Gene - combatTB X

dosT

Type: protein_coding
Name: dosT
Locus Name: Rv2027c
Product: Two component sensor histidine kinase DosT
Functional Category: Regulatory proteins
Location: 2272787..2274508 (- strand)
Gene Length: 1721 bp
Nucleotides: GTGACACACCCTGACAGGGCGAACGTTAACCCTGGCAGCCCGCCATTGCGCGAGACACTGTCGCAGCTTCGGTTGCGAGAGCTGCTGCTGGAAGTCCAAGACCGGATTGAACAGATCGTCGAAGGCCGCGACCGGCTGGATGGTCTGATCGACGCCATCTTGGCGATCACATCGGGACTCAAGCTCGACGCCACCCTGCGCGCCATTGTGCATACCGCCGCCGAGTTGGTGGATGCCCGCTACGGGGCGCTCGGGGTGCGCGGTTACGACCATAGATTGGTCGAATTCGTCTACGAGGGGATCGACGAAGAGACCCGGCACCTCATCGGCTCATTGCCGGAGGGGCGAGGTGTTCTCGGCGCGCTGATCGAGGAGCCAAAGCCGATCCGGCTGGACGATATCTCGCGGCATCCCGCATCGGTTGGATTTCCGCTGCACCATCCGCCGATGCGGACCTTCCTCGGGGTTCCAGTGCGCATCCGCGACGAGGTGTTCGGCAATCTTTACTTGACCGAGAAGGCAGATGGCCAGCCGTTCAGCGATGACGACGAGGTGCTGGTGCAGGCGCTGGCCGCCGCGGCCGGGATTGCCGTTGACAATGCCCGTCTCTTCGAGGAATCACGGACCCGGGAAGCGTGGATCGAGGCAACCCGCGACATCGGAACGCAGATGCTGGCCGGTGCGGACCCGGCCATGGTGTTTCGGCTCATCGCCGAGGAAGCGTTGACGTTGATGGCTGGGGCAGCCACCTTGGTGGCGGTGCCGCTCGACGACGAAGCGCCGGCTTGCGAGGTCGACGACCTGGTCATCGTAGAGGTGGCCGGAGAGATCTCCCCGGCGGTCAAGCAAATGACGGTTGCCGTCAGCGGAACGTCGATCGGGGGAGTCTTTCACGACCGTACGCCCCGCCGGTTCGACCGGCTTGACCTCGCGGTCGACGGCCCGGTGGAGCCCGGGCCCGCCCTGGTGCTGCCGCTGCGTGCCGCCGACACTGTTGCCGGTGTGCTGGTCGCACTTCGCAGTGCCGATGAACAGCCGTTCAGCGACAAACAGCTCGATATGATGGCCGCCTTCGCTGACCAGGCTGCGCTCGCCTGGCGGCTGGCGACCGCGCAGCGACAGATGCGAGAAGTGGAGATCCTGACCGATCGCGACCGGATCGCACGTGATCTGCATGACCACGTCATCCAGCGGCTCTTCGCAGTCGGGCTCACCCTGCAGGGTGCCGCTCCGCGAGCACGTGTCCCCGCCGTCCGGGAATCCATCTACAGCAGCATCGACGATCTCCAGGAAATCATTCAGGAGATTCGATCTGCGATCTTCGACCTACACGCCGGGCCCTCCCGGGCGACGGGTCTGCGCCACCGACTGGACAAGGTCATCGACCAACTCGCGATCCCCGCGCTGCACACCACGGTCCAGTACACGGGCCCGCTGTCCGTTGTCGACACCGTCCTGGCCAACCACGCCGAAGCGGTTCTGCGGGAGGCGGTTAGCAACGCTGTCCGGCACGCGAACGCGACCAGCCTGGCCATCAACGTCAGCGTCGAGGATGATGTGCGGGTCGAGGTCGTCGACGACGGTGTCGGCATCTCCGGCGACATCACCGAAAGCGGCCTGCGCAATCTCCGCCAGCGTGCCGACGACGCGGGCGGCGAATTCACAGTCGAGAACATGCCGACCGGAGGCACCTTGCTGCGGTGGTCTGCACCGCTGCGCTG
Drug Resistance: Check for drug resistance association at TBDREAMDB
Mutations: Check for mutants available at TARGET

Function

Interacts with the two-component regulatory system DevR/DevS (DosR/DosS) involved in onset of the dormancy response. Required for full induction of the DevR (DosR) regulon; required during early adaptation to anaerobiosis, to start induction of the DevR regulon (PubMed:19487478). May act as a direct hypoxia/oxygen sensor (PubMed:17609369, PubMed:17600145, PubMed:28977726). O(2) acts as a switch, with the Fe(2+)-O(2)-bound protein inactive in autophosphorylation (PubMed:17600145). Autophosphorylates under anaerobic but not aerobic conditions, binding of NO or CO has no effect on autophosphorylation (PubMed:17600145). Binds a number of gases; O(2), NO, CO (PubMed:17609369, PubMed:17600145). May be a secondary sensor for CO (PubMed:18400743). Donates a phosphate group to transcriptional regulator DevR (DosR) (PubMed:15135056, PubMed:15033981, PubMed:28977726). {ECO:0000269|PubMed:15033981, ECO:0000269|PubMed:15135056, ECO:0000269|PubMed:17600145, ECO:0000269|PubMed:17609369, ECO:0000269|PubMed:18400743, ECO:0000269|PubMed:18474359, ECO:0000269|PubMed:19487478, ECO:0000269|PubMed:28977726}.

Family

Unknown

GO

protein dimerization activity GO:0046983 molecular_function
protein autophosphorylation GO:0046777 biological_process
heme binding GO:0020037 molecular_function
magnesium ion binding GO:0000287 molecular_function
oxygen sensor activity GO:0019826 molecular_function
oxygen binding GO:0019825 molecular_function
ATP binding GO:0005524 molecular_function
calcium ion binding GO:0005509 molecular_function
detection of hypoxia GO:0070483 biological_process
cytoplasm GO:0005737 cellular_component
nitric oxide binding GO:0070026 molecular_function
carbon monoxide binding GO:0070025 molecular_function
phosphorelay sensor kinase activity GO:0000155 molecular_function
protein histidine kinase activity GO:0004673 molecular_function
protein kinase activity GO:0004672 molecular_function
integral component of membrane GO:0016021 cellular_component

InterPro

UniProt: P9WGK1
GenBank: Rv2027c
EnsemblBacteria: Rv2027c
Mycobrowser: Rv2027c

Summary

Name: Oxygen sensor histidine kinase response regulator DosT (EC 2.7.13.3)
Family: Unknown
Protein Sequence: MTHPDRANVNPGSPPLRETLSQLRLRELLLEVQDRIEQIVEGRDRLDGLIDAILAITSGLKLDATLRAIVHTAAELVDARYGALGVRGYDHRLVEFVYEGIDEETRHLIGSLPEGRGVLGALIEEPKPIRLDDISRHPASVGFPLHHPPMRTFLGVPVRIRDEVFGNLYLTEKADGQPFSDDDEVLVQALAAAAGIAVDNARLFEESRTREAWIEATRDIGTQMLAGADPAMVFRLIAEEALTLMAGAATLVAVPLDDEAPACEVDDLVIVEVAGEISPAVKQMTVAVSGTSIGGVFHDRTPRRFDRLDLAVDGPVEPGPALVLPLRAADTVAGVLVALRSADEQPFSDKQLDMMAAFADQAALAWRLATAQRQMREVEILTDRDRIARDLHDHVIQRLFAVGLTLQGAAPRARVPAVRESIYSSIDDLQEIIQEIRSAIFDLHAGPSRATGLRHRLDKVIDQLAIPALHTTVQYTGPLSVVDTVLANHAEAVLREAVSNAVRHANATSLAINVSVEDDVRVEVVDDGVGISGDITESGLRNLRQRADDAGGEFTVENMPTGGTLLRWSAPLR
Mass: 62,169 Da
Length: 573 Aa

Rv2027c doesn't seem to be a targeted by any drug.

Rv2027c doesn't seem to be involved in any pathway.

Activation of ATP binding for the autophosphorylation of DosS, a Mycobacterium tuberculosis histidine kinase lacking an ATP lid motif.: J Biol Chem. 2013 May 3;288(18):12437-47. doi: 10.1074/jbc.M112.442467. Epub 2013 Mar 13.
2.3 A X-ray structure of the heme-bound GAF domain of sensory histidine kinase DosT of Mycobacterium tuberculosis.: Biochemistry. 2008 Nov 25;47(47):12523-31. doi: 10.1021/bi8012356.
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.
Blockage of the channel to heme by the E87 side chain in the GAF domain of Mycobacterium tuberculosis DosS confers the unique sensitivity of DosS to oxygen.: FEBS Lett. 2011 Jun 23;585(12):1873-8. doi: 10.1016/j.febslet.2011.04.050. Epub 2011 Apr 27.
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.
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.
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.
DosT and DevS are oxygen-switched kinases in Mycobacterium tuberculosis.: Protein Sci. 2007 Aug;16(8):1708-19. doi: 10.1110/ps.072897707. Epub 2007 Jun 28.
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.
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.
Cross talk between DevS sensor kinase homologue, Rv2027c, and DevR response regulator of Mycobacterium tuberculosis.: FEBS Lett. 2004 May 7;565(1-3):75-80. doi: 10.1016/j.febslet.2004.02.092.
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.: Nature. 1998 Jun 11;393(6685):537-44. doi: 10.1038/31159.