Detailed information NTG0000258

Experimentally validated

Overview

• Name: ciaR
• Type: Regulator
• Locus tag: KZH43_RS03475
• Genome accession: NZ_CP079923
• Coordinates: 703100..703774 (+)
• Length: 224 a.a.
• NCBI ID: WP_000590640.1
• Uniprot ID: D4I4V1
• Organism: Streptococcus pneumoniae Rx1
• Function: repress competence development; post-transcriptional repression of CSP production Competence regulation

Function

CiaRH negatively regulates competence development by controlling the expression of csRNAs (cia-dependent small RNAs) that target comC. These csRNAs post-transcriptionally regulate comC, thereby influencing the initiation of the competence cascade. A hyperactive CiaRH system might suppress competence development by increasing the level of HtrA at the outer surface of the cytoplasmic membrane.

Genomic Context

Location: 698100..708774

Locus tag	Gene name	Coordinates (strand)	Size (bp)	Protein ID	Product	Description
KZH43_RS03455 (KZH43_03460)	-	698268..698996 (+)	729	WP_000418692.1	GNAT family N-acetyltransferase	-
KZH43_RS03460 (KZH43_03465)	-	699038..699907 (+)	870	WP_000795797.1	putative PEP-binding protein	-
KZH43_RS03465 (KZH43_03470)	-	699882..700322 (+)	441	WP_001856133.1	ASCH domain-containing protein	-
KZH43_RS03470 (KZH43_03475)	-	700445..702991 (+)	2547	WP_001149118.1	M1 family metallopeptidase	-
KZH43_RS03475 (KZH43_03480)	ciaR	703100..703774 (+)	675	WP_000590640.1	two-component system response regulator CiaR	Regulator
KZH43_RS03480 (KZH43_03485)	ciaH	703764..705098 (+)	1335	WP_000491790.1	two-component system sensor histidine kinase CiaH	Regulator
KZH43_RS03485 (KZH43_03490)	-	705132..705419 (-)	288	WP_001145224.1	DUF3270 domain-containing protein	-
KZH43_RS03490 (KZH43_03495)	-	705559..706488 (+)	930	WP_000411858.1	peptidase U32 family protein	-

Regulatory network

Positive effect      

Negative effect

Regulator	Target	Regulation
ciaR	htrA	positive effect
htrA	comEA/celA/cilE	negative effect
htrA	comC/comC1	negative effect
comC/comC1	comD/comD1	positive effect
comB	comC/comC1	positive effect
ciaR	comC/comC1	negative effect
ciaH	comC/comC1	negative effect
comA	comC/comC1	positive effect
comE	comC/comC1	positive effect
htrA	comEC/celB	negative effect
ciaH	htrA	positive effect
comD/comD1	comE	positive effect
comE	comA	positive effect
comE	comB	positive effect
comE	comE	positive effect
comE	comX/comX1	positive effect
comE	comX/comX2	positive effect
comE	comD/comD1	positive effect
comE	comM	positive effect
comE	comW	positive effect
stkP	comE	positive effect
comX/comX1	late competence genes	positive effect
comW	comX/comX1	positive effect
clpE	comX/comX1	negative effect
clpP	comX/comX1	negative effect
comX/comX2	late competence genes	positive effect
comW	comX/comX2	positive effect
clpE	comX/comX2	negative effect
clpP	comX/comX2	negative effect
comM	cbpD	negative effect
clpC	comW	negative effect
clpP	comW	negative effect
mecA	comW	negative effect
comX/comX1	late competence genes	positive effect
comX/comX2	late competence genes	positive effect
cbpD	lytA	positive effect
cbpD	lytC	positive effect

Sequence

Protein

• Length: 224 a.a.
• Molecular weight: 25466.29 Da
• Isoelectric Point: 4.3283

>NTDB_id=258 KZH43_RS03475 WP_000590640.1 703100..703774(+) (ciaR) [Streptococcus pneumoniae Rx1]
MIKILLVEDDLGLSNSVFDFLDDFADVMQVFDGEEGLYEAESGVYDLILLDLMLPEKNGFQVLKELREKGITTPVLIMTA
KESLDDKGHGFELGADDYLTKPFYLEELKMRIQALLKRSGKFNENTLTYGNIVVNLSTNTVKVEDTPVELLGKEFDLLVY
FLQNQNVILPKTQIFDRLWGFDSDTTISVVEVYVSKVRKKLKGTTFAENLQTLRSVGYLLKDVQ

Nucleotide

• Length: 675 bp

>NTDB_id=258 KZH43_RS03475 WP_000590640.1 703100..703774(+) (ciaR) [Streptococcus pneumoniae Rx1]
ATGATAAAAATCTTATTGGTTGAGGATGACCTAGGTCTGTCAAATTCAGTATTTGACTTTTTAGACGATTTTGCGGATGT
TATGCAGGTATTTGATGGAGAAGAAGGTCTCTACGAAGCTGAGAGTGGTGTCTATGACTTGATTTTGCTGGATTTGATGT
TGCCAGAAAAAAATGGTTTCCAAGTCTTAAAAGAATTGCGTGAAAAGGGAATTACGACACCAGTTCTGATTATGACTGCC
AAGGAAAGTTTGGATGACAAGGGACATGGATTTGAACTGGGAGCGGATGATTATCTGACCAAACCTTTCTACCTAGAAGA
ACTTAAAATGCGGATTCAGGCCCTTCTCAAACGTTCAGGGAAGTTTAATGAAAACACCTTGACTTATGGGAATATCGTGG
TTAATTTATCAACCAATACCGTTAAAGTTGAAGATACTCCTGTCGAATTGCTGGGGAAAGAGTTCGATTTACTAGTTTAT
TTCCTTCAAAATCAAAATGTGATTTTGCCTAAGACGCAGATTTTTGACCGTCTATGGGGATTTGATAGTGATACAACGAT
TTCGGTTGTCGAAGTCTATGTTTCAAAAGTCCGTAAGAAATTAAAGGGAACCACTTTTGCAGAGAATTTGCAAACCTTGC
GTAGTGTTGGGTATCTTTTAAAAGATGTTCAGTAA

Domains

Predicted by InterproScan.

• Transcriptional regulatory protein, C terminal (Trans_reg_C) (146-220)

• Response regulator receiver domain (Response_reg) (4-112)

3D structure

• AlphaFold DB: D4I4V1

Similar proteins

Only experimentally validated proteins are listed.

Protein	Organism	Identities (%)	Coverage (%)	Ha-value
ciaR	Streptococcus pneumoniae TIGR4	100	100	1
ciaR	Streptococcus pneumoniae D39	100	100	1
ciaR	Streptococcus pneumoniae R6	100	100	1
ciaR	Streptococcus mutans UA159	88.393	100	0.884
covR	Lactococcus lactis subsp. lactis strain DGCC12653	36.726	100	0.371
vicR	Streptococcus mutans UA159	35.622	100	0.371

References

• [1]: Ozcan Gazioglu et al. (2023) The involvement of CiaR and the CiaR-regulated serine protease HtrA in thermal adaptation of Streptococcus pneumoniae. Microbiology (Reading, England) 169(2):001304. [PMID: 36811449]
• [2]: Sabrina Kaiser et al. (2020) Control of acetyl phosphate-dependent phosphorylation of the response regulator CiaR by acetate kinase in Streptococcus pneumoniae. Microbiology (Reading, England) 166(4):411-421. [PMID: 32553069]
• [3]: Anke Laux et al. (2015) Control of competence by related non-coding csRNAs in Streptococcus pneumoniae R6. Frontiers in Genetics 6:246. [PMID: 26257773]
• [4]: Anke Schnorpfeil et al. (2013) Target evaluation of the non-coding csRNAs reveals a link of the two-component regulatory system CiaRH to competence control in Streptococcus pneumoniae R6. Molecular Microbiology 89(2):334-49. [PMID: 23710838]
• [5]: Marco Cassone et al. (2012) The HtrA protease from Streptococcus pneumoniae digests both denatured proteins and the competence-stimulating peptide. The Journal of Biological Chemistry 287(46):38449-59. [PMID: 23012372]
• [6]: Alexander Halfmann et al. (2011) Activity of the two-component regulatory system CiaRH in Streptococcus pneumoniae R6. Journal of Molecular Microbiology And Biotechnology 20(2):96-104. [PMID: 21422763]
• [7]: Miriam Müller et al. (2011) Effect of new alleles of the histidine kinase gene ciaH on the activity of the response regulator CiaR in Streptococcus pneumoniae R6. Microbiology (Reading, England) 157(Pt 11):3104-3112. [PMID: 21903754]
• [8]: Patrick Marx et al. (2010) Identification of genes for small non-coding RNAs that belong to the regulon of the two-component regulatory system CiaRH in Streptococcus. BMC Genomics 11:661. [PMID: 21106082]
• [9]: Alexander Halfmann et al. (2007) Identification of the genes directly controlled by the response regulator CiaR in Streptococcus pneumoniae: five out of 15 promoters drive expression of small non-coding RNAs. Molecular Microbiology 66(1):110-26. [PMID: 17725562]
• [10]: M E Sebert et al. (2005) Pneumococcal HtrA protease mediates inhibition of competence by the CiaRH two-component signaling system. Journal of Bacteriology 187(12):3969-79. [PMID: 15937159]
• [11]: Adilia Dagkessamanskaia et al. (2004) Interconnection of competence, stress and CiaR regulons in Streptococcus pneumoniae: competence triggers stationary phase autolysis of ciaR mutant cells. Molecular Microbiology 51(4):1071-86. [PMID: 14763981]
• [12]: Yasser Musa Ibrahim et al. (2004) Control of virulence by the two-component system CiaR/H is mediated via HtrA, a major virulence factor of Streptococcus pneumoniae. Journal of Bacteriology 186(16):5258-66. [PMID: 15292127]
• [13]: Thorsten Mascher et al. (2003) The Streptococcus pneumoniae cia regulon: CiaR target sites and transcription profile analysis. Journal of Bacteriology 185(1):60-70. [PMID: 12486041]
• [14]: Dorothea Zähner et al. (2002) The ciaR/ciaH regulatory network of Streptococcus pneumoniae. Journal of Molecular Microbiology And Biotechnology 4(3):211-6. [PMID: 11931549]
• [15]: M E Sebert et al. (2002) Microarray-based identification of htrA, a Streptococcus pneumoniae gene that is regulated by the CiaRH two-component system and contributes to nasopharyngeal colonization. Infection And Immunity 70(8):4059-67. [PMID: 12117912]
• [16]: Philippe Giammarinaro et al. (1999) Genetic and physiological studies of the CiaH-CiaR two-component signal-transducing system involved in cefotaxime resistance and competence of Streptococcus pneumoniae. Microbiology (Reading, England) 145 ( Pt 8):1859-1869. [PMID: 10463152]