GRAR_STAA8
ID GRAR_STAA8 Reviewed; 224 AA.
AC Q2G0E0;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 25-MAY-2022, entry version 100.
DE RecName: Full=Response regulator protein GraR {ECO:0000303|PubMed:17676995};
DE AltName: Full=Glycopeptide resistance-associated protein R;
GN Name=graR {ECO:0000303|PubMed:17676995}; OrderedLocusNames=SAOUHSC_00665;
OS Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC Bacteria; Firmicutes; 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 IN CATIONIC ANTIMICROBIAL PEPTIDE RESISTANCE.
RX PubMed=17502406; DOI=10.1128/aac.00209-07;
RA Meehl M., Herbert S., Goetz F., Cheung A.;
RT "Interaction of the graRS two-component system with the vraFG ABC
RT transporter to support vancomycin-intermediate resistance in Staphylococcus
RT aureus.";
RL Antimicrob. Agents Chemother. 51:2679-2689(2007).
RN [3]
RP FUNCTION AS A GLOBAL REGULATOR.
RX PubMed=17676995; DOI=10.1371/journal.ppat.0030102;
RA Herbert S., Bera A., Nerz C., Kraus D., Peschel A., Goerke C., Meehl M.,
RA Cheung A., Goetz F.;
RT "Molecular basis of resistance to muramidase and cationic antimicrobial
RT peptide activity of lysozyme in staphylococci.";
RL PLoS Pathog. 3:981-994(2007).
RN [4]
RP FUNCTION IN CATIONIC ANTIMICROBIAL PEPTIDE RESISTANCE.
RX PubMed=18518949; DOI=10.1186/1471-2180-8-85;
RA Kraus D., Herbert S., Kristian S.A., Khosravi A., Nizet V., Goetz F.,
RA Peschel A.;
RT "The graRS regulatory system controls Staphylococcus aureus susceptibility
RT to antimicrobial host defenses.";
RL BMC Microbiol. 8:85-85(2008).
RN [5]
RP FUNCTION, PHOSPHORYLATION AT THR-128; THR-130 AND THR-149, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=24102310; DOI=10.1021/bi401177n;
RA Fridman M., Williams G.D., Muzamal U., Hunter H., Siu K.W.,
RA Golemi-Kotra D.;
RT "Two unique phosphorylation-driven signaling pathways crosstalk in
RT Staphylococcus aureus to modulate the cell-wall charge: Stk1/Stp1 meets
RT GraSR.";
RL Biochemistry 52:7975-7986(2013).
RN [6]
RP FUNCTION, AND INTERACTION WITH GRAX.
RX PubMed=25685323; DOI=10.12688/f1000research.5512.2;
RA Muzamal U., Gomez D., Kapadia F., Golemi-Kotra D.;
RT "Diversity of two-component systems: insights into the signal transduction
RT mechanism by the Staphylococcus aureus two-component system GraSR.";
RL F1000Research 3:252-252(2014).
CC -!- FUNCTION: Member of the two-component regulatory system GraR/GraS
CC involved in resistance against cationic antimicrobial peptides (CAMPs)
CC (PubMed:17502406). Upon phosphorylation by GraS, functions as a
CC transcription regulator by direct binding to promoter regions of target
CC genes such as adhesins, exoproteins, transporters, toxins, and proteins
CC involved in cell wall synthesis. Down-regulates the expression of many
CC genes involved in RNA and amino acid synthesis or glycolysis
CC (PubMed:17676995, PubMed:18518949, PubMed:24102310, PubMed:25685323).
CC {ECO:0000269|PubMed:17502406, ECO:0000269|PubMed:17676995,
CC ECO:0000269|PubMed:18518949, ECO:0000269|PubMed:24102310,
CC ECO:0000269|PubMed:25685323}.
CC -!- SUBUNIT: Interacts with GraX. {ECO:0000269|PubMed:25685323}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- PTM: Phosphorylated by GraS. Phosphorylated by Stk1; phosphorylation
CC increases the DNA-binding activity of GraR.
CC {ECO:0000269|PubMed:24102310}.
CC -!- DISRUPTION PHENOTYPE: Decreases the resistance to vancomycin about 2-
CC fold. {ECO:0000269|PubMed:24102310}.
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DR EMBL; CP000253; ABD29798.1; -; Genomic_DNA.
DR RefSeq; WP_001166505.1; NZ_LS483365.1.
DR RefSeq; YP_499224.1; NC_007795.1.
DR AlphaFoldDB; Q2G0E0; -.
DR SMR; Q2G0E0; -.
DR STRING; 1280.SAXN108_0726; -.
DR EnsemblBacteria; ABD29798; ABD29798; SAOUHSC_00665.
DR GeneID; 3919955; -.
DR KEGG; sao:SAOUHSC_00665; -.
DR PATRIC; fig|93061.5.peg.596; -.
DR eggNOG; COG0745; Bacteria.
DR HOGENOM; CLU_000445_30_3_9; -.
DR OMA; QIISEVW; -.
DR PRO; PR:Q2G0E0; -.
DR Proteomes; UP000008816; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR CDD; cd00383; trans_reg_C; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR011006; CheY-like_superfamily.
DR InterPro; IPR001867; OmpR/PhoB-type_DNA-bd.
DR InterPro; IPR016032; Sig_transdc_resp-reg_C-effctor.
DR InterPro; IPR001789; Sig_transdc_resp-reg_receiver.
DR InterPro; IPR039420; WalR-like.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR PANTHER; PTHR48111; PTHR48111; 1.
DR Pfam; PF00072; Response_reg; 1.
DR Pfam; PF00486; Trans_reg_C; 1.
DR SMART; SM00448; REC; 1.
DR SMART; SM00862; Trans_reg_C; 1.
DR SUPFAM; SSF46894; SSF46894; 1.
DR SUPFAM; SSF52172; SSF52172; 1.
DR PROSITE; PS51755; OMPR_PHOB; 1.
DR PROSITE; PS50110; RESPONSE_REGULATORY; 1.
PE 1: Evidence at protein level;
KW Activator; Antibiotic resistance; Cytoplasm; DNA-binding; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Two-component regulatory system; Virulence.
FT CHAIN 1..224
FT /note="Response regulator protein GraR"
FT /id="PRO_0000347905"
FT DOMAIN 2..115
FT /note="Response regulatory"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT DNA_BIND 126..224
FT /note="OmpR/PhoB-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01091"
FT MOD_RES 51
FT /note="4-aspartylphosphate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT MOD_RES 128
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:24102310"
FT MOD_RES 130
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:24102310"
FT MOD_RES 149
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:24102310"
SQ SEQUENCE 224 AA; 26079 MW; 50D2DCBAB6EBD323 CRC64;
MQILLVEDDN TLFQELKKEL EQWDFNVAGI EDFGKVMDTF ESFNPEIVIL DVQLPKYDGF
YWCRKMREVS NVPILFLSSR DNPMDQVMSM ELGADDYMQK PFYTNVLIAK LQAIYRRVYE
FTAEEKRTLT WQDAVVDLSK DSIQKGDQTI FLSKTEMIIL EILITKKNQI VSRDTIITAL
WDDEAFVSDN TLTVNVNRLR KKLSEISMDS AIETKVGKGY MAHE
