Gene Rv0410c
in Mycobacterium tuberculosis H37Rv
General annotation
| Type | CDS |
| Function | Involved in signal transduction (via phosphorylation). Thought to regulate amino-acid uptake and stationary-phase metabolism. Phosphorylates the peptide substrate myelin basic protein (MBP) at serine residues [catalytic activity: ATP + a protein = ADP + a phosphoprotein]. |
| Product | Serine/threonine-protein kinase PknG (protein kinase G) (STPK G) |
| Comments | Rv0410c, (MTCY22G10.06c), len: 750 aa. PknG, serine/threonine-protein kinase (see citations below), equivalent to PKNG_MYCLE|P57993|13092623|CAC29812.1|AL583918 probable serine/threonine-protein kinase from Mycobacterium leprae (767 aa). Also similar to others e.g. AB76890.1|AL159139 putative serine/threonine protein kinase from Streptomyces coelicolor (774 aa); etc. Contains PS00108 Serine/Threonine protein kinases active-site signature. Contains Hank's kinase subdomain. Belongs to the Ser/Thr family of protein kinases. Structure of PknG with inhibitor AX20017 reveals that the inhibitor-binding pocket is shaped by a unique set of amino acid side chains not found in any human kinase (See Scherr et al., 2007). |
| Functional category | Regulatory proteins |
| Proteomics | Identified in the cell membrane fraction of M. tuberculosis H37Rv using 2DLC/MS (See Mawuenyega et al., 2005). 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 membrane protein fraction and whole cell lysates of M. tuberculosis H37Rv but not the culture filtrate (See de Souza et al., 2011). |
| Mutant | Essential gene for in vitro growth of H37Rv in a MtbYM rich medium, by Himar1 transposon mutagenesis (see Minato et al. 2019). Non-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 for in vitro growth of H37Rv, by Himar1 transposon mutagenesis (See Griffin et al., 2011). M. bovis BCG pknG|Rv0410c mutant is transferred to lysosomes during macrophage infection while wild-type is not (See Walburger et al., 2004). M. tuberculosis H37Rv pknG|Rv0410c mutant grows slower than wild-type, in vitro; accumulates glutamate and glutamine; is not attenuated in CD-1 mice (See Cowley et al., 2004). M. tuberculosis H37Rv pknG|Rv0410c mutant shows increased sensitivity to erythromycin and sulfachloropyridazine (See Wolff et al., 2009). Check for mutants available at TARGET website |
Coordinates
| Type | Start | End | Orientation |
|---|---|---|---|
| CDS | 495062 | 497314 | - |
Genomic sequence
Feature type
Upstream flanking region (bp)
Downstream flanking region (bp)
Update
Protein sequence
>Mycobacterium tuberculosis H37Rv|Rv0410c|pknG
MAKASETERSGPGTQPADAQTATSATVRPLSTQAVFRPDFGDEDNFPHPTLGPDTEPQDRMATTSRVRPPVRRLGGGLVEIPRAPDIDPLEALMTNPVVPESKRFCWNCGRPVGRSDSETKGASEGWCPYCGSPYSFLPQLNPGDIVAGQYEVKGCIAHGGLGWIYLALDRNVNGRPVVLKGLVHSGDAEAQAMAMAERQFLAEVVHPSIVQIFNFVEHTDRHGDPVGYIVMEYVGGQSLKRSKGQKLPVAEAIAYLLEILPALSYLHSIGLVYNDLKPENIMLTEEQLKLIDLGAVSRINSFGYLYGTPGFQAPEIVRTGPTVATDIYTVGRTLAALTLDLPTRNGRYVDGLPEDDPVLKTYDSYGRLLRRAIDPDPRQRFTTAEEMSAQLTGVLREVVAQDTGVPRPGLSTIFSPSRSTFGVDLLVAHTDVYLDGQVHAEKLTANEIVTALSVPLVDPTDVAASVLQATVLSQPVQTLDSLRAARHGALDADGVDFSESVELPLMEVRALLDLGDVAKATRKLDDLAERVGWRWRLVWYRAVAELLTGDYDSATKHFTEVLDTFPGELAPKLALAATAELAGNTDEHKFYQTVWSTNDGVISAAFGLARARSAEGDRVGAVRTLDEVPPTSRHFTTARLTSAVTLLSGRSTSEVTEEQIRDAARRVEALPPTEPRVLQIRALVLGGALDWLKDNKASTNHILGFPFTSHGLRLGVEASLRSLARVAPTQRHRYTLVDMANKVRPTSTF
Bibliography
- Av-Gay Y et al. [2000]. The eukaryotic-like Ser/Thr protein kinases of Mycobacterium tuberculosis. Review
- Koul A et al. [2001]. Serine/threonine protein kinases PknF and PknG of Mycobacterium tuberculosis: characterization and localization. Product Biochemistry
- Sassetti CM et al. [2003]. Genes required for mycobacterial growth defined by high density mutagenesis. Mutant
- Cowley S, Ko M, Pick N, Chow R, Downing KJ, Gordhan BG, Betts JC, Mizrahi V, Smith DA, Stokes RW and Av-Gay Y [2004]. The Mycobacterium tuberculosis protein serine/threonine kinase PknG is linked to cellular glutamate/glutamine levels and is important for growth in vivo. Mutant
- Walburger A et al. [2004]. Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Mutant
- Mawuenyega KG et al. [2005]. Mycobacterium tuberculosis functional network analysis by global subcellular protein profiling. Proteomics
- Scherr N, Honnappa S, Kunz G, Mueller P, Jayachandran R, Winkler F, Pieters J and Steinmetz MO [2007]. Structural basis for the specific inhibition of protein kinase G, a virulence factor of Mycobacterium tuberculosis. Structure
- Székely R et al. [2008]. A novel drug discovery concept for tuberculosis: inhibition of bacterial and host cell signalling. Biochemistry
- O'Hare HM et al. [2008]. Regulation of glutamate metabolism by protein kinases in mycobacteria. Biochemistry
- Tiwari D et al. [2009]. Key residues in Mycobacterium tuberculosis protein kinase G play a role in regulating kinase activity and survival in the host. Biochemistry Mutant
- Wolff KA, Nguyen HT, Cartabuke RH, Singh A, Ogwang S and Nguyen L [2009]. Protein kinase G is required for intrinsic antibiotic resistance 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
- 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
