Detailed information NTG0000256

Experimentally validated

Overview

• Name: htrA
• Type: Regulator
• Locus tag: KZH43_RS10270
• Genome accession: NZ_CP079923
• Coordinates: 2027977..2029158 (+)
• Length: 393 a.a.
• NCBI ID: WP_000681597.1
• Uniprot ID: -
• Organism: Streptococcus pneumoniae Rx1
• Function: degrading CSP; selective degradation of ComEA and ComEC Competence regulation

Function

The htrA gene encodes a protease that functions in both general stress response and as an error sensor that specifically represses genetic competence when the overall level of biosynthetic errors in cellular proteins is low. HtrA digests the competence-stimulating peptide (CSP), constituting the primary extracytoplasmic CSP-degrading activity in cultures of S. pneumoniae. This digestion of CSP by HtrA is reduced in the presence of other unfolded proteins that serve as alternative targets for degradation, providing a mechanism by which HtrA monitors the frequency of biosynthetic errors resulting in protein misfolding. HtrA also mediates selective degradation of ComEA and ComEC.

Genomic Context

Location: 2022977..2034158

Locus tag	Gene name	Coordinates (strand)	Size (bp)	Protein ID	Product	Description
KZH43_RS10230 (KZH43_10225)	-	2024028..2024570 (+)	543	WP_001158266.1	TetR/AcrR family transcriptional regulator	-
KZH43_RS10245 (KZH43_10240)	comE	2024813..2025565 (-)	753	WP_000866065.1	competence system response regulator transcription factor ComE	Regulator
KZH43_RS10250 (KZH43_10245)	comD/comD1	2025562..2026887 (-)	1326	WP_000362880.1	competence system sensor histidine kinase ComD	Regulator
KZH43_RS10255 (KZH43_10250)	comC/comC1	2026908..2027033 (-)	126	WP_000799689.1	competence-stimulating peptide ComC	Regulator
KZH43_RS10265 (KZH43_10260)	rlmH	2027315..2027794 (-)	480	WP_000695929.1	23S rRNA (pseudouridine(1915)-N(3))-methyltransferase RlmH	-
KZH43_RS10270 (KZH43_10265)	htrA	2027977..2029158 (+)	1182	WP_000681597.1	S1C family serine protease	Regulator
KZH43_RS10275 (KZH43_10270)	spo0J	2029216..2029974 (+)	759	WP_000410378.1	ParB/RepB/Spo0J family partition protein	Regulator

Regulatory network

Positive effect      

Negative effect

Regulator	Target	Regulation
htrA	comEA/celA/cilE	negative effect
htrA	comC/comC1	negative effect
htrA	comEC/celB	negative effect
ciaR	htrA	positive effect
ciaH	htrA	positive effect
comC/comC1	comD/comD1	positive effect
comD/comD1	comE	positive effect
comE	comD/comD1	positive effect
comB	comC/comC1	positive effect
comE	comB	positive effect
ciaR	comC/comC1	negative effect
ciaH	comC/comC1	negative effect
comA	comC/comC1	positive effect
comE	comA	positive effect
comE	comC/comC1	positive effect
comE	comE	positive effect
comE	comX/comX1	positive effect
comE	comX/comX2	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: 393 a.a.
• Molecular weight: 41841.72 Da
• Isoelectric Point: 6.8902

>NTDB_id=256 KZH43_RS10270 WP_000681597.1 2027977..2029158(+) (htrA) [Streptococcus pneumoniae Rx1]
MKHLKTFYKKWFQLLVVIVISFFSGALGSFSITQLTQKSSVNNSNNNSTITQTAYKNENSTTQAVNKVKDAVVSVITYSA
NRQNSVFGNDDTDTDSQRISSEGSGVIYKKNDKEAYIVTNNHVINGASKVDIRLSDGTKVPGEIVGADTFSDIAVVKISS
EKVTTVAEFGDSSKLTVGETAIAIGSPLGSEYANTVTQGIVSSLNRNVSLKSEDGQAISTKAIQTDTAINPGNSGGPLIN
IQGQVIGITSSKIATNGGTSVEGLGFAIPANDAINIIEQLEKNGKVTRPALGIQMVNLSNVSTSDIRRLNIPSNVTSGVI
VRSVQSNMPANGHLEKYDVITKVDDKEIASSTDLQSALYNHSIGDTIKITYYRNGKEETTSIKLNKSSGDLES

Nucleotide

• Length: 1182 bp

>NTDB_id=256 KZH43_RS10270 WP_000681597.1 2027977..2029158(+) (htrA) [Streptococcus pneumoniae Rx1]
ATGAAACATCTAAAAACATTTTACAAAAAATGGTTTCAATTATTAGTCGTTATCGTCATTAGCTTTTTTAGTGGAGCCTT
GGGTAGTTTTTCAATAACTCAACTAACTCAAAAAAGTAGTGTAAACAACTCTAACAACAATAGTACTATTACACAAACTG
CCTATAAGAACGAAAATTCAACAACACAGGCTGTTAACAAAGTAAAAGATGCTGTTGTTTCTGTTATTACTTATTCGGCA
AACAGACAAAATAGCGTATTTGGCAATGATGATACTGACACAGATTCTCAGCGAATCTCTAGTGAAGGATCTGGAGTTAT
TTATAAAAAGAATGATAAAGAAGCTTACATCGTCACCAACAATCACGTTATAAATGGCGCCAGCAAAGTAGATATTCGAT
TGTCAGATGGGACTAAAGTACCTGGAGAAATTGTCGGAGCTGACACTTTCTCTGATATTGCTGTCGTCAAAATCTCTTCA
GAAAAAGTGACAACAGTAGCTGAGTTTGGTGATTCTAGTAAGTTAACTGTAGGAGAAACTGCTATTGCCATCGGTAGCCC
GTTAGGTTCTGAATATGCAAATACTGTCACTCAAGGTATCGTATCCAGTCTCAATAGAAATGTATCCTTAAAATCGGAAG
ATGGACAAGCTATTTCTACAAAAGCCATCCAAACTGATACTGCTATTAACCCAGGTAACTCTGGCGGCCCACTGATCAAT
ATTCAAGGGCAGGTTATCGGAATTACCTCAAGTAAAATTGCTACAAATGGAGGAACATCTGTAGAAGGTCTTGGTTTCGC
AATTCCTGCAAATGATGCTATCAATATTATTGAACAGTTAGAAAAAAACGGAAAAGTGACGCGTCCAGCTTTGGGAATCC
AGATGGTTAATTTATCTAATGTGAGTACAAGCGACATCAGAAGACTCAATATTCCAAGTAATGTTACATCTGGTGTAATT
GTTCGTTCGGTACAAAGTAATATGCCTGCCAATGGTCACCTTGAAAAATACGATGTAATTACAAAAGTAGATGACAAAGA
GATTGCTTCATCAACAGACTTACAAAGTGCTCTTTACAACCATTCTATCGGAGACACCATTAAGATAACCTACTATCGTA
ACGGGAAAGAAGAAACTACCTCTATCAAACTTAACAAGAGTTCAGGTGATTTAGAATCTTAA

Domains

Predicted by InterproScan.

• Trypsin-like peptidase domain (Trypsin_2) (103-248)

• PDZ domain (PDZ_2) (289-384)

Similar proteins

Only experimentally validated proteins are listed.

Protein	Organism	Identities (%)	Coverage (%)	Ha-value
htrA	Streptococcus pneumoniae D39	100	100	1
htrA	Streptococcus pneumoniae R6	100	100	1
htrA	Streptococcus pneumoniae TIGR4	100	100	1
htrA	Streptococcus mitis NCTC 12261	97.201	100	0.972
htrA	Streptococcus gordonii str. Challis substr. CH1	66.414	100	0.669
htrA	Streptococcus mutans UA159	54.569	100	0.547

References

• [1]: Jada L George et al. (2024) Streptococcus pneumoniae secretion chaperones PrsA, SlrA, and HtrA are required for competence, antibiotic resistance, colonization, and invasive disease. Infection And Immunity 92(2):e0049023. [PMID: 38226817]
• [2]: 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]
• [3]: Mickaël Maziero et al. (2023) Fever-like temperature bursts promote competence development via an HtrA-dependent pathway in Streptococcus pneumoniae. PLoS Genetics 19(9):e1010946. [PMID: 37699047]
• [4]: Katharina Peters et al. (2021) New Insights into Beta-Lactam Resistance of Streptococcus pneumoniae: Serine Protease HtrA Degrades Altered Penicillin-Binding Protein 2x. Microorganisms 9(8):1685. [PMID: 34442764]
• [5]: Yanni Liu et al. (2019) HtrA-mediated selective degradation of DNA uptake apparatus accelerates termination of pneumococcal transformation. Molecular Microbiology 112(4):1308-1325. [PMID: 31396996]
• [6]: Travis J Kochan et al. (2013) The HtrA protease of Streptococcus pneumoniae controls density-dependent stimulation of the bacteriocin blp locus via disruption of pheromone secretion. Journal of Bacteriology 195(7):1561-72. [PMID: 23354751]
• [7]: Sacha F de Stoppelaar et al. (2013) Streptococcus pneumoniae serine protease HtrA, but not SFP or PrtA, is a major virulence factor in pneumonia. PloS One 8(11):e80062. [PMID: 24244609]
• [8]: 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]
• [9]: Kai Fan et al. (2011) Solution structure of HtrA PDZ domain from Streptococcus pneumoniae and its interaction with YYF-COOH containing peptides. Journal of Structural Biology 176(1):16-23. [PMID: 21757011]
• [10]: Kathleen E Stevens et al. (2011) Competence in Streptococcus pneumoniae is regulated by the rate of ribosomal decoding errors. MBio 2(5):e00071-11. [PMID: 21933920]
• [11]: Ho-Ching Tiffany Tsui et al. (2011) Dynamic distribution of the SecA and SecY translocase subunits and septal localization of the HtrA surface chaperone/protease during Streptococcus pneumoniae D39 cell division. MBio 2(5):e00202-11. [PMID: 21990615]
• [12]: Kai Fan et al. (2010) 1H, 13C and 15N resonance assignment of the PDZ domain of HtrA from Streptococcus pneumoniae. Biomolecular NMR Assignments 4(1):79-82. [PMID: 20437142]
• [13]: Suzanne Dawid et al. (2009) Bacteriocin activity of Streptococcus pneumoniae is controlled by the serine protease HtrA via posttranscriptional regulation. Journal of Bacteriology 191(5):1509-18. [PMID: 19103930]
• [14]: 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]
• [15]: Yasser Musa Ibrahim et al. (2004) Role of HtrA in the virulence and competence of Streptococcus pneumoniae. Infection And Immunity 72(6):3584-91. [PMID: 15155668]
• [16]: 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]
• [17]: 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]