Detailed information NTG0000135

Experimentally validated

Overview

• Name: comC/comC2
• Type: Regulator
• Locus tag: A66_RS00015
• Genome accession: NZ_LN847353
• Coordinates: 2206..2331 (-)
• Length: 41 a.a.
• NCBI ID: WP_000799686.1
• Uniprot ID: P60242
• Organism: Streptococcus pneumoniae A66
• 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: 1..7331

Locus tag	Gene name	Coordinates (strand)	Size (bp)	Protein ID	Product	Description
A66_RS00005 (A66_00001)	comE	111..863 (-)	753	WP_053039410.1	competence system response regulator transcription factor ComE	Regulator
A66_RS00010 (A66_00002)	comD/comD2	860..2185 (-)	1326	WP_000364846.1	competence system sensor histidine kinase ComD	Regulator
A66_RS00015 (A66_00003)	comC/comC2	2206..2331 (-)	126	WP_000799686.1	competence-stimulating peptide ComC	Regulator
A66_RS00025 (A66_00004)	rlmH	2613..3092 (-)	480	WP_000695929.1	23S rRNA (pseudouridine(1915)-N(3))-methyltransferase RlmH	-
A66_RS00030 (A66_00005)	htrA	3275..4456 (+)	1182	WP_000681598.1	S1C family serine protease	Regulator
A66_RS00035 (A66_00006)	spo0J	4514..5272 (+)	759	WP_000410378.1	ParB/RepB/Spo0J family partition protein	Regulator
A66_RS00040 (A66_00007)	dnaA	5485..6846 (+)	1362	WP_000660618.1	chromosomal replication initiator protein DnaA	-

Sequence

Protein

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

>NTDB_id=135 A66_RS00015 WP_000799686.1 2206..2331(-) (comC/comC2) [Streptococcus pneumoniae A66]
MKNTVKLEQFVALKEKDLQKIKGGEMRISRIILDFLFLRKK

Nucleotide

• Length: 126 bp

>NTDB_id=135 A66_RS00015 WP_000799686.1 2206..2331(-) (comC/comC2) [Streptococcus pneumoniae A66]
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 TIGR4	100	100	1
comC/comC1	Streptococcus pneumoniae Rx1	80.488	100	0.805
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	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]