Gene Rv0014c
in Mycobacterium tuberculosis H37Rv
General annotation
| Type | CDS |
| Function | Involved in signal transduction (via phosphorylation). Thought to regulate cell division/differentiation. Can phosphorylate the peptide substrate myelin basic protein (MBP) [catalytic activity: ATP + a protein = ADP + a phosphoprotein]. |
| Product | Transmembrane serine/threonine-protein kinase B PknB (protein kinase B) (STPK B) |
| Comments | Rv0014c, (MTCY10H4.14c), len: 626 aa. PknB, transmembrane serine/threonine-protein kinase (see citations below). Contains PS00107 Protein kinases ATP-binding region signature, and PS00108 Serine/Threonine protein kinases active-site signature. Contains Hank's kinase subdomain. Belongs to the Ser/Thr family of protein kinases. Experimental studies show evidence of auto-phosphorylation on serine/threonine residues. PknB has been shown to be a substrate for PstP and its kinase activity is affected by PstP-mediated dephosphorylation. PknB and PstP (Rv0018c) may act as a functional pair in vivo to control mycobacterial cell growth. |
| Functional category | Regulatory proteins |
| Proteomics | Identified by mass spectrometry in Triton X-114 extracts of M. tuberculosis H37Rv (See Malen et al., 2010). Identified by mass spectrometry in M. tuberculosis H37Rv-infected guinea pig lungs at 90 days but not 30 days (See Kruh et al., 2010). Identified by mass spectrometry in the culture filtrate, membrane protein fraction, and whole cell lysates of M. tuberculosis H37Rv (See de Souza et al., 2011). Translational start site supported by proteomics data (See Kelkar et al., 2011). |
| Transcriptomics | mRNA identified by microarray analysis and down-regulated after 4h, 24h and 96h of starvation (see Betts et al., 2002). |
| Mutant | Essential gene for in vitro growth of H37Rv in a MtbYM rich medium, by Himar1 transposon mutagenesis (see Minato et al. 2019). Essential gene for in vitro growth of H37Rv, by analysis of saturated Himar1 transposon libraries (see DeJesus et al. 2017). Essential gene by Himar1 transposon mutagenesis in H37Rv strain (see Sassetti et al., 2003). Essential gene, shown with M. tuberculosis H37Rv pknB|Rv0014c conditional mutant (See Forti et al., 2009). Essential gene for in vitro growth of H37Rv, by Himar1 transposon mutagenesis (See Griffin et al., 2011). Check for mutants available at TARGET website |
Coordinates
| Type | Start | End | Orientation |
|---|---|---|---|
| CDS | 15590 | 17470 | - |
Genomic sequence
Feature type
Upstream flanking region (bp)
Downstream flanking region (bp)
Update
Protein sequence
>Mycobacterium tuberculosis H37Rv|Rv0014c|pknB
MTTPSHLSDRYELGEILGFGGMSEVHLARDLRLHRDVAVKVLRADLARDPSFYLRFRREAQNAAALNHPAIVAVYDTGEAETPAGPLPYIVMEYVDGVTLRDIVHTEGPMTPKRAIEVIADACQALNFSHQNGIIHRDVKPANIMISATNAVKVMDFGIARAIADSGNSVTQTAAVIGTAQYLSPEQARGDSVDARSDVYSLGCVLYEVLTGEPPFTGDSPVSVAYQHVREDPIPPSARHEGLSADLDAVVLKALAKNPENRYQTAAEMRADLVRVHNGEPPEAPKVLTDAERTSLLSSAAGNLSGPRTDPLPRQDLDDTDRDRSIGSVGRWVAVVAVLAVLTVVVTIAINTFGGITRDVQVPDVRGQSSADAIATLQNRGFKIRTLQKPDSTIPPDHVIGTDPAANTSVSAGDEITVNVSTGPEQREIPDVSTLTYAEAVKKLTAAGFGRFKQANSPSTPELVGKVIGTNPPANQTSAITNVVIIIVGSGPATKDIPDVAGQTVDVAQKNLNVYGFTKFSQASVDSPRPAGEVTGTNPPAGTTVPVDSVIELQVSKGNQFVMPDLSGMFWVDAEPRLRALGWTGMLDKGADVDAGGSQHNRVVYQNPPAGTGVNRDGIITLRFGQ
Bibliography
- Av-Gay Y, Jamil S and Drews SJ [1999]. Expression and characterization of the Mycobacterium tuberculosis serine/threonine protein kinase PknB. Product Sequence
- Av-Gay Y et al. [2000]. The eukaryotic-like Ser/Thr protein kinases of Mycobacterium tuberculosis. Review
- Drews SJ et al. [2001]. A protein kinase inhibitor as an antimycobacterial agent. Product Biochemistry
- Betts JC et al. [2002]. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Transcriptome
- Young TA, Delagoutte B, Endrizzi JA, Falick AM and Alber T [2003]. Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases. Structure
- Sassetti CM et al. [2003]. Genes required for mycobacterial growth defined by high density mutagenesis. Mutant
- Boitel B, Ortiz-Lombardia M, Duran R, Pompeo F, Cole ST, Cervenansky C and Alzari PM [2003]. PknB kinase activity is regulated by phosphorylation in two Thr residues and dephosphorylation by PstP, the cognate phospho-Ser/Thr phosphatase, in Mycobacterium tuberculosis. Product Biochemistry Mutant Function
- Ortiz-Lombardía M et al. [2003]. Crystal structure of the catalytic domain of the PknB serine/threonine kinase from Mycobacterium tuberculosis. Structure
- Wehenkel A, Fernandez P, Bellinzoni M, Catherinot V, Barilone N, Labesse G, Jackson M and Alzari PM [2006]. The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria. Structure
- Székely R et al. [2008]. A novel drug discovery concept for tuberculosis: inhibition of bacterial and host cell signalling. Biochemistry
- Forti F et al. [2009]. Pristinamycin-inducible gene regulation in mycobacteria. Mutant
- Målen H et al. [2010]. Definition of novel cell envelope associated proteins in Triton X-114 extracts of Mycobacterium tuberculosis H37Rv. Proteomics
- Kruh NA et al. [2010]. Portrait of a pathogen: the Mycobacterium tuberculosis proteome in vivo. Proteomics
- de Souza GA et al. [2011]. Bacterial proteins with cleaved or uncleaved signal peptides of the general secretory pathway. Proteomics
- Kelkar DS et al. [2011]. Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry. Proteomics Sequence
- Griffin JE et al. [2011]. High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. Mutant
- DeJesus MA et al. [2017]. Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis. Mutant
- Minato Y et al. [2019]. Genomewide Assessment of Mycobacterium tuberculosis Conditionally Essential Metabolic Pathways. Mutant
