ID CODY_STAA8 Reviewed; 257 AA.
AC Q2FZ27;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 27-MAR-2024, entry version 114.
DE RecName: Full=Global transcriptional regulator CodY {ECO:0000255|HAMAP-Rule:MF_00621, ECO:0000305};
GN Name=codY {ECO:0000255|HAMAP-Rule:MF_00621, ECO:0000303|PubMed:18156263};
GN OrderedLocusNames=SAOUHSC_01228;
OS Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC Bacteria; Bacillota; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=93061;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NCTC 8325 / PS 47;
RA Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J.;
RT "The Staphylococcus aureus NCTC 8325 genome.";
RL (In) Fischetti V., Novick R., Ferretti J., Portnoy D., Rood J. (eds.);
RL Gram positive pathogens, 2nd edition, pp.381-412, ASM Press, Washington
RL D.C. (2006).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=clinical isolates, and RN4220;
RX PubMed=18156263; DOI=10.1128/jb.01545-07;
RA Majerczyk C.D., Sadykov M.R., Luong T.T., Lee C., Somerville G.A.,
RA Sonenshein A.L.;
RT "Staphylococcus aureus CodY negatively regulates virulence gene
RT expression.";
RL J. Bacteriol. 190:2257-2265(2008).
RN [3]
RP FUNCTION, ACTIVITY REGULATION BY ISOLEUCINE, AND DISRUPTION PHENOTYPE.
RC STRAIN=Newman, RN1HG, and UAMS-1;
RX PubMed=19251851; DOI=10.1128/jb.01492-08;
RA Pohl K., Francois P., Stenz L., Schlink F., Geiger T., Herbert S.,
RA Goerke C., Schrenzel J., Wolz C.;
RT "CodY in Staphylococcus aureus: a regulatory link between metabolism and
RT virulence gene expression.";
RL J. Bacteriol. 191:2953-2963(2009).
RN [4]
RP ERRATUM OF PUBMED:19251851.
RX DOI=10.1128/jb.00542-09;
RA Pohl K., Francois P., Stenz L., Schlink F., Geiger T., Herbert S.,
RA Goerke C., Schrenzel J., Wolz C.;
RL J. Bacteriol. 191:4695-4695(2009).
RN [5]
RP FUNCTION, DNA-BINDING, AND ACTIVITY REGULATION.
RC STRAIN=NCTC 8325 / PS 47, and UAMS-1;
RX PubMed=20363936; DOI=10.1128/jb.00220-10;
RA Majerczyk C.D., Dunman P.M., Luong T.T., Lee C.Y., Sadykov M.R.,
RA Somerville G.A., Bodi K., Sonenshein A.L.;
RT "Direct targets of CodY in Staphylococcus aureus.";
RL J. Bacteriol. 192:2861-2877(2010).
RN [6]
RP FUNCTION, AND ACTIVITY REGULATION.
RC STRAIN=UAMS-1;
RX PubMed=27116338; DOI=10.1111/mmi.13404;
RA Waters N.R., Samuels D.J., Behera R.K., Livny J., Rhee K.Y., Sadykov M.R.,
RA Brinsmade S.R.;
RT "A spectrum of CodY activities drives metabolic reorganization and
RT virulence gene expression in Staphylococcus aureus.";
RL Mol. Microbiol. 101:495-514(2016).
RN [7]
RP FUNCTION.
RX PubMed=29378891; DOI=10.1128/jb.00012-18;
RA Mlynek K.D., Sause W.E., Moormeier D.E., Sadykov M.R., Hill K.R.,
RA Torres V.J., Bayles K.W., Brinsmade S.R.;
RT "Nutritional regulation of the Sae two-component system by CodY in
RT Staphylococcus aureus.";
RL J. Bacteriol. 200:e00012-e00012(2018).
RN [8]
RP FUNCTION, AND ACTIVITY REGULATION.
RC STRAIN=RN4220, and USA300;
RX PubMed=29357354; DOI=10.1371/journal.pgen.1007159;
RA Kaiser J.C., King A.N., Grigg J.C., Sheldon J.R., Edgell D.R.,
RA Murphy M.E.P., Brinsmade S.R., Heinrichs D.E.;
RT "Repression of branched-chain amino acid synthesis in Staphylococcus aureus
RT is mediated by isoleucine via CodY, and by a leucine-rich attenuator
RT peptide.";
RL PLoS Genet. 14:e1007159-e1007159(2018).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=UAMS-1;
RX PubMed=35735992; DOI=10.1128/jb.00617-21;
RA Bulock L.L., Ahn J., Shinde D., Pandey S., Sarmiento C., Thomas V.C.,
RA Guda C., Bayles K.W., Sadykov M.R.;
RT "Interplay of CodY and CcpA in regulating central metabolism and biofilm
RT formation in Staphylococcus aureus.";
RL J. Bacteriol. 204:e0061721-e0061721(2022).
RN [10]
RP REVIEW.
RX PubMed=27744611; DOI=10.1007/s00294-016-0656-5;
RA Brinsmade S.R.;
RT "CodY, a master integrator of metabolism and virulence in Gram-positive
RT bacteria.";
RL Curr. Genet. 63:417-425(2017).
CC -!- FUNCTION: DNA-binding global transcriptional regulator which is
CC involved in the adaptive response to starvation and acts by directly or
CC indirectly controlling the expression of numerous genes in response to
CC nutrient availability. During rapid exponential growth, CodY is highly
CC active and represses genes whose products allow adaptation to nutrient
CC depletion. {ECO:0000255|HAMAP-Rule:MF_00621,
CC ECO:0000269|PubMed:27116338}.
CC -!- FUNCTION: In S.aureus, targets include over 200 genes (PubMed:20363936,
CC PubMed:27116338). Acts mainly as a repressor of genes involved in amino
CC acid transport and metabolism, including the branched-chain amino acids
CC (BCAAs) biosynthetic operon (PubMed:19251851, PubMed:20363936,
CC PubMed:27116338, PubMed:29357354). Several genes involved in nucleotide
CC synthesis and transport are activated (PubMed:19251851). Binds to a 21-
CC bp conserved DNA motif, the CodY-binding site (PubMed:20363936).
CC Additionally, in pathogenic bacteria, CodY also regulates virulence
CC gene expression and provides a regulatory link between metabolism and
CC pathogenesis (PubMed:18156263, PubMed:19251851, PubMed:20363936,
CC PubMed:27116338, PubMed:29378891). Genes encoding virulence and defense
CC factors are either up- or down-regulated by CodY (PubMed:19251851).
CC Among others, is involved in the repression of the accessory gene
CC regulator (agr), the hemolytic alpha-toxin (hla) gene, and the icaADBC
CC operon, responsible for the production of polysaccharide intercellular
CC adhesin (PIA), a major contributor to biofilm formation in S.aureus
CC (PubMed:18156263, PubMed:19251851). Also regulates the expression of
CC thermonuclease (nuc) via the Sae two-component system, by binding
CC directly to the sae P1 promoter region and blocking the binding of the
CC positive regulator SaeR (PubMed:27116338, PubMed:29378891). It
CC restrains Sae-dependent production of leukocidins (PubMed:29378891).
CC CodY also controls the sae locus indirectly through Agr and Rot-
CC mediated repression of the sae P1 promoter (PubMed:29378891). The
CC virulence genes regulated by CodY fall into three groups: one group is
CC regulated directly by CodY, a second group is indirectly regulated by
CC CodY, in particular through its repression of the agr and sae loci, and
CC a third group is regulated in two ways, by direct repression and by
CC repression via another regulator (PubMed:19251851, PubMed:20363936,
CC PubMed:29378891). S.aureus may use CodY to limit host damage to only
CC the most severe starvation conditions (PubMed:27116338). Modulation of
CC central metabolism, virulence gene expression, and biofilm-associated
CC genes to optimize growth on preferred carbon sources until starvation
CC sets in may require coordinated action of CodY and the carbon
CC catabolite protein A (CcpA), another global transcriptional regulator
CC (PubMed:35735992). {ECO:0000269|PubMed:18156263,
CC ECO:0000269|PubMed:19251851, ECO:0000269|PubMed:20363936,
CC ECO:0000269|PubMed:27116338, ECO:0000269|PubMed:29357354,
CC ECO:0000269|PubMed:29378891, ECO:0000269|PubMed:35735992}.
CC -!- ACTIVITY REGULATION: Activity of CodY is modulated by interaction with
CC two types of effectors: the branched-chain amino acids (BCAAs) leucine,
CC isoleucine and valine, which are signals of the nutritional status of
CC the cell, and GTP, which may signal the energetic status of the cell
CC (PubMed:20363936, PubMed:27116338, PubMed:29357354). GTP and the BCAAs
CC act additively to increase the affinity of CodY for DNA
CC (PubMed:20363936). Isoleucine could be a major signal for CodY
CC regulation in comparison to other BCAAs (PubMed:19251851,
CC PubMed:29357354). {ECO:0000269|PubMed:19251851,
CC ECO:0000269|PubMed:20363936, ECO:0000269|PubMed:27116338,
CC ECO:0000269|PubMed:29357354}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00621,
CC ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Disruption of the gene in two clinical isolates,
CC SA564 and UAMS-1, results in the overexpression of several virulence
CC genes (PubMed:18156263). The mutant strains have higher levels of
CC hemolytic activity toward rabbit erythrocytes in their culture fluid,
CC show derepressed transcription of the accessory gene regulator (agr)
CC locus, and derepressed PIA-dependent biofilm formation
CC (PubMed:18156263). Disruption results in a robust structured biofilm
CC tethered together with eDNA and PIA (PubMed:35735992). Mutants from
CC unrelated strains Newman, UAMS-1 and RN1HG grow more slowly than their
CC parent strains in a chemically defined medium, but only codY mutants
CC are able to grow in medium lacking threonine (PubMed:19251851).
CC {ECO:0000269|PubMed:18156263, ECO:0000269|PubMed:19251851,
CC ECO:0000269|PubMed:35735992}.
CC -!- SIMILARITY: Belongs to the CodY family. {ECO:0000255|HAMAP-
CC Rule:MF_00621}.
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DR EMBL; CP000253; ABD30331.1; -; Genomic_DNA.
DR RefSeq; WP_000055337.1; NZ_LS483365.1.
DR RefSeq; YP_499763.1; NC_007795.1.
DR AlphaFoldDB; Q2FZ27; -.
DR SMR; Q2FZ27; -.
DR STRING; 93061.SAOUHSC_01228; -.
DR PaxDb; 1280-SAXN108_1257; -.
DR GeneID; 3920255; -.
DR KEGG; sao:SAOUHSC_01228; -.
DR PATRIC; fig|93061.5.peg.1125; -.
DR eggNOG; COG4465; Bacteria.
DR HOGENOM; CLU_089581_0_0_9; -.
DR OrthoDB; 2056at2; -.
DR PHI-base; PHI:10203; -.
DR PRO; PR:Q2FZ27; -.
DR Proteomes; UP000008816; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IEA:UniProtKB-UniRule.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; IBA:GO_Central.
DR Gene3D; 3.30.450.40; -; 1.
DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR HAMAP; MF_00621; HTH_type_CodY; 1.
DR InterPro; IPR014154; CodY.
DR InterPro; IPR029016; GAF-like_dom_sf.
DR InterPro; IPR013198; GTP_trans_reg_CodY_C.
DR InterPro; IPR010312; Transc_reg_CodY_N.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR NCBIfam; TIGR02787; codY_Gpos; 1.
DR PANTHER; PTHR40062:SF1; GLOBAL TRANSCRIPTIONAL REGULATOR CODY; 1.
DR PANTHER; PTHR40062; GTP-SENSING TRANSCRIPTIONAL PLEIOTROPIC REPRESSOR CODY; 1.
DR Pfam; PF06018; CodY; 1.
DR Pfam; PF08222; HTH_CodY; 1.
DR PIRSF; PIRSF011572; GTP_sensing_CodY; 1.
DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; DNA-binding; GTP-binding; Nucleotide-binding;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..257
FT /note="Global transcriptional regulator CodY"
FT /id="PRO_1000051543"
FT DNA_BIND 203..222
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00621"
FT REGION 1..155
FT /note="GAF domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00621"
SQ SEQUENCE 257 AA; 28755 MW; B62509C4F2B8DE53 CRC64;
MSLLSKTREL NTLLQKHKGI AVDFKDVAQT ISSVTVTNVF IVSRRGKILG SSLNELLKSQ
RIIQMLEERH IPSEYTERLM EVKQTESNID IDNVLTVFPP ENRELFIDSR TTIFPILGGG
ERLGTLVLGR VHDDFNENDL VLGEYAATVI GMEILREKHS EVEKEARDKA AITMAINSLS
YSEKEAIEHI FEELGGTEGL LIASKVADRV GITRSVIVNA LRKLESAGVI ESRSLGMKGT
FIKVKKEKFL DELEKSK
//
