Gene - combatTB X

devR

Type: protein_coding
Name: devR
Locus Name: Rv3133c
Product: Two component transcriptional regulatory protein DevR (probably LuxR/UhpA-family)
Functional Category: Regulatory proteins
Location: 3499262..3499915 (- strand)
Gene Length: 653 bp
Nucleotides: GTGGTAAAGGTCTTCTTGGTCGATGACCACGAGGTGGTGCGTCGTGGTCTGGTTGACTTGCTTGGGGCCGATCCCGAGCTTGACGTCGTAGGTGAGGCGGGTTCGGTCGCCGAGGCGATGGCCAGGGTTCCTGCCGCGCGCCCAGATGTCGCGGTGCTGGATGTCCGGTTGCCCGATGGCAACGGCATTGAACTGTGCCGCGATCTGTTGTCCCGCATGCCCGATCTGCGCTGTCTGATCCTCACGTCCTACACCTCTGACGAGGCCATGCTAGATGCGATTCTCGCCGGTGCCAGCGGATATGTCGTCAAAGACATCAAGGGAATGGAGTTGGCGCGCGCCGTCAAAGATGTGGGCGCTGGACGGTCGCTGCTGGACAATCGGGCCGCGGCCGCGCTGATGGCCAAGCTGCGCGGTGCCGCCGAGAAGCAGGACCCGCTATCAGGCCTTACCGACCAGGAGCGGACGCTACTGGGCCTGCTTAGCGAGGGCCTGACCAACAAGCAGATCGCCGACCGAATGTTCCTAGCCGAAAAGACGGTGAAGAACTACGTGTCGCGGTTGCTGGCCAAGCTGGGCATGGAACGTCGGACGCAAGCCGCGGTATTCGCGACGGAGTTGAAGCGCTCGCGGCCACCCGGTGATGGACCATG
Drug Resistance: Check for drug resistance association at TBDREAMDB
Mutations: Check for mutants available at TARGET

Function

Member of the two-component regulatory system DevR/DevS (also called DosR/DosS) involved in onset of the dormancy response (PubMed:15033981). Regulates an approximately 48-member regulon (PubMed:12953092, PubMed:11416222, PubMed:15033981, PubMed:18400743). When phosphorylated binds and activates the promoter of DevR regulon genes in response to hypoxia (PubMed:18359816, PubMed:21764934, PubMed:28977726). The presence of target DNA increases stability of phospho-DevR in vitro (PubMed:28977726). Activates its own transcription under hypoxic but not aerobic conditions, probably binds as a dimer to tandem binding sites within the devR and hspX promoters (PubMed:18359816). Accepts a phosphate group from DevS (DosS) and from DosT (PubMed:15033981, PubMed:15073296, PubMed:21764934, PubMed:28977726). Does not regulate transcription of dosT (PubMed:19487478). {ECO:0000269|PubMed:11416222, ECO:0000269|PubMed:12953092, ECO:0000269|PubMed:15033981, ECO:0000269|PubMed:15073296, ECO:0000269|PubMed:18359816, ECO:0000269|PubMed:18400743, ECO:0000269|PubMed:19487478, ECO:0000269|PubMed:21764934, ECO:0000269|PubMed:28977726}.

Family

Unknown

GO

host cell cytoplasmic vesicle GO:0044161 cellular_component
dormancy process GO:0022611 biological_process
pathogenesis GO:0009405 biological_process
DNA-binding transcription factor activity GO:0003700 molecular_function
cell wall GO:0005618 cellular_component
extracellular space GO:0005615 cellular_component
cytosol GO:0005829 cellular_component
host cell endosome lumen GO:0072493 cellular_component
DNA binding GO:0003677 molecular_function
positive regulation of transcription, DNA-templated GO:0045893 biological_process
plasma membrane GO:0005886 cellular_component
response to hypoxia GO:0001666 biological_process
phosphorelay signal transduction system GO:0000160 biological_process

InterPro

UniProt: P9WMF9
GenBank: Rv3133c
EnsemblBacteria: Rv3133c
Mycobrowser: Rv3133c

Summary

Name: DNA-binding transcriptional activator DevR/DosR
Family: Unknown
Protein Sequence: MVKVFLVDDHEVVRRGLVDLLGADPELDVVGEAGSVAEAMARVPAARPDVAVLDVRLPDGNGIELCRDLLSRMPDLRCLILTSYTSDEAMLDAILAGASGYVVKDIKGMELARAVKDVGAGRSLLDNRAAAALMAKLRGAAEKQDPLSGLTDQERTLLGLLSEGLTNKQIADRMFLAEKTVKNYVSRLLAKLGMERRTQAAVFATELKRSRPPGDGP
Mass: 23,294 Da
Length: 217 Aa

Rv3133c doesn't seem to be a targeted by any drug.

Two-component system mtu02020
mtu02020
Environmental Information Processing; Signal transduction

Crystal structures of the response regulator DosR from Mycobacterium tuberculosis suggest a helix rearrangement mechanism for phosphorylation activation.: J Mol Biol. 2008 Apr 18;378(1):227-42. doi: 10.1016/j.jmb.2008.02.029. Epub 2008 Feb 26.
Structures of Mycobacterium tuberculosis DosR and DosR-DNA complex involved in gene activation during adaptation to hypoxic latency.: J Mol Biol. 2005 Dec 2;354(3):630-41. doi: 10.1016/j.jmb.2005.09.048. Epub 2005 Oct 3.
The DosS-DosT/DosR Mycobacterial Sensor System.: Biosensors (Basel). 2013;3(3):259-282. doi: 10.3390/bios3030259.
Target DNA stabilizes Mycobacterium tuberculosis DevR/DosR phosphorylation by the full-length oxygen sensors DevS/DosS and DosT.: FEBS J. 2017 Nov;284(22):3954-3967. doi: 10.1111/febs.14284. Epub 2017 Oct 19.
Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry.: Mol Cell Proteomics. 2011 Dec;10(12):M111.011627. doi: 10.1074/mcp.M111.011445. Epub 2011 Oct 3.
The residue threonine 82 of DevR (DosR) is essential for DevR activation and function in Mycobacterium tuberculosis despite its atypical location.: J Bacteriol. 2011 Sep;193(18):4849-58. doi: 10.1128/JB.05051-11. Epub 2011 Jul 15.
Convergence of Ser/Thr and two-component signaling to coordinate expression of the dormancy regulon in Mycobacterium tuberculosis.: J Biol Chem. 2010 Sep 17;285(38):29239-46. doi: 10.1074/jbc.M110.132894. Epub 2010 Jul 14.
Unique roles of DosT and DosS in DosR regulon induction and Mycobacterium tuberculosis dormancy.: Infect Immun. 2009 Aug;77(8):3258-63. doi: 10.1128/IAI.01449-08. Epub 2009 Jun 1.
Role of the dosR-dosS two-component regulatory system in Mycobacterium tuberculosis virulence in three animal models.: Infect Immun. 2009 Mar;77(3):1230-7. doi: 10.1128/IAI.01117-08. Epub 2008 Dec 22.
Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium tuberculosis dormancy regulon.: J Biol Chem. 2008 Jun 27;283(26):18032-9. doi: 10.1074/jbc.M802274200. Epub 2008 Apr 9.
Cooperative binding of phosphorylated DevR to upstream sites is necessary and sufficient for activation of the Rv3134c-devRS operon in Mycobacterium tuberculosis: implication in the induction of DevR target genes.: J Bacteriol. 2008 Jun;190(12):4301-12. doi: 10.1128/JB.01308-07. Epub 2008 Mar 21.
Mycobacterium tuberculosis senses host-derived carbon monoxide during macrophage infection.: Cell Host Microbe. 2008 May 15;3(5):323-30. doi: 10.1016/j.chom.2008.03.007.
Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor.: Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11568-73. doi: 10.1073/pnas.0705054104. Epub 2007 Jul 3.
DevR-DevS is a bona fide two-component system of Mycobacterium tuberculosis that is hypoxia-responsive in the absence of the DNA-binding domain of DevR.: Microbiology. 2004 Apr;150(Pt 4):865-75. doi: 10.1099/mic.0.26218-0.
Two sensor kinases contribute to the hypoxic response of Mycobacterium tuberculosis.: J Biol Chem. 2004 May 28;279(22):23082-7. doi: 10.1074/jbc.M401230200. Epub 2004 Mar 19.
Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis.: Mol Microbiol. 2003 May;48(3):833-43.
Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program.: J Exp Med. 2003 Sep 1;198(5):705-13. doi: 10.1084/jem.20030205.
Deletion of two-component regulatory systems increases the virulence of Mycobacterium tuberculosis.: Infect Immun. 2003 Mar;71(3):1134-40. doi: 10.1128/iai.71.3.1134-1140.2003.
Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding alpha -crystallin.: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7534-9. doi: 10.1073/pnas.121172498.
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.: Nature. 1998 Jun 11;393(6685):537-44. doi: 10.1038/31159.
Characterization of a two-component system, devR-devS, of Mycobacterium tuberculosis.: Tuber Lung Dis. 2000;80(3):141-59. doi: 10.1054/tuld.2000.0240.