CADC_STAAU
ID CADC_STAAU Reviewed; 122 AA.
AC P20047;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Cadmium resistance transcriptional regulatory protein CadC;
DE AltName: Full=Cadmium efflux system accessory protein;
GN Name=cadC;
OS Staphylococcus aureus.
OG Plasmid pI258.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2524829; DOI=10.1073/pnas.86.10.3544;
RA Nucifora G., Chu L., Misra T.K., Silver S.;
RT "Cadmium resistance from Staphylococcus aureus plasmid pI258 cadA gene
RT results from a cadmium-efflux ATPase.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:3544-3548(1989).
RN [2]
RP IDENTIFICATION.
RX PubMed=1938959; DOI=10.1128/jb.173.23.7636-7642.1991;
RA Yoon K.P., Silver S.;
RT "A second gene in the Staphylococcus aureus cadA cadmium resistance
RT determinant of plasmid pI258.";
RL J. Bacteriol. 173:7636-7642(1991).
RN [3]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=7543476; DOI=10.1128/jb.177.15.4437-4441.1995;
RA Endo G., Silver S.;
RT "CadC, the transcriptional regulatory protein of the cadmium resistance
RT system of Staphylococcus aureus plasmid pI258.";
RL J. Bacteriol. 177:4437-4441(1995).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF CYS-7; CYS-11; CYS-58 AND CYS-60.
RX PubMed=11278706; DOI=10.1074/jbc.m010595200;
RA Sun Y., Wong M.D., Rosen B.P.;
RT "Role of cysteinyl residues in sensing Pb(II), Cd(II), and Zn(II) by the
RT plasmid pI258 CadC repressor.";
RL J. Biol. Chem. 276:14955-14960(2001).
RN [5]
RP FUNCTION, SUBUNIT, MUTAGENESIS OF HIS-103, AND METAL BINDING SITES.
RX PubMed=12176999; DOI=10.1074/jbc.m206536200;
RA Wong M.D., Lin Y.-F., Rosen B.P.;
RT "The soft metal ion binding sites in the Staphylococcus aureus pI258 CadC
RT Cd(II)/Pb(II)/Zn(II)-responsive repressor are formed between subunits of
RT the homodimer.";
RL J. Biol. Chem. 277:40930-40936(2002).
RN [6]
RP FUNCTION, AND SUBUNIT.
RX PubMed=11941514; DOI=10.1007/s00775-001-0336-9;
RA Busenlehner L.S., Apuy J.L., Giedroc D.P.;
RT "Characterization of a metalloregulatory bismuth(III) site in
RT Staphylococcus aureus pI258 CadC repressor.";
RL J. Biol. Inorg. Chem. 7:551-559(2002).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH ZINC IONS, AND
RP SUBUNIT.
RX PubMed=15937183; DOI=10.1128/jb.187.12.4214-4221.2005;
RA Ye J., Kandegedara A., Martin P., Rosen B.P.;
RT "Crystal structure of the Staphylococcus aureus pI258 CadC
RT Cd(II)/Pb(II)/Zn(II)-responsive repressor.";
RL J. Bacteriol. 187:4214-4221(2005).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH METAL IONS, FUNCTION,
RP CHARACTERIZATION OF METAL BINDING SITES, SUBUNIT, AND MUTAGENESIS OF CYS-7;
RP CYS-11; CYS-58; CYS-60; ASP-101 AND HIS-103.
RX PubMed=19286656; DOI=10.1074/jbc.m809179200;
RA Kandegedara A., Thiyagarajan S., Kondapalli K.C., Stemmler T.L.,
RA Rosen B.P.;
RT "Role of bound Zn(II) in the CadC Cd(II)/Pb(II)/Zn(II)-responsive
RT repressor.";
RL J. Biol. Chem. 284:14958-14965(2009).
CC -!- FUNCTION: Metal-binding repressor for the cad operon. Involved in
CC resistance to heavy metals, such as cadmium, bismuth, zinc or lead.
CC Binds 2 metal ions per subunit. Metal binding to the N-terminal
CC regulatory site causes the repressor to dissociate from the DNA.
CC {ECO:0000269|PubMed:11278706, ECO:0000269|PubMed:11941514,
CC ECO:0000269|PubMed:12176999, ECO:0000269|PubMed:19286656,
CC ECO:0000269|PubMed:7543476}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11941514,
CC ECO:0000269|PubMed:12176999, ECO:0000269|PubMed:15937183,
CC ECO:0000269|PubMed:19286656}.
CC -!- MISCELLANEOUS: The N-terminal, regulatory metal binding site 1 has
CC higher affinity for cadmium than for zinc. The second metal binding
CC site has higher affinity for zinc and has no regulatory function.
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DR EMBL; J04551; AAB59153.1; -; Genomic_DNA.
DR PIR; B32561; B32561.
DR RefSeq; WP_000726007.1; NZ_WWCF01000009.1.
DR RefSeq; YP_006937601.1; NC_013319.1.
DR RefSeq; YP_006937788.1; NC_013323.1.
DR RefSeq; YP_006938262.1; NC_013337.1.
DR RefSeq; YP_006938636.1; NC_013347.1.
DR RefSeq; YP_006938769.1; NC_013352.1.
DR PDB; 1U2W; X-ray; 1.90 A; A/B/C/D=1-122.
DR PDB; 3F72; X-ray; 2.31 A; A/B/C/D/E/F=1-122.
DR PDBsum; 1U2W; -.
DR PDBsum; 3F72; -.
DR AlphaFoldDB; P20047; -.
DR SMR; P20047; -.
DR EvolutionaryTrace; P20047; -.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046686; P:response to cadmium ion; IEA:UniProtKB-KW.
DR CDD; cd00090; HTH_ARSR; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR011991; ArsR-like_HTH.
DR InterPro; IPR018334; ArsR_HTH.
DR InterPro; IPR001845; HTH_ArsR_DNA-bd_dom.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF01022; HTH_5; 1.
DR PRINTS; PR00778; HTHARSR.
DR SMART; SM00418; HTH_ARSR; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00846; HTH_ARSR_1; 1.
DR PROSITE; PS50987; HTH_ARSR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cadmium; Cadmium resistance; DNA-binding; Metal-binding;
KW Plasmid; Transcription; Transcription regulation; Zinc.
FT CHAIN 1..122
FT /note="Cadmium resistance transcriptional regulatory
FT protein CadC"
FT /id="PRO_0000160620"
FT DOMAIN 24..119
FT /note="HTH arsR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00340"
FT DNA_BIND 59..78
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00340"
FT BINDING 7
FT /ligand="Cd(2+)"
FT /ligand_id="ChEBI:CHEBI:48775"
FT /ligand_note="ligand shared between dimeric partners"
FT BINDING 11
FT /ligand="Cd(2+)"
FT /ligand_id="ChEBI:CHEBI:48775"
FT /ligand_note="ligand shared between dimeric partners"
FT BINDING 58
FT /ligand="Cd(2+)"
FT /ligand_id="ChEBI:CHEBI:48775"
FT /ligand_note="ligand shared between dimeric partners"
FT BINDING 60
FT /ligand="Cd(2+)"
FT /ligand_id="ChEBI:CHEBI:48775"
FT /ligand_note="ligand shared between dimeric partners"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared between dimeric partners"
FT BINDING 103
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared between dimeric partners"
FT BINDING 114
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared between dimeric partners"
FT BINDING 117
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared between dimeric partners"
FT MUTAGEN 7
FT /note="C->S: Abolishes dissociation from DNA; when
FT associated with G-11; S-58 and S-60."
FT /evidence="ECO:0000269|PubMed:11278706,
FT ECO:0000269|PubMed:19286656"
FT MUTAGEN 11
FT /note="C->G: No effect. Abolishes dissociation from DNA;
FT when associated with S-7; S-58 and S-60."
FT /evidence="ECO:0000269|PubMed:11278706,
FT ECO:0000269|PubMed:19286656"
FT MUTAGEN 58
FT /note="C->S: Abolishes dissociation from DNA; when
FT associated with S-7; G-11 and S-60."
FT /evidence="ECO:0000269|PubMed:11278706,
FT ECO:0000269|PubMed:19286656"
FT MUTAGEN 60
FT /note="C->S: Abolishes dissociation from DNA; when
FT associated with S-7; G-11 and S-58."
FT /evidence="ECO:0000269|PubMed:11278706,
FT ECO:0000269|PubMed:19286656"
FT MUTAGEN 101
FT /note="D->G: No effect on repressor activity; when
FT associated with A-103."
FT /evidence="ECO:0000269|PubMed:19286656"
FT MUTAGEN 103
FT /note="H->A: No effect on repressor activity; when
FT associated with G-101."
FT /evidence="ECO:0000269|PubMed:12176999,
FT ECO:0000269|PubMed:19286656"
FT STRAND 11..13
FT /evidence="ECO:0007829|PDB:3F72"
FT HELIX 14..25
FT /evidence="ECO:0007829|PDB:1U2W"
FT TURN 26..28
FT /evidence="ECO:0007829|PDB:1U2W"
FT HELIX 29..40
FT /evidence="ECO:0007829|PDB:1U2W"
FT HELIX 42..53
FT /evidence="ECO:0007829|PDB:1U2W"
FT HELIX 59..66
FT /evidence="ECO:0007829|PDB:1U2W"
FT HELIX 70..82
FT /evidence="ECO:0007829|PDB:1U2W"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:1U2W"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:1U2W"
FT HELIX 102..115
FT /evidence="ECO:0007829|PDB:1U2W"
SQ SEQUENCE 122 AA; 13779 MW; 7C60BBAFFEB91BC6 CRC64;
MKKKDTCEIF CYDEEKVNRI QGDLQTVDIS GVSQILKAIA DENRAKITYA LCQDEELCVC
DIANILGVTI ANASHHLRTL YKQGVVNFRK EGKLALYSLG DEHIRQIMMI ALAHKKEVKV
NV
