ECO:0007744|PDB:3LY9, ECO:0007744|PDB:3LYA}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 188-512 OF WILD-TYPE AND MUTANTS
RP GLU-471 AND ASN-471, SUBUNIT, DOMAIN, AND DISULFIDE BOND.
RX PubMed=21308846; DOI=10.1002/pro.594;
RA Eichinger A., Haneburger I., Koller C., Jung K., Skerra A.;
RT "Crystal structure of the sensory domain of Escherichia coli CadC, a member
RT of the ToxR-like protein family.";
RL Protein Sci. 20:656-669(2011).
RN [15] {ECO:0007744|PDB:5JU7}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 2-107, FUNCTION, DNA-BINDING, AND
RP MUTAGENESIS OF GLU-30; ARG-32; ARG-50; ARG-60; VAL-63; THR-64; HIS-66;
RP THR-69; GLN-70; SER-73; ARG-76; LYS-95 AND ARG-96.
RX PubMed=28432336; DOI=10.1038/s41598-017-01031-9;
RA Schlundt A., Buchner S., Janowski R., Heydenreich T., Heermann R.,
RA Lassak J., Geerlof A., Stehle R., Niessing D., Jung K., Sattler M.;
RT "Structure-function analysis of the DNA-binding domain of a transmembrane
RT transcriptional activator.";
RL Sci. Rep. 7:1051-1051(2017).
CC -!- FUNCTION: Regulates the lysine- and pH-dependent expression of the
CC lysine decarboxylase CadA and the cadaverine-lysine antiporter CadB
CC (PubMed:1370290, PubMed:16491024, PubMed:18086202, PubMed:21216950). At
CC low external pH, and in the presence of external lysine, CadC activates
CC transcription of the cadBA operon by binding directly to two sites,
CC Cad1 and Cad2, within the cadBA promoter region (Pcad)
CC (PubMed:16491024, PubMed:28432336). Preferentially binds to AT-rich
CC regions within the Cad1 promoter (PubMed:28432336).
CC {ECO:0000269|PubMed:1370290, ECO:0000269|PubMed:16491024,
CC ECO:0000269|PubMed:18086202, ECO:0000269|PubMed:21216950,
CC ECO:0000269|PubMed:28432336}.
CC -!- ACTIVITY REGULATION: Activation of CadC requires two stimuli, lysine
CC and low pH (PubMed:18086202, PubMed:21216950, PubMed:21486484,
CC PubMed:24056175). CadC shows an extremely low affinity for lysine, and
CC it senses the extracellular lysine not directly but indirectly via
CC interaction with the lysine permease LysP (PubMed:18086202). At a low
CC external lysine concentration, CadC is inactivated by an interaction
CC with LysP. When lysine is abundantly available, the interaction between
CC LysP and CadC is released, and CadC becomes susceptible to activation
CC by low pH (PubMed:18086202, PubMed:24056175). Acidification of the
CC external milieu is sensed by protonation of a patch of acidic amino
CC acids within the periplasmic domain and associated to conformational
CC and/or oligomerization effects (PubMed:21216950). The pH-dependent
CC regulation may be due to the presence/absence of a disulfide bond
CC within the periplasmic domain (PubMed:21486484). At pH 7.6, a disulfide
CC bond is found in the inactive state of CadC. At pH 5.8, disulfide bond
CC formation is prevented, which transforms CadC into a semi-active state
CC with respect to both the pH and the lysine stimuli (PubMed:21486484).
CC Activity is also feedback inhibited by cadaverine (PubMed:22999955).
CC Cadaverine binds first to the central cavity, which putatively triggers
CC intramolecular rearrangements to expose the binding sites for
CC cadaverine at the dimer interface, which inactivates CadC and
CC consequently shuts off transcription of the cadBA operon
CC (PubMed:22999955). {ECO:0000269|PubMed:18086202,
CC ECO:0000269|PubMed:21216950, ECO:0000269|PubMed:21486484,
CC ECO:0000269|PubMed:22999955, ECO:0000269|PubMed:24056175}.
CC -!- SUBUNIT: Homodimer (PubMed:21308846, PubMed:24946151). Dimerization of
CC the periplasmic domain is required for activation of the cadBA operon
CC (PubMed:24946151). Interacts strongly with the lysine permease LysP in
CC the absence of lysine or at low lysine concentrations (PubMed:18086202,
CC PubMed:24056175). Interaction is markedly attenuated under increasing
CC lysine levels (PubMed:24056175). Concomitant pH-dependent protonation
CC of periplasmic amino acids in both proteins dissolves their
CC electrostatic connections resulting in further destabilization of the
CC CadC/LysP interaction (PubMed:24056175). {ECO:0000269|PubMed:18086202,
CC ECO:0000269|PubMed:21308846, ECO:0000269|PubMed:24056175,
CC ECO:0000269|PubMed:24946151}.
CC -!- INTERACTION:
CC P23890; P25737: lysP; NbExp=2; IntAct=EBI-6401662, EBI-6401655;
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:24946151,
CC ECO:0000269|PubMed:7830562}; Single-pass membrane protein
CC {ECO:0000269|PubMed:24946151}. Note=Membrane insertion requires the
CC SecA translocase. {ECO:0000269|PubMed:24946151}.
CC -!- INDUCTION: Translation requires the translation elongation factor P
CC (EF-P). This requirement is reduced as the number of consecutive Pro
CC residues in the protein is decreased. {ECO:0000269|PubMed:23239623}.
CC -!- DOMAIN: Contains a cytoplasmic DNA-binding N-terminal domain, a
CC transmembrane domain and a periplasmic C-terminal domain
CC (PubMed:7830562, PubMed:24946151). A cluster of aromatic amino acids
CC within the transmembrane domain is important for lysine-dependent
CC regulation of CadC (PubMed:18086202). The transmembrane domain of CadC
CC is important for the interaction with LysP, but the periplasmic domain
CC of CadC is also important in facilitating correct positioning of the
CC two proteins (PubMed:24056175). A cluster of negatively charged amino
CC acids (Asp-198, Asp-200, Glu-461, Glu-468 and Asp-471) forms a
CC negatively charged patch on the surface of the periplasmic domain and
CC is crucial for pH detection (PubMed:21216950). Dimerization requires
CC the periplasmic domain, but not the transmembrane domain
CC (PubMed:24946151). Conformational changes at the dimer interface may
CC functionally influence the transcriptional activity (PubMed:21308846).
CC {ECO:0000269|PubMed:18086202, ECO:0000269|PubMed:21216950,
CC ECO:0000269|PubMed:21308846, ECO:0000269|PubMed:24056175,
CC ECO:0000269|PubMed:24946151, ECO:0000269|PubMed:7830562}.
CC -!- PTM: Contains a functionally important disulfide bond, which may
CC provide structural support for the pH-dependent activation via a switch
CC of the sensor between the inactive and active state.
CC {ECO:0000269|PubMed:21486484}.
CC -!- DISRUPTION PHENOTYPE: Loss of Pcad activity.
CC {ECO:0000269|PubMed:1370290}.
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DR EMBL; M67452; AAA23531.1; -; Genomic_DNA.
DR EMBL; U14003; AAA97033.1; -; Genomic_DNA.
DR EMBL; U00096; AAC77094.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE78136.1; -; Genomic_DNA.
DR PIR; C41968; C41968.
DR RefSeq; NP_418557.1; NC_000913.3.
DR RefSeq; WP_001187173.1; NZ_SSZK01000018.1.
DR PDB; 3LY7; X-ray; 1.80 A; A=188-512.
DR PDB; 3LY8; X-ray; 1.90 A; A=188-512.
DR PDB; 3LY9; X-ray; 2.20 A; A=188-512.
DR PDB; 3LYA; X-ray; 2.30 A; A=188-512.
DR PDB; 5JU7; X-ray; 2.05 A; A=2-107.
DR PDBsum; 3LY7; -.
DR PDBsum; 3LY8; -.
DR PDBsum; 3LY9; -.
DR PDBsum; 3LYA; -.
DR PDBsum; 5JU7; -.
DR AlphaFoldDB; P23890; -.
DR SMR; P23890; -.
DR BioGRID; 4260781; 7.
DR BioGRID; 852945; 1.
DR DIP; DIP-9239N; -.
DR IntAct; P23890; 1.
DR STRING; 511145.b4133; -.
DR PaxDb; P23890; -.
DR PRIDE; P23890; -.
DR DNASU; 948653; -.
DR EnsemblBacteria; AAC77094; AAC77094; b4133.
DR EnsemblBacteria; BAE78136; BAE78136; BAE78136.
DR GeneID; 948653; -.
DR KEGG; ecj:JW4094; -.
DR KEGG; eco:b4133; -.
DR PATRIC; fig|1411691.4.peg.2566; -.
DR EchoBASE; EB0131; -.
DR eggNOG; COG3710; Bacteria.
DR HOGENOM; CLU_040424_0_0_6; -.
DR OMA; VIWCTEE; -.
DR PhylomeDB; P23890; -.
DR BioCyc; EcoCyc:PD00436; -.
DR EvolutionaryTrace; P23890; -.
DR PRO; PR:P23890; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:EcoCyc.
DR GO; GO:0032993; C:protein-DNA complex; IBA:GO_Central.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; IBA:GO_Central.
DR GO; GO:0000156; F:phosphorelay response regulator activity; IBA:GO_Central.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:EcoCyc.
DR CDD; cd00383; trans_reg_C; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR040970; CadC_C1.
DR InterPro; IPR001867; OmpR/PhoB-type_DNA-bd.
DR InterPro; IPR016032; Sig_transdc_resp-reg_C-effctor.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR039420; WalR-like.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR PANTHER; PTHR48111; PTHR48111; 1.
DR Pfam; PF18500; CadC_C1; 1.
DR Pfam; PF00486; Trans_reg_C; 1.
DR SMART; SM00862; Trans_reg_C; 1.
DR SUPFAM; SSF46894; SSF46894; 1.
DR PROSITE; PS51755; OMPR_PHOB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cell inner membrane; Cell membrane;
KW Disulfide bond; DNA-binding; Membrane; Reference proteome; Transcription;
KW Transcription regulation; Transmembrane; Transmembrane helix.
FT CHAIN 1..512
FT /note="Transcriptional activator CadC"
FT /id="PRO_0000081345"
FT TOPO_DOM 1..154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24946151,
FT ECO:0000305|PubMed:7830562"
FT TRANSMEM 155..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 181..512
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:24946151,
FT ECO:0000305|PubMed:7830562"
FT DNA_BIND 3..102
FT /note="OmpR/PhoB-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01091"
FT SITE 265
FT /note="Essential for the stimulus-dependent interaction
FT with LysP"
FT /evidence="ECO:0000269|PubMed:24056175"
FT SITE 268
FT /note="Essential for the stimulus-dependent interaction
FT with LysP"
FT /evidence="ECO:0000269|PubMed:24056175"
FT DISULFID 208..272
FT /evidence="ECO:0000269|PubMed:21308846,
FT ECO:0000269|PubMed:21486484, ECO:0007744|PDB:3LY7,
FT ECO:0007744|PDB:3LY8, ECO:0007744|PDB:3LY9,
FT ECO:0007744|PDB:3LYA"
FT MUTAGEN 30
FT /note="E->R: Enhances the DNA-binding affinity and induces
FT constitutive cadBA promoter activation independent of pH
FT and lysine."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 32
FT /note="R->A: Strongly affects DNA-binding. Abolishes
FT activation of the cadBA promoter under all tested
FT conditions."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 50
FT /note="R->A: Strongly affects DNA-binding. Abolishes
FT activation of the cadBA promoter under all tested
FT conditions."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 60
FT /note="R->A: Strongly affects DNA-binding. Abolishes
FT activation of the cadBA promoter under all tested
FT conditions."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 63
FT /note="V->A: Strongly affects DNA-binding. Abolishes
FT activation of the cadBA promoter under all tested
FT conditions."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 64
FT /note="T->A: Strongly affects DNA-binding. Abolishes
FT activation of the cadBA promoter under all tested
FT conditions."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 66
FT /note="H->A: Strongly affects DNA-binding. Abolishes
FT activation of the cadBA promoter under all tested
FT conditions."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 69
FT /note="T->A: Strongly affects DNA-binding. Abolishes
FT activation of the cadBA promoter under all tested
FT conditions."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 70
FT /note="Q->A: Strongly affects DNA-binding. Abolishes
FT activation of the cadBA promoter under all tested
FT conditions."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 73
FT /note="S->A: Strongly affects DNA-binding. Abolishes
FT activation of the cadBA promoter under all tested
FT conditions."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 76
FT /note="R->A: Strongly affects DNA-binding. Abolishes
FT activation of the cadBA promoter under all tested
FT conditions."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 95
FT /note="K->A: Strongly affects DNA-binding. Abolishes
FT activation of the cadBA promoter under all tested
FT conditions."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 96
FT /note="R->A: Strongly affects DNA-binding. Abolishes
FT activation of the cadBA promoter under all tested
FT conditions."
FT /evidence="ECO:0000269|PubMed:28432336"
FT MUTAGEN 120..124
FT /note="PPPIP->AAAIS: Significantly reduced dependence on
FT EF-P for translation, increased levels of protein in an
FT efp-strain."
FT /evidence="ECO:0000269|PubMed:23239623"
FT MUTAGEN 121
FT /note="P->A: Reduced dependence on EF-P for translation,
FT increased levels of protein in an efp- strain."
FT /evidence="ECO:0000269|PubMed:23239623"
FT MUTAGEN 159..165
FT /note="FWVWFFF->LVVALVA: Expression of cadBA becomes
FT lysine-independent. Strong decrease in regulation by LysP."
FT /evidence="ECO:0000269|PubMed:18086202"
FT MUTAGEN 159..165
FT /note="Missing: Expression of cadBA becomes lysine-
FT independent. Lack of regulation by LysP."
FT /evidence="ECO:0000269|PubMed:18086202"
FT MUTAGEN 159..160
FT /note="FW->LV: Expression of cadBA is lysine-dependent."
FT /evidence="ECO:0000269|PubMed:18086202"
FT MUTAGEN 162..165
FT /note="WFFF->ALVA: Expression of cadBA becomes lysine-
FT independent. Strong decrease in regulation by LysP."
FT /evidence="ECO:0000269|PubMed:18086202"
FT MUTAGEN 162
FT /note="W->A: Expression of cadBA becomes lysine-
FT independent, but to a minor degree. Small decrease in
FT regulation by LysP."
FT /evidence="ECO:0000269|PubMed:18086202"
FT MUTAGEN 163
FT /note="F->L: Expression of cadBA is lysine-dependent."
FT /evidence="ECO:0000269|PubMed:18086202"
FT MUTAGEN 164
FT /note="F->V: Expression of cadBA is lysine-dependent."
FT /evidence="ECO:0000269|PubMed:18086202"
FT MUTAGEN 165
FT /note="F->A: Expression of cadBA becomes lysine-
FT independent. Strong decrease in regulation by LysP.
FT Prevents interaction with LysP."
FT /evidence="ECO:0000269|PubMed:18086202,
FT ECO:0000269|PubMed:24056175"
FT MUTAGEN 170
FT /note="G->D: Confers both pH- and lysine-independent cadBA
FT expression."
FT /evidence="ECO:0000269|PubMed:7830562"
FT MUTAGEN 172
FT /note="C->A: Retains wild-type activity, induces expression
FT of the cadAB operon only at low pH in the presence of
FT lysine."
FT /evidence="ECO:0000269|PubMed:21486484"
FT MUTAGEN 198
FT /note="D->A,E,N: Abolishes response to the external low pH
FT signal."
FT /evidence="ECO:0000269|PubMed:21216950"
FT MUTAGEN 200
FT /note="D->A,E,N: Abolishes response to the external low pH
FT signal."
FT /evidence="ECO:0000269|PubMed:21216950"
FT MUTAGEN 208
FT /note="C->A: Induces cadBA expression at pH 5.8 regardless
FT of the presence of lysine, and at pH 7.6 when lysine is
FT present. Weakens interaction with LysP."
FT /evidence="ECO:0000269|PubMed:21486484"
FT MUTAGEN 225
FT /note="D->W: Decreases inhibition by cadaverine."
FT /evidence="ECO:0000269|PubMed:22999955"
FT MUTAGEN 229
FT /note="T->A: Decreases inhibition by cadaverine."
FT /evidence="ECO:0000269|PubMed:22999955"
FT MUTAGEN 242
FT /note="K->R: Confers pH-independent cadBA expression."
FT /evidence="ECO:0000269|PubMed:21216950"
FT MUTAGEN 263
FT /note="N->K: Confers both pH- and lysine-independent cadBA
FT expression."
FT /evidence="ECO:0000269|PubMed:7830562"
FT MUTAGEN 265
FT /note="R->A: Displays lysine-independent, but pH-dependent
FT induction of cadBA; when associated with A-268."
FT /evidence="ECO:0000269|PubMed:24056175"
FT MUTAGEN 265
FT /note="R->C: Is inserted into the membrane properly and can
FT induce cadBA expression in the presence or absence of
FT lysine."
FT /evidence="ECO:0000269|PubMed:18086202"
FT MUTAGEN 265
FT /note="R->K,S,Q: Is inserted into the membrane properly and
FT can induce cadBA expression in the presence of lysine but
FT not in absence of lysine."
FT /evidence="ECO:0000269|PubMed:18086202"
FT MUTAGEN 266
FT /note="Q->P: Confers both pH- and lysine-independent cadBA
FT expression."
FT /evidence="ECO:0000269|PubMed:7830562"
FT MUTAGEN 268
FT /note="R->A: Displays lysine-independent, but pH-dependent
FT induction of cadBA; when associated with A-265."
FT /evidence="ECO:0000269|PubMed:24056175"
FT MUTAGEN 272
FT /note="C->A: Induces cadBA expression at pH 5.8 regardless
FT of the presence of lysine, and at pH 7.6 when lysine is
FT present. Weakens interaction with LysP."
FT /evidence="ECO:0000269|PubMed:21486484"
FT MUTAGEN 284
FT /note="G->D: Confers pH-independent cadBA expression, but
FT does not affect the requirement for the lysine signal."
FT /evidence="ECO:0000269|PubMed:7830562"
FT MUTAGEN 447
FT /note="E->Q: Decreases inhibition by cadaverine."
FT /evidence="ECO:0000269|PubMed:22999955"
FT MUTAGEN 453
FT /note="Y->A,I: Decreases inhibition by cadaverine."
FT /evidence="ECO:0000269|PubMed:22999955"
FT MUTAGEN 461
FT /note="E->A,D,Q,R: Abolishes response to the external low
FT pH signal."
FT /evidence="ECO:0000269|PubMed:21216950"
FT MUTAGEN 467
FT /note="R->A,E,K,Q: Abolishes response to the external low
FT pH signal."
FT /evidence="ECO:0000269|PubMed:21216950"
FT MUTAGEN 468
FT /note="E->A,Q,R: Abolishes response to the external low pH
FT signal."
FT /evidence="ECO:0000269|PubMed:21216950"
FT MUTAGEN 468
FT /note="E->D: Can still respond to pH, albeit with lower
FT activity."
FT /evidence="ECO:0000269|PubMed:21216950"
FT MUTAGEN 471
FT /note="D->A,N: Confers pH-independent cadBA expression."
FT /evidence="ECO:0000269|PubMed:21216950"
FT MUTAGEN 471
FT /note="D->E,R: Abolishes response to the external low pH
FT signal."
FT /evidence="ECO:0000269|PubMed:21216950"
FT MUTAGEN 471
FT /note="D->G: Confers pH-independent cadBA expression, but
FT does not affect the requirement for the lysine signal."
FT /evidence="ECO:0000269|PubMed:7830562"
FT MUTAGEN 474
FT /note="L->A: Confers pH-independent cadBA expression.
FT Decreases inhibition by cadaverine."
FT /evidence="ECO:0000269|PubMed:21216950,
FT ECO:0000269|PubMed:22999955"
FT MUTAGEN 475
FT /note="T->A: Confers pH-independent cadBA expression, but
FT does not affect the requirement for the lysine signal.
FT Decreases inhibition by cadaverine."
FT /evidence="ECO:0000269|PubMed:22999955,
FT ECO:0000269|PubMed:7830562"
FT MUTAGEN 475
FT /note="T->S: Decreases inhibition by cadaverine."
FT /evidence="ECO:0000269|PubMed:22999955"
FT MUTAGEN 477
FT /note="F->A: Does not alter pH sensing."
FT /evidence="ECO:0000269|PubMed:21216950"
FT MUTAGEN 477
FT /note="F->I: Is almost pH-insensitive. Decreases inhibition
FT by cadaverine."
FT /evidence="ECO:0000269|PubMed:21216950,
FT ECO:0000269|PubMed:22999955"
FT MUTAGEN 478
FT /note="N->A: Confers pH-independent cadBA expression.
FT Decreases inhibition by cadaverine."
FT /evidence="ECO:0000269|PubMed:21216950,
FT ECO:0000269|PubMed:22999955"
FT MUTAGEN 479
FT /note="L->S: Confers pH-independent cadBA expression, but
FT does not affect the requirement for the lysine signal."
FT /evidence="ECO:0000269|PubMed:7830562"
FT MUTAGEN 499
FT /note="P->L: Confers pH-independent cadBA expression, but
FT does not affect the requirement for the lysine signal."
FT /evidence="ECO:0000269|PubMed:7830562"
FT STRAND 6..8
FT /evidence="ECO:0007829|PDB:5JU7"
FT STRAND 11..14
FT /evidence="ECO:0007829|PDB:5JU7"
FT HELIX 15..17
FT /evidence="ECO:0007829|PDB:5JU7"
FT STRAND 19..21
FT /evidence="ECO:0007829|PDB:5JU7"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:5JU7"
FT HELIX 31..42
FT /evidence="ECO:0007829|PDB:5JU7"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:5JU7"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:5JU7"
FT HELIX 50..57
FT /evidence="ECO:0007829|PDB:5JU7"
FT HELIX 65..80
FT /evidence="ECO:0007829|PDB:5JU7"
FT STRAND 89..93
FT /evidence="ECO:0007829|PDB:5JU7"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:5JU7"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:5JU7"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:5JU7"
FT STRAND 195..204
FT /evidence="ECO:0007829|PDB:3LY7"
FT STRAND 206..211
FT /evidence="ECO:0007829|PDB:3LY8"
FT HELIX 216..234
FT /evidence="ECO:0007829|PDB:3LY7"
FT STRAND 238..241
FT /evidence="ECO:0007829|PDB:3LY7"
FT STRAND 253..262
FT /evidence="ECO:0007829|PDB:3LY7"
FT STRAND 273..280
FT /evidence="ECO:0007829|PDB:3LY7"
FT TURN 281..283
FT /evidence="ECO:0007829|PDB:3LY7"
FT STRAND 286..292
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 299..313
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 320..329
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 334..336
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 337..349
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 352..368
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 373..389
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 394..408
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 417..430
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 433..446
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 450..462
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 466..479
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 483..491
FT /evidence="ECO:0007829|PDB:3LY7"
FT STRAND 492..494
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 498..501
FT /evidence="ECO:0007829|PDB:3LY7"
FT HELIX 503..510
FT /evidence="ECO:0007829|PDB:3LY7"
SQ SEQUENCE 512 AA; 57813 MW; AA19F5E1D293ACCF CRC64;
MQQPVVRVGE WLVTPSINQI SRNGRQLTLE PRLIDLLVFF AQHSGEVLSR DELIDNVWKR
SIVTNHVVTQ SISELRKSLK DNDEDSPVYI ATVPKRGYKL MVPVIWYSEE EGEEIMLSSP
PPIPEAVPAT DSPSHSLNIQ NTATPPEQSP VKSKRFTTFW VWFFFLLSLG ICVALVAFSS
LDTRLPMSKS RILLNPRDID INMVNKSCNS WSSPYQLSYA IGVGDLVATS LNTFSTFMVH
DKINYNIDEP SSSGKTLSIA FVNQRQYRAQ QCFMSIKLVD NADGSTMLDK RYVITNGNQL
AIQNDLLESL SKALNQPWPQ RMQETLQKIL PHRGALLTNF YQAHDYLLHG DDKSLNRASE
LLGEIVQSSP EFTYARAEKA LVDIVRHSQH PLDEKQLAAL NTEIDNIVTL PELNNLSIIY
QIKAVSALVK GKTDESYQAI NTGIDLEMSW LNYVLLGKVY EMKGMNREAA DAYLTAFNLR
PGANTLYWIE NGIFQTSVPY VVPYLDKFLA SE
