Detailed information NTG0000133

Experimentally validated

Overview

• Name: comC/comC2
• Type: Regulator
• Locus tag: SP_RS11435
• Genome accession: NC_003028
• Coordinates: 2157760..2157885 (-)
• Length: 41 a.a.
• NCBI ID: WP_000799686.1
• Uniprot ID: P60242
• Organism: Streptococcus pneumoniae TIGR4
• Function: binding to ComD; induce autophosphorylation of ComD Competence regulation

Function

The comC gene encodes the precursor of the competence-stimulating peptide (CSP), which is processed and secreted by the ComAB transporter. CSP accumulates in the extracellular environment and binds to the histidine kinase ComD, triggering a signaling cascade that activates the expression of competence genes. This process is essential for the induction of the competent state, enabling the bacterium to perform natural transformation. Two major allelic variants of the comC gene have been identified in S. pneumoniae: comC1 and comC2. These variants result in the production of two distinct CSPs, CSP1 and CSP2. Each CSP variant identifies a specific pherotype, and strains carrying one variant are typically unable to respond to the other CSP variant due to receptor specificity.

Genomic Context

Location: 2152760..2162885

Locus tag	Gene name	Coordinates (strand)	Size (bp)	Protein ID	Product	Description
SP_RS13565	-	2153099..2154701 (-)	1603	Protein_2131	YhgE/Pip family protein	-
SP_RS11410 (SP_2234)	-	2154880..2155422 (+)	543	WP_001158266.1	TetR/AcrR family transcriptional regulator	-
SP_RS11425 (SP_2235)	comE	2155665..2156417 (-)	753	WP_000866065.1	competence system response regulator transcription factor ComE	Regulator
SP_RS11430 (SP_2236)	comD/comD2	2156414..2157739 (-)	1326	WP_000364845.1	competence system sensor histidine kinase ComD	Regulator
SP_RS11435 (SP_2237)	comC/comC2	2157760..2157885 (-)	126	WP_000799686.1	competence-stimulating peptide ComC	Regulator
SP_RS11445 (SP_2238)	rlmH	2158167..2158646 (-)	480	WP_000695929.1	23S rRNA (pseudouridine(1915)-N(3))-methyltransferase RlmH	-
SP_RS11450 (SP_2239)	htrA	2158829..2160010 (+)	1182	WP_000681597.1	S1C family serine protease	Regulator
SP_RS11455 (SP_2240)	spo0J	2160068..2160826 (+)	759	WP_000410378.1	ParB/RepB/Spo0J family partition protein	Regulator

Regulatory network

Positive effect      

Negative effect

Regulator	Target	Regulation
comC/comC2	comD/comD2	positive effect
comD/comD2	comE	positive effect
comE	comE	positive effect
comE	comX/comX1	positive effect
comE	comW	positive effect
comE	comA	positive effect
comE	comB	positive effect
comE	comM	positive effect
comE	comX/comX2	positive effect
comE	comD/comD2	positive effect
comE	comC/comC2	positive effect
stkP	comE	positive effect
comX/comX1	late competence genes	positive effect
clpP	comX/comX1	negative effect
comW	comX/comX1	positive effect
clpE	comX/comX1	negative effect
comW	comX/comX2	positive effect
clpP	comW	negative effect
mecA	comW	negative effect
clpC	comW	negative effect
comA	comC/comC2	positive effect
comB	comC/comC2	positive effect
comM	cbpD	negative effect
comX/comX2	late competence genes	positive effect
clpP	comX/comX2	negative effect
clpE	comX/comX2	negative effect
ciaH	comC/comC2	negative effect
htrA	comC/comC2	negative effect
ciaR	comC/comC2	negative effect
comX/comX2	late competence genes	positive effect
comX/comX1	late competence genes	positive effect
cbpD	lytA	positive effect
cbpD	lytC	positive effect
ciaH	htrA	positive effect
htrA	comEC/celB	negative effect
htrA	comEA/celA/cilE	negative effect
ciaR	htrA	positive effect

Sequence

Protein

• Length: 41 a.a.
• Molecular weight: 4907.00 Da
• Isoelectric Point: 11.0006

>NTDB_id=133 SP_RS11435 WP_000799686.1 2157760..2157885(-) (comC/comC2) [Streptococcus pneumoniae TIGR4]
MKNTVKLEQFVALKEKDLQKIKGGEMRISRIILDFLFLRKK

Nucleotide

• Length: 126 bp

>NTDB_id=133 SP_RS11435 WP_000799686.1 2157760..2157885(-) (comC/comC2) [Streptococcus pneumoniae TIGR4]
ATGAAAAACACAGTTAAATTGGAACAGTTTGTAGCTTTGAAGGAAAAAGACTTACAAAAGATTAAAGGTGGGGAGATGAG
GATTTCAAGAATCATCCTTGATTTTCTTTTCCTACGAAAAAAGTAA

CSP

This gene is known to encode the precursor of competence stimulating peptide (CSP), which involves in competence development. The mature CSP sequence is displayed as below:

EMRISRIILDFLFLRKK

Domains

Predicted by InterproScan.

• COMC family (ComC) (1-29)

3D structure

• PDB: 6CJ8
• PDB: 6COO
• PDB: 6COP
• PDB: 6COQ
• PDB: 6COR
• PDB: 6COS
• PDB: 6COW
• PDB: 6OBW
• PDB: 6OC2
• PDB: 6OC4
• PDB: 6OLD
• PDB: 6V1N

Similar proteins

Only experimentally validated proteins are listed.

Protein	Organism	Identities (%)	Coverage (%)	Ha-value
comC/comC2	Streptococcus pneumoniae A66	100	100	1
comC/comC1	Streptococcus pneumoniae R6	80.488	100	0.805
comC/comC1	Streptococcus pneumoniae G54	80.488	100	0.805
comC/comC1	Streptococcus pneumoniae D39	80.488	100	0.805
comC/comC1	Streptococcus pneumoniae Rx1	80.488	100	0.805
comC	Streptococcus mitis SK321	75.61	100	0.756
comC	Streptococcus mitis NCTC 12261	57.5	100	0.575

References

• [1]: Tahmina A Milly et al. (2021) Harnessing Multiple, Nonproteogenic Substitutions to Optimize CSP:ComD Hydrophobic Interactions in Group 1 Streptococcus pneumoniae. Chembiochem : A European Journal of Chemical Biology 22(11):1940-1947. [PMID: 33644965]
• [2]: Yifang Yang et al. (2019) Exploring the competence stimulating peptide (CSP) N-terminal requirements for effective ComD receptor activation in group1 Streptococcus pneumoniae. Bioorganic Chemistry 89:102987. [PMID: 31132605]
• [3]: Bimal Koirala et al. (2019) Unveiling the Importance of Amide Protons in CSP:ComD Interactions in Streptococcus pneumoniae. ACS Medicinal Chemistry Letters 10(6):880-886. [PMID: 31223442]
• [4]: Bimal Koirala et al. (2018) Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae. Beilstein Journal of Organic Chemistry 14:1769-1777. [PMID: 30112082]
• [5]: Yifang Yang et al. (2017) Structure-Activity Relationships of the Competence Stimulating Peptides (CSPs) in Streptococcus pneumoniae Reveal Motifs Critical for Intra-group and Cross-group ComD Receptor Activation. ACS Chemical Biology 12(4):1141-1151. [PMID: 28221753]
• [6]: M Ramirez et al. (1997) Ubiquitous distribution of the competence related genes comA and comC among isolates of Streptococcus pneumoniae. Microbial Drug Resistance (Larchmont, N.Y.) 3(1):39-52. [PMID: 9109095]
• [7]: G Pozzi et al. (1996) Competence for genetic transformation in encapsulated strains of Streptococcus pneumoniae: two allelic variants of the peptide pheromone. Journal of Bacteriology 178(20):6087-90. [PMID: 8830714]
• [8]: L S Håvarstein et al. (1996) Identification of the streptococcal competence-pheromone receptor. Molecular Microbiology 21(4):863-9. [PMID: 8878047]