Detailed information NTG0000136

Experimentally validated

Overview

• Name: comC/comC1
• Type: Regulator
• Locus tag: SPD_RS10930
• Genome accession: NC_008533
• Coordinates: 2042838..2042963 (-)
• Length: 41 a.a.
• NCBI ID: WP_000799689.1
• Uniprot ID: P60242
• Organism: Streptococcus pneumoniae D39
• 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: 2037838..2047963

Locus tag	Gene name	Coordinates (strand)	Size (bp)	Protein ID	Product	Description
SPD_RS12055 (SPD_2059)	-	2038176..2039779 (-)	1604	Protein_2017	YhgE/Pip family protein	-
SPD_RS10905 (SPD_2060)	-	2039958..2040500 (+)	543	WP_001158266.1	TetR/AcrR family transcriptional regulator	-
SPD_RS10920 (SPD_2063)	comE	2040743..2041495 (-)	753	WP_000866065.1	competence system response regulator transcription factor ComE	Regulator
SPD_RS10925 (SPD_2064)	comD/comD1	2041492..2042817 (-)	1326	WP_000362880.1	competence system sensor histidine kinase ComD	Regulator
SPD_RS10930 (SPD_2065)	comC/comC1	2042838..2042963 (-)	126	WP_000799689.1	competence-stimulating peptide ComC	Regulator
SPD_RS10940 (SPD_2067)	rlmH	2043245..2043724 (-)	480	WP_000695929.1	23S rRNA (pseudouridine(1915)-N(3))-methyltransferase RlmH	-
SPD_RS10945 (SPD_2068)	htrA	2043907..2045088 (+)	1182	WP_000681597.1	S1C family serine protease	Regulator
SPD_RS10950 (SPD_2069)	spo0J	2045146..2045904 (+)	759	WP_000410378.1	ParB/RepB/Spo0J family partition protein	Regulator

Regulatory network

Positive effect      

Negative effect

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

Sequence

Protein

• Length: 41 a.a.
• Molecular weight: 4971.00 Da
• Isoelectric Point: 11.0775

>NTDB_id=136 SPD_RS10930 WP_000799689.1 2042838..2042963(-) (comC/comC1) [Streptococcus pneumoniae D39]
MKNTVKLEQFVALKEKDLQKIKGGEMRLSKFFRDFILQRKK

Nucleotide

• Length: 126 bp

>NTDB_id=136 SPD_RS10930 WP_000799689.1 2042838..2042963(-) (comC/comC1) [Streptococcus pneumoniae D39]
ATGAAAAACACAGTTAAATTGGAACAGTTTGTAGCTTTGAAGGAAAAAGACTTACAAAAGATTAAAGGTGGGGAGATGAG
GTTGTCAAAATTCTTCCGTGATTTTATTTTACAAAGAAAAAAGTAA

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:

EMRLSKFFRDFILQRKK

Domains

Predicted by InterproScan.

• COMC family (ComC) (1-31)

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/comC1	Streptococcus pneumoniae G54	100	100	1
comC/comC1	Streptococcus pneumoniae Rx1	100	100	1
comC/comC1	Streptococcus pneumoniae R6	100	100	1
comC/comC2	Streptococcus pneumoniae A66	80.488	100	0.805
comC/comC2	Streptococcus pneumoniae TIGR4	80.488	100	0.805
comC	Streptococcus mitis SK321	78.049	100	0.78
comC	Streptococcus mitis NCTC 12261	74.074	67.5	0.5
comC/blpC	Streptococcus mutans UA159	44.444	87.805	0.39

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]