P14146 (PHOP_SALTY) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Virulence transcriptional regulatory protein phoP

Gene names

Name:	phoP
Ordered Locus Names:	STM1231

Organism

Salmonella typhimurium

Taxonomic identifier

90371 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Salmonella

Protein attributes

Sequence length	224 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Member of the two-component regulatory system phoQ/phoP which regulates the expression of genes involved in virulence and resistance to host defense antimicrobial peptides. Promotes intramacrophage survival of S.typhimurium. Is essential for transcription of spiC inside macrophages by controlling the expression of the two-component regulatory system ssrB/spiR at transcriptional and post-transcriptional levels respectively. Promotes expression of the two-component regulatory system pmrA/pmrB via activation of pmrD gene. Is required to attenuate bacterial growth within fibroblast cells and to enhance bacterial resistance to bile in intestinal cells. Also, negatively regulates prgH, which is required for invasion of epithelial cells. PhoP uses multiple mechanisms to promote transcription and activates promoters for phoP-activated genes (PAG) at low (micromolar range) Mg2+ concentrations. Ref.5 Ref.8 Ref.9 Ref.10 Ref.13
Subcellular location	Cytoplasm Probable.
Induction	PhoQ/phoP operon is positively autoregulated by both phoP and phoQ in a Mg2+-dependent manner. Repressed by rcsB via sigma factor rpoS. Ref.6 Ref.7 Ref.10 Ref.12
Post-translational modification	Phosphorylated by phoQ Probable.
Miscellaneous	PhoQ/phoP-signaling cascade, which activated virulence membrane proteins (pagC, pagO, pagD, pagK, pgtE and phoN), is induced by cationic antimicrobial peptides (CAMP) (polymyxin, alpha-helical peptide C18G and sheet peptide protegrin-1) at sublethal concentrations.
Sequence similarities	Contains 1 response regulatory domain.

Ontologies

Keywords
Biological process	Growth regulation Transcription Transcription regulation Two-component regulatory system Virulence
Cellular component	Cytoplasm
Ligand	DNA-binding
Molecular function	Activator Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW regulation of growth Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW two-component response regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 224	224	Virulence transcriptional regulatory protein phoP		PRO_0000081201
Regions
	Domain	1 – 117	117	Response regulatory
Amino acid modifications
	Modified residue	52	1	4-aspartylphosphate By similarity
Experimental info
	Mutagenesis	52	1	D → A: Expression at concentrations above 30 micromolar retains a protein-protein interaction and phoQ-independent induction of PAG. Yields insoluble purified protein above 7 micromolar. Ref.11

Sequences

	Sequence		Length	Mass (Da)
	P14146 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: 3A90B2FDC328C7B2	FASTA	224	25,633
	10 20 30 40 50 60 MMRVLVVEDN ALLRHHLKVQ LQDSGHQVDA AEDAREADYY LNEHLPDIAI VDLGLPDEDG 70 80 90 100 110 120 LSLIRRWRSS DVSLPVLVLT AREGWQDKVE VLSSGADDYV TKPFHIEEVM ARMQALMRRN 130 140 150 160 170 180 SGLASQVINI PPFQVDLSRR ELSVNEEVIK LTAFEYTIME TLIRNNGKVV SKDSLMLQLY 190 200 210 220 PDAELRESHT IDVLMGRLRK KIQAQYPHDV ITTVRGQGYL FELR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence." Miller S.I., Kukral A.M., Mekalanos J.J. Proc. Natl. Acad. Sci. U.S.A. 86:5054-5058(1989) [PubMed: 2544889] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 14028 / SGSG 2980 / CDC 6516-60 / NCTC 12023.
[2]	"Salmonella typhimurium phoP virulence gene is a transcriptional regulator." Groisman E.A., Chiao E., Lipps C.J., Heffron F. Proc. Natl. Acad. Sci. U.S.A. 86:7077-7081(1989) [PubMed: 2674945] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Salmonella enterica serovar Typhimurium response involved in attenuation of pathogen intracellular proliferation." Cano D.A., Martinez-Moya M., Pucciarelli M.G., Groisman E.A., Casadesus J., Garcia-del Portillo F. Infect. Immun. 69:6463-6474(2001) [PubMed: 11553591] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: SL1344.
[4]	"Complete genome sequence of Salmonella enterica serovar Typhimurium LT2." McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P., Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D., Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E. , Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R., Wilson R.K. Nature 413:852-856(2001) [PubMed: 11677609] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: LT2 / SGSC1412 / ATCC 700720.
[5]	"A PhoP-repressed gene promotes Salmonella typhimurium invasion of epithelial cells." Behlau I., Miller S.I. J. Bacteriol. 175:4475-4484(1993) [PubMed: 8392513] [Abstract] Cited for: FUNCTION. Strain: ATCC 14028s / SGSG 2262.
[6]	"Transcriptional autoregulation of the Salmonella typhimurium phoPQ operon." Soncini F.C., Garcia Vescovi E., Groisman E.A. J. Bacteriol. 177:4364-4371(1995) [PubMed: 7543474] [Abstract] Cited for: AUTOREGULATION. Strain: ATCC 14028s / SGSG 2262.
[7]	"Mg2+ as an extracellular signal: environmental regulation of Salmonella virulence." Garcia Vescovi E., Soncini F.C., Groisman E.A. Cell 84:165-174(1996) [PubMed: 8548821] [Abstract] Cited for: REGULATION BY MG(2+). Strain: ATCC 14028s / SGSG 2262.
[8]	"PhoP-PhoQ-regulated loci are required for enhanced bile resistance in Salmonella spp." van Velkinburgh J.C., Gunn J.S. Infect. Immun. 67:1614-1622(1999) [PubMed: 10084994] [Abstract] Cited for: FUNCTION. Strain: ATCC 14028s / SGSG 2262.
[9]	"A small protein that mediates the activation of a two-component system by another two-component system." Kox L.F.F., Woesten M.M.S.M., Groisman E.A. EMBO J. 19:1861-1872(2000) [PubMed: 10775270] [Abstract] Cited for: FUNCTION. Strain: ATCC 14028s / SGSG 2262.
[10]	"Regulation of Salmonella typhimurium virulence gene expression by cationic antimicrobial peptides." Bader M.W., Navarre W.W., Shiau W., Nikaido H., Frye J.G., McClelland M., Fang F.C., Miller S.I. Mol. Microbiol. 50:219-230(2003) [PubMed: 14507376] [Abstract] Cited for: FUNCTION, REGULATION BY CATIONIC ANTIMICROBIAL PEPTIDES (CAMP). Strain: ATCC 14028s / SGSG 2262.
[11]	"PhoP can activate its target genes in a PhoQ-independent manner." Lejona S., Castelli M.E., Cabeza M.L., Kenney L.J., Garcia Vescovi E., Soncini F.C. J. Bacteriol. 186:2476-2480(2004) [PubMed: 15060051] [Abstract] Cited for: EFFECT OF PHOP OVEREXPRESSION, MUTAGENESIS OF ASP-52. Strain: ATCC 14028 / SGSG 2980 / CDC 6516-60 / NCTC 12023.
[12]	"The Salmonella membrane protein IgaA modulates the activity of the RcsC-YojN-RcsB and PhoP-PhoQ regulons." Tierrez A., Garcia-del Portillo F. J. Bacteriol. 186:7481-7489(2004) [PubMed: 15516559] [Abstract] Cited for: REGULATION BY RCSB. Strain: SL1344.
[13]	"The PhoP/PhoQ system controls the intramacrophage type three secretion system of Salmonella enterica." Bijlsma J.J.E., Groisman E.A. Mol. Microbiol. 57:85-96(2005) [PubMed: 15948951] [Abstract] Cited for: FUNCTION. Strain: ATCC 14028s / SGSG 2262.
[14]	"Dissecting the PhoP regulatory network of Escherichia coli and Salmonella enterica." Zwir I., Shin D., Kato A., Nishino K., Latifi T., Solomon F., Hare J.M., Huang H., Groisman E.A. Proc. Natl. Acad. Sci. U.S.A. 102:2862-2867(2005) [PubMed: 15703297] [Abstract] Cited for: ANALYSIS OF PHOP REGULATORY NETWORK.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M24424 Genomic DNA. Translation: AAA27188.1. M25241 Genomic DNA. Translation: AAA27187.1. AJ272210 Genomic DNA. Translation: CAB75591.1. AE006468 Genomic DNA. Translation: AAL20160.1.
PIR	RGEBFT. A32932.
RefSeq	NP_460201.1. NC_003197.1.
3D structure databases
ProteinModelPortal	P14146.
SMR	P14146. Positions 2-121.
ModBase	Search...
Proteomic databases
PRIDE	P14146.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	1252749.
GenomeReviews	Gene locus STM1231 in contig AE006468_GR.
KEGG	stm:STM1231.
PATRIC	32380915. VBISalEnt20916_1302.
Phylogenomic databases
HOGENOM	HBG753323.
OMA	SKESLML.
ProtClustDB	PRK10816.
Enzyme and pathway databases
BioCyc	STYP99287:STM1231-MONOMER.
Family and domain databases
InterPro	IPR011006. CheY-like_superfamily. IPR001867. Sig_transdc_resp-reg_C. IPR001789. Sig_transdc_resp-reg_receiver. IPR011991. WHTH_trsnscrt_rep_DNA-bd. [Graphical view]
Gene3D	G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
KO	K07660.
Pfam	PF00072. Response_reg. 1 hit. PF00486. Trans_reg_C. 1 hit. [Graphical view]
SMART	SM00448. REC. 1 hit. SM00862. Trans_reg_C. 1 hit. [Graphical view]
SUPFAM	SSF52172. CheY_like. 1 hit.
PROSITE	PS50110. RESPONSE_REGULATORY. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

PHOP_SALTY

Accession

Primary (citable) accession number: P14146

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	January 25, 2012
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program