VRAR_STAAM
ID VRAR_STAAM Reviewed; 209 AA.
AC Q7A2Q1;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Response regulator protein VraR;
GN Name=vraR; OrderedLocusNames=SAV1884;
OS Staphylococcus aureus (strain Mu50 / ATCC 700699).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=158878;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Mu50 / ATCC 700699;
RX PubMed=11418146; DOI=10.1016/s0140-6736(00)04403-2;
RA Kuroda M., Ohta T., Uchiyama I., Baba T., Yuzawa H., Kobayashi I., Cui L.,
RA Oguchi A., Aoki K., Nagai Y., Lian J.-Q., Ito T., Kanamori M.,
RA Matsumaru H., Maruyama A., Murakami H., Hosoyama A., Mizutani-Ui Y.,
RA Takahashi N.K., Sawano T., Inoue R., Kaito C., Sekimizu K., Hirakawa H.,
RA Kuhara S., Goto S., Yabuzaki J., Kanehisa M., Yamashita A., Oshima K.,
RA Furuya K., Yoshino C., Shiba T., Hattori M., Ogasawara N., Hayashi H.,
RA Hiramatsu K.;
RT "Whole genome sequencing of meticillin-resistant Staphylococcus aureus.";
RL Lancet 357:1225-1240(2001).
RN [2]
RP FUNCTION.
RX PubMed=10708580; DOI=10.1006/bbrc.2000.2277;
RA Kuroda M., Kuwahara-Arai K., Hiramatsu K.;
RT "Identification of the up- and down-regulated genes in vancomycin-resistant
RT Staphylococcus aureus strains Mu3 and Mu50 by cDNA differential
RT hybridization method.";
RL Biochem. Biophys. Res. Commun. 269:485-490(2000).
RN [3]
RP FUNCTION, PHOSPHORYLATION AT ASP-55, SUBUNIT, AND MUTAGENESIS OF ASP-55.
RC STRAIN=Mu50 / ATCC 700699;
RX PubMed=18326495; DOI=10.1074/jbc.m710010200;
RA Belcheva A., Golemi-Kotra D.;
RT "A close-up view of the VraSR two-component system. A mediator of
RT Staphylococcus aureus response to cell wall damage.";
RL J. Biol. Chem. 283:12354-12364(2008).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 2-209, PHOSPHORYLATION, FUNCTION,
RP AND SUBUNIT.
RX PubMed=23650349; DOI=10.1073/pnas.1302819110;
RA Leonard P.G., Golemi-Kotra D., Stock A.M.;
RT "Phosphorylation-dependent conformational changes and domain rearrangements
RT in Staphylococcus aureus VraR activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:8525-8530(2013).
RN [5]
RP STRUCTURE BY NMR OF 138-209, AND SUBUNIT.
RX PubMed=18293926; DOI=10.1021/bi701844q;
RA Donaldson L.W.;
RT "The NMR structure of the Staphylococcus aureus response regulator VraR DNA
RT binding domain reveals a dynamic relationship between it and its associated
RT receiver domain.";
RL Biochemistry 47:3379-3388(2008).
CC -!- FUNCTION: Member of the two-component regulatory system VraS/VraR
CC involved in the control of the cell wall peptidoglycan biosynthesis.
CC Upon cellular stress, the histidine kinase VraS transfers the
CC phosphoryl group onto VraR (PubMed:18326495). Upon phosphorylation,
CC VraR dimerizes at the N-terminal domain (PubMed:23650349,
CC PubMed:18326495). In turn, phosphorylation-induced dimerization expands
CC and enhances the VraR binding to its own promoter leading to increased
CC expression and subsequent modulation of about 40 genes, which
CC ultimately constitute the S.aureus response to cell wall damage
CC (PubMed:10708580). In addition, inhibits the host autophagic flux and
CC delays the early stage of autophagosome formation, thereby promoting
CC bacterial survival. Facilitates the ability of S.aureus to resist host
CC polymorphonuclear leukocytes-mediated phagocytosis and killing thus
CC contributing to immune evasion (By similarity).
CC {ECO:0000250|UniProtKB:P0C0Z1, ECO:0000269|PubMed:10708580,
CC ECO:0000269|PubMed:18326495, ECO:0000269|PubMed:23650349}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18293926,
CC ECO:0000269|PubMed:18326495, ECO:0000269|PubMed:23650349}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- PTM: Phosphorylated by VraS. Phosphorylation state of VraR controls
CC dimerization of the protein. {ECO:0000269|PubMed:18326495,
CC ECO:0000269|PubMed:23650349}.
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DR EMBL; BA000017; BAB58046.1; -; Genomic_DNA.
DR RefSeq; WP_000153535.1; NC_002758.2.
DR PDB; 2RNJ; NMR; -; A=138-209.
DR PDB; 4GVP; X-ray; 2.03 A; A/B/C/D=2-209.
DR PDB; 4IF4; X-ray; 2.35 A; A/B/C/D=2-209.
DR PDBsum; 2RNJ; -.
DR PDBsum; 4GVP; -.
DR PDBsum; 4IF4; -.
DR AlphaFoldDB; Q7A2Q1; -.
DR SMR; Q7A2Q1; -.
DR World-2DPAGE; 0002:Q7A2Q1; -.
DR PaxDb; Q7A2Q1; -.
DR EnsemblBacteria; BAB58046; BAB58046; SAV1884.
DR KEGG; sav:SAV1884; -.
DR HOGENOM; CLU_000445_90_10_9; -.
DR OMA; NVLRKTQ; -.
DR PhylomeDB; Q7A2Q1; -.
DR BioCyc; SAUR158878:SAV_RS10310-MON; -.
DR EvolutionaryTrace; Q7A2Q1; -.
DR Proteomes; UP000002481; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000160; P:phosphorelay signal transduction system; IEA:UniProtKB-KW.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR CDD; cd06170; LuxR_C_like; 1.
DR InterPro; IPR011006; CheY-like_superfamily.
DR InterPro; IPR016032; Sig_transdc_resp-reg_C-effctor.
DR InterPro; IPR001789; Sig_transdc_resp-reg_receiver.
DR InterPro; IPR000792; Tscrpt_reg_LuxR_C.
DR Pfam; PF00196; GerE; 1.
DR Pfam; PF00072; Response_reg; 1.
DR PRINTS; PR00038; HTHLUXR.
DR SMART; SM00421; HTH_LUXR; 1.
DR SMART; SM00448; REC; 1.
DR SUPFAM; SSF46894; SSF46894; 1.
DR SUPFAM; SSF52172; SSF52172; 1.
DR PROSITE; PS50043; HTH_LUXR_2; 1.
DR PROSITE; PS50110; RESPONSE_REGULATORY; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Antibiotic resistance; Cytoplasm; DNA-binding;
KW Phosphoprotein; Transcription; Transcription regulation;
KW Two-component regulatory system.
FT CHAIN 1..209
FT /note="Response regulator protein VraR"
FT /id="PRO_0000081270"
FT DOMAIN 4..120
FT /note="Response regulatory"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT DOMAIN 141..206
FT /note="HTH luxR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00411"
FT DNA_BIND 165..184
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00411"
FT MOD_RES 55
FT /note="4-aspartylphosphate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169,
FT ECO:0000269|PubMed:18326495"
FT MUTAGEN 55
FT /note="D->A: Complete loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:18326495"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:4GVP"
FT HELIX 12..24
FT /evidence="ECO:0007829|PDB:4GVP"
FT STRAND 28..36
FT /evidence="ECO:0007829|PDB:4GVP"
FT HELIX 37..47
FT /evidence="ECO:0007829|PDB:4GVP"
FT STRAND 50..57
FT /evidence="ECO:0007829|PDB:4GVP"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:4GVP"
FT HELIX 63..71
FT /evidence="ECO:0007829|PDB:4GVP"
FT STRAND 77..84
FT /evidence="ECO:0007829|PDB:4GVP"
FT HELIX 88..96
FT /evidence="ECO:0007829|PDB:4GVP"
FT STRAND 101..104
FT /evidence="ECO:0007829|PDB:4GVP"
FT HELIX 109..120
FT /evidence="ECO:0007829|PDB:4GVP"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:4GVP"
FT HELIX 131..143
FT /evidence="ECO:0007829|PDB:4GVP"
FT HELIX 144..147
FT /evidence="ECO:0007829|PDB:4GVP"
FT HELIX 150..160
FT /evidence="ECO:0007829|PDB:4GVP"
FT HELIX 165..172
FT /evidence="ECO:0007829|PDB:4GVP"
FT HELIX 176..189
FT /evidence="ECO:0007829|PDB:4GVP"
FT HELIX 195..204
FT /evidence="ECO:0007829|PDB:4GVP"
SQ SEQUENCE 209 AA; 23559 MW; 52984CE9494925B1 CRC64;
MTIKVLFVDD HEMVRIGISS YLSTQSDIEV VGEGASGKEA IAKAHELKPD LILMDLLMED
MDGVEATTQI KKDLPQIKVL MLTSFIEDKE VYRALDAGVD SYILKTTSAK DIADAVRKTS
RGESVFEPEV LVKMRNRMKK RAELYEMLTE REMEILLLIA KGYSNQEIAS ASHITIKTVK
THVSNILSKL EVQDRTQAVI YAFQHNLIQ