VFR_PSEAE
ID VFR_PSEAE Reviewed; 214 AA.
AC P55222;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=cAMP-activated global transcriptional regulator Vfr;
GN Name=vfr; OrderedLocusNames=PA0652;
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=8002577; DOI=10.1128/jb.176.24.7532-7542.1994;
RA West S.E.H., Sample A.K., Runyen-Janecky L.J.;
RT "The vfr gene product, required for Pseudomonas aeruginosa exotoxin A and
RT protease production, belongs to the cyclic AMP receptor protein family.";
RL J. Bacteriol. 176:7532-7542(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [3]
RP FUNCTION, AND DNA-BINDING.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=9190808; DOI=10.1128/jb.179.12.3928-3935.1997;
RA Albus A.M., Pesci E.C., Runyen-Janecky L.J., West S.E., Iglewski B.H.;
RT "Vfr controls quorum sensing in Pseudomonas aeruginosa.";
RL J. Bacteriol. 179:3928-3935(1997).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND ACTIVITY REGULATION.
RC STRAIN=PAK;
RX PubMed=12057955; DOI=10.1128/jb.184.13.3605-3613.2002;
RA Beatson S.A., Whitchurch C.B., Sargent J.L., Levesque R.C., Mattick J.S.;
RT "Differential regulation of twitching motility and elastase production by
RT Vfr in Pseudomonas aeruginosa.";
RL J. Bacteriol. 184:3605-3613(2002).
RN [5]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=17159200; DOI=10.1099/mic.0.29008-0;
RA Kanack K.J., Runyen-Janecky L.J., Ferrell E.P., Suh S.J., West S.E.H.;
RT "Characterization of DNA-binding specificity and analysis of binding sites
RT of the Pseudomonas aeruginosa global regulator, Vfr, a homologue of the
RT Escherichia coli cAMP receptor protein.";
RL Microbiology 152:3485-3496(2006).
RN [6]
RP FUNCTION.
RX PubMed=19389782; DOI=10.1099/mic.0.028373-0;
RA Davinic M., Carty N.L., Colmer-Hamood J.A., San Francisco M., Hamood A.N.;
RT "Role of Vfr in regulating exotoxin A production by Pseudomonas
RT aeruginosa.";
RL Microbiology 155:2265-2273(2009).
RN [7]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=20494996; DOI=10.1128/jb.00363-10;
RA Fuchs E.L., Brutinel E.D., Jones A.K., Fulcher N.B., Urbanowski M.L.,
RA Yahr T.L., Wolfgang M.C.;
RT "The Pseudomonas aeruginosa Vfr regulator controls global virulence factor
RT expression through cyclic AMP-dependent and -independent mechanisms.";
RL J. Bacteriol. 192:3553-3564(2010).
RN [8]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=25897033; DOI=10.1128/jb.00193-15;
RA Almblad H., Harrison J.J., Rybtke M., Groizeleau J., Givskov M.,
RA Parsek M.R., Tolker-Nielsen T.;
RT "The Cyclic AMP-Vfr Signaling Pathway in Pseudomonas aeruginosa Is
RT Inhibited by Cyclic Di-GMP.";
RL J. Bacteriol. 197:2190-2200(2015).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26929300; DOI=10.1128/jb.00049-16;
RA Marsden A.E., Intile P.J., Schulmeyer K.H., Simmons-Patterson E.R.,
RA Urbanowski M.L., Wolfgang M.C., Yahr T.L.;
RT "Vfr Directly Activates exsA Transcription To Regulate Expression of the
RT Pseudomonas aeruginosa Type III Secretion System.";
RL J. Bacteriol. 198:1442-1450(2016).
RN [10]
RP FUNCTION.
RC STRAIN=PAK;
RX PubMed=30761117; DOI=10.3389/fmicb.2019.00085;
RA Jin Y., Zhang M., Zhu F., Peng Q., Weng Y., Zhao Q., Liu C., Bai F.,
RA Cheng Z., Jin S., Wu W.;
RT "NrtR Regulates the Type III Secretion System Through cAMP/Vfr Pathway in
RT Pseudomonas aeruginosa.";
RL Front. Microbiol. 10:85-85(2019).
RN [11] {ECO:0007744|PDB:2OZ6}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 9-214 IN COMPLEX WITH CAMP,
RP SUBUNIT, AND DNA-BINDING.
RX PubMed=21665969; DOI=10.1128/jb.00666-10;
RA Cordes T.J., Worzalla G.A., Ginster A.M., Forest K.T.;
RT "Crystal structure of the Pseudomonas aeruginosa virulence factor
RT regulator.";
RL J. Bacteriol. 193:4069-4074(2011).
CC -!- FUNCTION: Global cAMP-dependent transcriptional regulator that controls
CC virulence gene expression by distinct cAMP-dependent and -independent
CC mechanisms, which allow to fine tune its virulence program in response
CC to specific host cues or environments (PubMed:20494996). Controls the
CC expression of many regulatory targets including type II, type III and
CC type IV secretion systems, flagellar-mediated motility, and quorum
CC sensing systems (PubMed:9190808, PubMed:12057955, PubMed:26929300,
CC PubMed:30761117). Transcriptional control is exerted by binding to a
CC well-characterized consensus site (5'-ANWWTGNGAWNYAGWTCACAT) within
CC target promoters (PubMed:17159200, PubMed:20494996, PubMed:26929300).
CC Directly binds to the toxA upstream region to regulate exotoxin A
CC production, to the lasR gene promoter to activate the las quorum-
CC sensing system or to the exsA promoter to regulate type III secretion
CC system (PubMed:9190808, PubMed:12057955, PubMed:19389782).
CC Autoregulates as well its own expression (PubMed:20494996).
CC {ECO:0000269|PubMed:12057955, ECO:0000269|PubMed:17159200,
CC ECO:0000269|PubMed:19389782, ECO:0000269|PubMed:20494996,
CC ECO:0000269|PubMed:26929300, ECO:0000269|PubMed:30761117,
CC ECO:0000269|PubMed:9190808}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:21665969}.
CC -!- INDUCTION: Regulated by both cAMP and cGMP to allow differential
CC regulation of different regulons (PubMed:12057955). Cyclic AMP is
CC required for Vfr binding to vfr, regA, ptxR, and cpdA promoter DNA
CC (PubMed:20494996, PubMed:25897033). Cyclic GMP instead inhibits the
CC formation of Vfr-DNA complexes (PubMed:20494996, PubMed:25897033).
CC {ECO:0000269|PubMed:12057955, ECO:0000269|PubMed:20494996,
CC ECO:0000269|PubMed:25897033}.
CC -!- DISRUPTION PHENOTYPE: Mutants show loss of twitching motility and are
CC defective in type IV pilus assembly (PubMed:12057955). Expression of
CC ExsA is also strongly affected in the mutant (PubMed:26929300).
CC {ECO:0000269|PubMed:12057955, ECO:0000269|PubMed:26929300}.
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DR EMBL; U16318; AAA73464.1; -; Genomic_DNA.
DR EMBL; AE004091; AAG04041.1; -; Genomic_DNA.
DR PIR; A55540; A55540.
DR RefSeq; NP_249343.1; NC_002516.2.
DR RefSeq; WP_003085214.1; NZ_QZGE01000010.1.
DR PDB; 2OZ6; X-ray; 2.80 A; A=9-214.
DR PDBsum; 2OZ6; -.
DR AlphaFoldDB; P55222; -.
DR SMR; P55222; -.
DR STRING; 287.DR97_3605; -.
DR PaxDb; P55222; -.
DR PRIDE; P55222; -.
DR DNASU; 880744; -.
DR EnsemblBacteria; AAG04041; AAG04041; PA0652.
DR GeneID; 880744; -.
DR KEGG; pae:PA0652; -.
DR PATRIC; fig|208964.12.peg.683; -.
DR PseudoCAP; PA0652; -.
DR HOGENOM; CLU_075053_3_5_6; -.
DR InParanoid; P55222; -.
DR OMA; VLCRDFG; -.
DR PhylomeDB; P55222; -.
DR BioCyc; PAER208964:G1FZ6-657-MON; -.
DR EvolutionaryTrace; P55222; -.
DR Proteomes; UP000002438; Chromosome.
DR CollecTF; EXPREG_00000b50; -.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0032993; C:protein-DNA complex; IMP:CollecTF.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; IMP:CollecTF.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0001217; F:DNA-binding transcription repressor activity; IMP:CollecTF.
DR GO; GO:0043565; F:sequence-specific DNA binding; IPI:CollecTF.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IMP:CollecTF.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:CollecTF.
DR GO; GO:0006351; P:transcription, DNA-templated; IMP:CACAO.
DR CDD; cd00038; CAP_ED; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR018488; cNMP-bd_CS.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR012318; HTH_CRP.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR018335; Tscrpt_reg_HTH_Crp-type_CS.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00027; cNMP_binding; 1.
DR Pfam; PF13545; HTH_Crp_2; 1.
DR PRINTS; PR00034; HTHCRP.
DR SMART; SM00100; cNMP; 1.
DR SMART; SM00419; HTH_CRP; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR PROSITE; PS00888; CNMP_BINDING_1; 1.
DR PROSITE; PS00889; CNMP_BINDING_2; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
DR PROSITE; PS00042; HTH_CRP_1; 1.
DR PROSITE; PS51063; HTH_CRP_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; cAMP; cAMP-binding; DNA-binding; Nucleotide-binding;
KW Reference proteome; Transcription; Transcription regulation; Virulence.
FT CHAIN 1..214
FT /note="cAMP-activated global transcriptional regulator Vfr"
FT /id="PRO_0000100189"
FT DOMAIN 142..214
FT /note="HTH crp-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00387"
FT DNA_BIND 174..193
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00387"
FT BINDING 59..60
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:21665969,
FT ECO:0007744|PDB:2OZ6"
FT BINDING 73..75
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:21665969,
FT ECO:0007744|PDB:2OZ6"
FT BINDING 87..88
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:21665969,
FT ECO:0007744|PDB:2OZ6"
FT BINDING 132..133
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:21665969,
FT ECO:0007744|PDB:2OZ6"
FT BINDING 179
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:21665969,
FT ECO:0007744|PDB:2OZ6"
FT BINDING 185
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:21665969,
FT ECO:0007744|PDB:2OZ6"
FT HELIX 10..18
FT /evidence="ECO:0007829|PDB:2OZ6"
FT STRAND 19..25
FT /evidence="ECO:0007829|PDB:2OZ6"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:2OZ6"
FT STRAND 40..54
FT /evidence="ECO:0007829|PDB:2OZ6"
FT STRAND 60..67
FT /evidence="ECO:0007829|PDB:2OZ6"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:2OZ6"
FT STRAND 89..95
FT /evidence="ECO:0007829|PDB:2OZ6"
FT STRAND 97..103
FT /evidence="ECO:0007829|PDB:2OZ6"
FT HELIX 104..113
FT /evidence="ECO:0007829|PDB:2OZ6"
FT HELIX 115..141
FT /evidence="ECO:0007829|PDB:2OZ6"
FT HELIX 144..155
FT /evidence="ECO:0007829|PDB:2OZ6"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:2OZ6"
FT STRAND 167..171
FT /evidence="ECO:0007829|PDB:2OZ6"
FT HELIX 174..181
FT /evidence="ECO:0007829|PDB:2OZ6"
FT HELIX 185..197
FT /evidence="ECO:0007829|PDB:2OZ6"
FT STRAND 200..204
FT /evidence="ECO:0007829|PDB:2OZ6"
FT STRAND 207..211
FT /evidence="ECO:0007829|PDB:2OZ6"
SQ SEQUENCE 214 AA; 24225 MW; 03B7F2A4C2CED7E6 CRC64;
MVAITHTPKL KHLDKLLAHC HRRRYTAKST IIYAGDRCET LFFIIKGSVT ILIEDDDGRE
MIIGYLNSGD FFGELGLFEK EGSEQERSAW VRAKVECEVA EISYAKFREL SQQDSEILYT
LGSQMADRLR KTTRKVGDLA FLDVTGRVAR TLLDLCQQPD AMTHPDGMQI KITRQEIGRI
VGCSREMVGR VLKSLEEQGL VHVKGKTMVV FGTR
