DEVS_MYCTU
ID DEVS_MYCTU Reviewed; 578 AA.
AC P9WGK3; L0TBM4; P95194; Q79CX7; Q7D626;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=Oxygen sensor histidine kinase response regulator DevS/DosS {ECO:0000303|PubMed:28977726};
DE EC=2.7.13.3 {ECO:0000269|PubMed:15033981};
GN Name=devS {ECO:0000303|PubMed:10970762}; Synonyms=dosS;
GN OrderedLocusNames=Rv3132c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-116, AND OPERON STRUCTURE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10970762; DOI=10.1054/tuld.2000.0240;
RA Dasgupta N., Kapur V., Singh K.K., Das T.K., Sachdeva S., Jyothisri K.,
RA Tyagi J.S.;
RT "Characterization of a two-component system, devR-devS, of Mycobacterium
RT tuberculosis.";
RL Tuber. Lung Dis. 80:141-159(2000).
RN [3]
RP FUNCTION, REGULON, INDUCTION BY HYPOXIA, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11416222; DOI=10.1073/pnas.121172498;
RA Sherman D.R., Voskuil M., Schnappinger D., Liao R., Harrell M.I.,
RA Schoolnik G.K.;
RT "Regulation of the Mycobacterium tuberculosis hypoxic response gene
RT encoding alpha -crystallin.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:7534-7539(2001).
RN [4]
RP FUNCTION, INDUCTION BY NITRIC OXIDE (NO) AND BY HYPOXIA, AND DORMANCY
RP REGULON.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12953092; DOI=10.1084/jem.20030205;
RA Voskuil M.I., Schnappinger D., Visconti K.C., Harrell M.I., Dolganov G.M.,
RA Sherman D.R., Schoolnik G.K.;
RT "Inhibition of respiration by nitric oxide induces a Mycobacterium
RT tuberculosis dormancy program.";
RL J. Exp. Med. 198:705-713(2003).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, REGULON, PHOSPHORYLATION AT HIS-395,
RP AUTOPHOSPHORYLATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 395-HIS--HIS-397.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15033981; DOI=10.1074/jbc.m401230200;
RA Roberts D.M., Liao R.P., Wisedchaisri G., Hol W.G., Sherman D.R.;
RT "Two sensor kinases contribute to the hypoxic response of Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 279:23082-23087(2004).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT HIS-395,
RP AUTOPHOSPHORYLATION, COFACTOR, AND MUTAGENESIS OF HIS-395; HIS-397 AND
RP ASN-503.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15073296; DOI=10.1099/mic.0.26218-0;
RA Saini D.K., Malhotra V., Dey D., Pant N., Das T.K., Tyagi J.S.;
RT "DevR-DevS is a bona fide two-component system of Mycobacterium
RT tuberculosis that is hypoxia-responsive in the absence of the DNA-binding
RT domain of DevR.";
RL Microbiology 150:865-875(2004).
RN [7]
RP HEME COFACTOR, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-139 AND
RP HIS-149.
RX PubMed=16213520; DOI=10.1016/j.jmb.2005.09.011;
RA Sardiwal S., Kendall S.L., Movahedzadeh F., Rison S.C., Stoker N.G.,
RA Djordjevic S.;
RT "A GAF domain in the hypoxia/NO-inducible Mycobacterium tuberculosis DosS
RT protein binds haem.";
RL J. Mol. Biol. 353:929-936(2005).
RN [8]
RP FUNCTION AS AN OXYGEN SENSOR, HEME COFACTOR, BINDING OF CN; N(3); CO; O(2)
RP AND NO, AND MUTAGENESIS OF HIS-149.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17371046; DOI=10.1021/bi602422p;
RA Ioanoviciu A., Yukl E.T., Moenne-Loccoz P., de Montellano P.R.;
RT "DevS, a heme-containing two-component oxygen sensor of Mycobacterium
RT tuberculosis.";
RL Biochemistry 46:4250-4260(2007).
RN [9]
RP FUNCTION AS A REDOX SENSOR, LIGAND-BINDING, AND HEME COFACTOR.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17609369; DOI=10.1073/pnas.0705054104;
RA Kumar A., Toledo J.C., Patel R.P., Lancaster J.R. Jr., Steyn A.J.;
RT "Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia
RT sensor.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:11568-11573(2007).
RN [10]
RP FUNCTION AS AN OXYGEN SENSOR, HEME COFACTOR, COFACTOR, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, AND LIGAND-BINDING.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17600145; DOI=10.1110/ps.072897707;
RA Sousa E.H., Tuckerman J.R., Gonzalez G., Gilles-Gonzalez M.A.;
RT "DosT and DevS are oxygen-switched kinases in Mycobacterium tuberculosis.";
RL Protein Sci. 16:1708-1719(2007).
RN [11]
RP FUNCTION, MUTAGENESIS OF TYR-171, AND LIGAND-BINDING.
RX PubMed=18975917; DOI=10.1021/bi801234w;
RA Yukl E.T., Ioanoviciu A., Nakano M.M., de Montellano P.R.,
RA Moenne-Loccoz P.;
RT "A distal tyrosine residue is required for ligand discrimination in DevS
RT from Mycobacterium tuberculosis.";
RL Biochemistry 47:12532-12539(2008).
RN [12]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [13]
RP FUNCTION IN CARBON MONOXIDE (CO) RESPONSE, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18474359; DOI=10.1016/j.chom.2008.03.007;
RA Shiloh M.U., Manzanillo P., Cox J.S.;
RT "Mycobacterium tuberculosis senses host-derived carbon monoxide during
RT macrophage infection.";
RL Cell Host Microbe 3:323-330(2008).
RN [14]
RP INDUCTION BY CARBON MONOXIDE (CO), DISRUPTION PHENOTYPE, AND ROLE IN
RP DORMANCY REGULON.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18400743; DOI=10.1074/jbc.m802274200;
RA Kumar A., Deshane J.S., Crossman D.K., Bolisetty S., Yan B.S., Kramnik I.,
RA Agarwal A., Steyn A.J.;
RT "Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium
RT tuberculosis dormancy regulon.";
RL J. Biol. Chem. 283:18032-18039(2008).
RN [15]
RP FUNCTION, HEME COFACTOR, DOMAIN, AND MUTAGENESIS OF TYR-171.
RX PubMed=19463006; DOI=10.1021/bi802309y;
RA Ioanoviciu A., Meharenna Y.T., Poulos T.L., Ortiz de Montellano P.R.;
RT "DevS oxy complex stability identifies this heme protein as a gas sensor in
RT Mycobacterium tuberculosis dormancy.";
RL Biochemistry 48:5839-5848(2009).
RN [16]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=19487478; DOI=10.1128/iai.01449-08;
RA Honaker R.W., Leistikow R.L., Bartek I.L., Voskuil M.I.;
RT "Unique roles of DosT and DosS in DosR regulon induction and Mycobacterium
RT tuberculosis dormancy.";
RL Infect. Immun. 77:3258-3263(2009).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [18]
RP FUNCTION, MUTAGENESIS OF GLU-87; HIS-89 AND ARG-204, AND LIGAND-BINDING.
RC STRAIN=H37Rv;
RX PubMed=27235395; DOI=10.1074/jbc.m116.724815;
RA Basudhar D., Madrona Y., Yukl E.T., Sivaramakrishnan S., Nishida C.R.,
RA Moenne-Loccoz P., Ortiz de Montellano P.R.;
RT "Distal hydrogen-bonding interactions in ligand sensing and signaling by
RT Mycobacterium tuberculosis DosS.";
RL J. Biol. Chem. 291:16100-16111(2016).
RN [19]
RP FUNCTION.
RC STRAIN=H37Rv;
RX PubMed=28977726; DOI=10.1111/febs.14284;
RA Sousa E.H.S., Gonzalez G., Gilles-Gonzalez M.A.;
RT "Target DNA stabilizes Mycobacterium tuberculosis DevR/DosR phosphorylation
RT by the full-length oxygen sensors DevS/DosS and DosT.";
RL FEBS J. 284:3954-3967(2017).
RN [20]
RP REVIEW.
RX PubMed=25002970; DOI=10.3390/bios3030259;
RA Sivaramakrishnan S., de Montellano P.R.;
RT "The DosS-DosT/DosR mycobacterial sensor system.";
RL Biosensors 3:259-282(2013).
RN [21] {ECO:0007744|PDB:2W3D, ECO:0007744|PDB:2W3E, ECO:0007744|PDB:2W3F, ECO:0007744|PDB:2W3G, ECO:0007744|PDB:2W3H}
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 63-210 IN HEME-BOUND; REDUCED;
RP OXIDIZED AND CYANIDE-BOUND FORMS, AND REDUCTION BY FLAVIN NUCLEOTIDES.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19276084; DOI=10.1074/jbc.m808905200;
RA Cho H.Y., Cho H.J., Kim Y.M., Oh J.I., Kang B.S.;
RT "Structural insight into the heme-based redox sensing by DosS from
RT Mycobacterium tuberculosis.";
RL J. Biol. Chem. 284:13057-13067(2009).
RN [22] {ECO:0007744|PDB:2Y79, ECO:0007744|PDB:2Y8H}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 63-210 IN COMPLEX WITH HEME.
RC STRAIN=H37Rv;
RX PubMed=21536032; DOI=10.1016/j.febslet.2011.04.050;
RA Cho H.Y., Cho H.J., Kim M.H., Kang B.S.;
RT "Blockage of the channel to heme by the E87 side chain in the GAF domain of
RT Mycobacterium tuberculosis DosS confers the unique sensitivity of DosS to
RT oxygen.";
RL FEBS Lett. 585:1873-1878(2011).
RN [23] {ECO:0007744|PDB:3ZXO}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 454-578 IN COMPLEX WITH ZINC,
RP SUBUNIT, DOMAIN, MUTAGENESIS OF HIS-395; ARG-440; CYS-524 AND GLU-537, AND
RP ATP-BINDING.
RC STRAIN=H37Rv;
RX PubMed=23486471; DOI=10.1074/jbc.m112.442467;
RA Cho H.Y., Lee Y.H., Bae Y.S., Kim E., Kang B.S.;
RT "Activation of ATP binding for the autophosphorylation of DosS, a
RT Mycobacterium tuberculosis histidine kinase lacking an ATP lid motif.";
RL J. Biol. Chem. 288:12437-12447(2013).
RN [24] {ECO:0007744|PDB:4YNR, ECO:0007744|PDB:4YOF}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 63-210 IN COMPLEX WITH HEME AND
RP CO OR NO.
RX PubMed=27729224; DOI=10.1016/j.abb.2016.10.005;
RA Madrona Y., Waddling C.A., Ortiz de Montellano P.R.;
RT "Crystal structures of the CO- and NO-bound DosS GAF-A domain and
RT implications for DosS signaling in Mycobacterium tuberculosis.";
RL Arch. Biochem. Biophys. 612:1-8(2016).
CC -!- FUNCTION: Member of the two-component regulatory system DevR/DevS
CC (DosR/DosS) involved in onset of the dormancy response
CC (PubMed:12953092). Regulates an approximately 48-member regulon
CC (PubMed:12953092, PubMed:11416222, PubMed:15033981, PubMed:18400743).
CC Required for full induction of the DevR (DosR) regulon; acts later than
CC DosT to positively regulate expression of the DevR regulon during
CC adaptation to anaerobiosis (PubMed:19487478). Characterized as an
CC oxygen sensor; O(2) acts as a switch, with O(2)-bound Fe(2+) protein
CC inactive in autophosphorylation (PubMed:17371046, PubMed:17600145,
CC PubMed:18975917, PubMed:19463006, PubMed:28977726). Has also been
CC suggested to act as a redox sensor, or perhaps as a dual oxygen/redox
CC sensor (PubMed:17609369). Autophosphorylates under anaerobic but not
CC aerobic conditions, binding of NO or CO does not dramatically change
CC the level of autophosphorylation of Fe(2+) protein, binding of O(2)
CC inactivates kinase activity (PubMed:17600145, PubMed:18975917,
CC PubMed:27235395). Binds O(2), NO, CO (PubMed:17371046, PubMed:17609369,
CC PubMed:17600145, PubMed:18975917, PubMed:27235395). It is probably
CC reduced by flavin nucleotides such as FMN and FAD (PubMed:19276084).
CC May be the primary sensor for CO (PubMed:18400743). Donates a phosphate
CC group to transcriptional regulator DevR (DosR) (PubMed:15033981,
CC PubMed:15073296, PubMed:28977726). {ECO:0000269|PubMed:11416222,
CC ECO:0000269|PubMed:12953092, ECO:0000269|PubMed:15033981,
CC ECO:0000269|PubMed:15073296, ECO:0000269|PubMed:17371046,
CC ECO:0000269|PubMed:17600145, ECO:0000269|PubMed:17609369,
CC ECO:0000269|PubMed:18400743, ECO:0000269|PubMed:18474359,
CC ECO:0000269|PubMed:18975917, ECO:0000269|PubMed:19463006,
CC ECO:0000269|PubMed:19487478, ECO:0000269|PubMed:27235395,
CC ECO:0000269|PubMed:28977726}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + protein L-histidine = ADP + protein N-phospho-L-
CC histidine.; EC=2.7.13.3; Evidence={ECO:0000269|PubMed:15033981};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15073296, ECO:0000269|PubMed:17600145};
CC Note=Mn(2+) will also substitute in autophosphorylation assays, while
CC Ca(2+) is a poor substitute (PubMed:17600145).
CC {ECO:0000269|PubMed:17600145};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:16213520, ECO:0000269|PubMed:17371046,
CC ECO:0000269|PubMed:17600145, ECO:0000269|PubMed:19463006,
CC ECO:0000269|PubMed:21536032, ECO:0000269|PubMed:27729224};
CC Note=Binds 1 heme group per monomer (PubMed:16213520, PubMed:17371046,
CC PubMed:17600145, PubMed:21536032, PubMed:27729224).
CC {ECO:0000269|PubMed:16213520, ECO:0000269|PubMed:17371046,
CC ECO:0000269|PubMed:17600145, ECO:0000269|PubMed:21536032,
CC ECO:0000269|PubMed:27729224};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=73 uM for ATP for autophosphorylation by deoxy-DevS
CC {ECO:0000269|PubMed:17600145};
CC -!- SUBUNIT: The isolated histidine kinase core (HKC, residues 386-578) is
CC a dimer and autophosphorylates, suggesting the protein may function as
CC a homodimer (PubMed:23486471). {ECO:0000269|PubMed:23486471}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:16213520,
CC ECO:0000305|PubMed:17600145}.
CC -!- INDUCTION: A member of the dormancy regulon, expression is controlled
CC by devR (PubMed:12953092, PubMed:19487478). Induced in response to
CC reduced oxygen tension (hypoxia) (PubMed:11416222, PubMed:12953092,
CC PubMed:19487478). Induced in response to low levels of nitric oxide
CC (NO) and carbon monoxide (CO) (PubMed:12953092, PubMed:18400743). It is
CC hoped that this regulon will give insight into the latent, or dormant
CC phase of infection. Member of the Rv3134c-devR-devS operon
CC (PubMed:10970762). {ECO:0000269|PubMed:10970762,
CC ECO:0000269|PubMed:11416222, ECO:0000269|PubMed:12953092,
CC ECO:0000269|PubMed:18400743, ECO:0000269|PubMed:19487478}.
CC -!- DOMAIN: The first GAF domain protects the heme moiety from auto-
CC oxidation, contributing to the full-length protein's very long half-
CC life (more than 36 hours in buffers without transition metals)
CC (PubMed:19463006). The isolated ATP-binding subdomain (residues 454-
CC 578) crystallized in a closed form that is unable to bind ATP,
CC suggesting that ATP-binding requires conformational changes in this
CC loop region; in this closed conformation it binds a zinc atom
CC (PubMed:23486471). The isolated histidine kinase core (HKC, residues
CC 386-578) both autophosphorylates and phosphorylates the isolated
CC histidine acceptor subdomain (residues 386-452) (PubMed:23486471). The
CC relative arrangements of the 2 subdomains of the HKC may control not
CC only kinase activity but exposure of the ATP binding site
CC (PubMed:23486471). {ECO:0000269|PubMed:19463006,
CC ECO:0000269|PubMed:23486471}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene show no changes in gene
CC induction following hypoxia, or exposure to NO or CO (PubMed:11416222,
CC PubMed:15033981, PubMed:18474359). Another publication shows a severely
CC attenuated response to CO (PubMed:18400743). Cells lacking both this
CC gene and DosT have no response to hypoxia, or exposure to NO or CO
CC showing both proteins are required for the hypoxic, NO and CO responses
CC (PubMed:15033981). 95% decreased induction of the DevR (DosR) regulon
CC during anaerobic growth, 50% decreased induction of the DevR regulon
CC upon exposure to NO during aerobic growth (PubMed:19487478).
CC {ECO:0000269|PubMed:11416222, ECO:0000269|PubMed:15033981,
CC ECO:0000269|PubMed:18400743, ECO:0000269|PubMed:18474359,
CC ECO:0000269|PubMed:19487478}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000305|PubMed:19099550}.
CC -!- MISCELLANEOUS: A tyrosine residue (Tyr-171) is required for
CC discrimination between bound gaseous ligands (PubMed:18975917). The Tyr
CC is part of a probable hydrogen bonding network which includes Glu-87,
CC His-89 and Arg-204 that is probably also important for signaling to the
CC kinase domain (PubMed:19276084, PubMed:27235395).
CC {ECO:0000269|PubMed:18975917, ECO:0000305|PubMed:19276084,
CC ECO:0000305|PubMed:27235395}.
CC -!- MISCELLANEOUS: The dev nomenclature derives from the increased
CC expression (differentially expressed in virulent strain, dev) of these
CC genes in virulent H37Rv versus avirulent H37Ra. The dos nomenclature
CC derives from experiments in M.bovis showing the same genes are
CC essential for dormancy survival. {ECO:0000305|PubMed:25002970}.
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DR EMBL; AL123456; CCP45942.1; -; Genomic_DNA.
DR EMBL; U22037; AAD17453.1; -; Genomic_DNA.
DR PIR; E70645; E70645.
DR RefSeq; NP_217648.1; NC_000962.3.
DR RefSeq; WP_003899933.1; NZ_NVQJ01000019.1.
DR PDB; 2W3D; X-ray; 2.00 A; A/B=63-210.
DR PDB; 2W3E; X-ray; 1.60 A; A/B=63-210.
DR PDB; 2W3F; X-ray; 1.60 A; A/B=63-210.
DR PDB; 2W3G; X-ray; 1.40 A; A/B=63-210.
DR PDB; 2W3H; X-ray; 1.80 A; A/B=63-210.
DR PDB; 2Y79; X-ray; 1.80 A; A/B=63-210.
DR PDB; 2Y8H; X-ray; 1.90 A; A/B=63-210.
DR PDB; 3ZXO; X-ray; 1.90 A; A/B=454-578.
DR PDB; 4YNR; X-ray; 1.92 A; A/B=63-210.
DR PDB; 4YOF; X-ray; 1.90 A; A/B=63-210.
DR PDBsum; 2W3D; -.
DR PDBsum; 2W3E; -.
DR PDBsum; 2W3F; -.
DR PDBsum; 2W3G; -.
DR PDBsum; 2W3H; -.
DR PDBsum; 2Y79; -.
DR PDBsum; 2Y8H; -.
DR PDBsum; 3ZXO; -.
DR PDBsum; 4YNR; -.
DR PDBsum; 4YOF; -.
DR AlphaFoldDB; P9WGK3; -.
DR SMR; P9WGK3; -.
DR IntAct; P9WGK3; 1.
DR STRING; 83332.Rv3132c; -.
DR iPTMnet; P9WGK3; -.
DR PaxDb; P9WGK3; -.
DR DNASU; 888829; -.
DR GeneID; 888829; -.
DR KEGG; mtu:Rv3132c; -.
DR TubercuList; Rv3132c; -.
DR eggNOG; COG2203; Bacteria.
DR eggNOG; COG4585; Bacteria.
DR OMA; WIDGSVA; -.
DR PhylomeDB; P9WGK3; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:InterPro.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IDA:MTBBASE.
DR GO; GO:0070025; F:carbon monoxide binding; IDA:MTBBASE.
DR GO; GO:0020037; F:heme binding; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0070026; F:nitric oxide binding; IDA:MTBBASE.
DR GO; GO:0019825; F:oxygen binding; IDA:MTBBASE.
DR GO; GO:0019826; F:oxygen sensor activity; IDA:MTBBASE.
DR GO; GO:0000155; F:phosphorelay sensor kinase activity; IEA:InterPro.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0004672; F:protein kinase activity; IDA:MTBBASE.
DR GO; GO:0051776; P:detection of redox state; IDA:MTBBASE.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MTBBASE.
DR GO; GO:0051775; P:response to redox state; IDA:MTBBASE.
DR Gene3D; 3.30.450.40; -; 2.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR003018; GAF.
DR InterPro; IPR029016; GAF-like_dom_sf.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR005467; His_kinase_dom.
DR InterPro; IPR011712; Sig_transdc_His_kin_sub3_dim/P.
DR Pfam; PF13185; GAF_2; 2.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF07730; HisKA_3; 1.
DR SMART; SM00065; GAF; 2.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR PROSITE; PS50109; HIS_KIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cytoplasm; Heme; Iron; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Transferase; Two-component regulatory system.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..578
FT /note="Oxygen sensor histidine kinase response regulator
FT DevS/DosS"
FT /id="PRO_0000392623"
FT DOMAIN 63..200
FT /note="GAF 1"
FT DOMAIN 231..369
FT /note="GAF 2"
FT DOMAIN 383..578
FT /note="Histidine kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT REGION 386..452
FT /note="Histidine acceptor domain"
FT /evidence="ECO:0000305|PubMed:23486471"
FT REGION 454..578
FT /note="ATP-binding domain"
FT /evidence="ECO:0000305|PubMed:23486471"
FT BINDING 149
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:19276084,
FT ECO:0000269|PubMed:21536032, ECO:0000269|PubMed:27729224"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT MOD_RES 395
FT /note="Phosphohistidine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:15033981,
FT ECO:0000305|PubMed:15073296"
FT MUTAGEN 87
FT /note="E->A: No change in autophosphorylation when NO-
FT bound, decreased autophosphorylation in deoxy or CO-bound
FT state, slightly increased activity in O(2)-bound state."
FT /evidence="ECO:0000269|PubMed:27235395"
FT MUTAGEN 87
FT /note="E->D: No change in autophosphorylation when NO-
FT bound, loss of autophosphorylation in deoxy or CO-bound
FT state."
FT /evidence="ECO:0000269|PubMed:27235395"
FT MUTAGEN 87
FT /note="E->G: No change in autophosphorylation when deoxy or
FT NO-bound, decreased autophosphorylation when CO-bound,
FT increased activity in O(2)-bound state."
FT /evidence="ECO:0000269|PubMed:27235395"
FT MUTAGEN 89
FT /note="H->A: No autophosphorylation activity no matter the
FT bound gaseous ligand, protein more easily oxidized to
FT Fe(3+) state."
FT /evidence="ECO:0000269|PubMed:27235395"
FT MUTAGEN 89
FT /note="H->R: Decreased autophosphorylation when CO- or NO-
FT bound, none in the deoxy or O(2)-bound state, protein more
FT easily oxidized to Fe(3+) state."
FT /evidence="ECO:0000269|PubMed:27235395"
FT MUTAGEN 139
FT /note="H->A: No change in heme binding."
FT /evidence="ECO:0000269|PubMed:16213520"
FT MUTAGEN 149
FT /note="H->A: Weaker than wild-type heme binding."
FT /evidence="ECO:0000269|PubMed:16213520,
FT ECO:0000269|PubMed:17371046"
FT MUTAGEN 171
FT /note="Y->F: No autophosphorylation when Fe(2+) protein is
FT bound to CO or NO; no change in autophosphorylation of
FT deoxy-protein. No change in auto-oxidation, slightly higher
FT affinity for O(2) and CO."
FT /evidence="ECO:0000269|PubMed:18975917,
FT ECO:0000269|PubMed:19463006"
FT MUTAGEN 204
FT /note="R->A: No autophosphorylation activity no matter the
FT bound gaseous ligand."
FT /evidence="ECO:0000269|PubMed:27235395"
FT MUTAGEN 395..397
FT /note="HDH->KDK: No autophosphorylation, no transfer to
FT DevR (DosR)."
FT /evidence="ECO:0000269|PubMed:15033981"
FT MUTAGEN 395
FT /note="H->Q: No autophosphorylation. Isolated kinase core
FT binds ATP."
FT /evidence="ECO:0000269|PubMed:15073296,
FT ECO:0000269|PubMed:23486471"
FT MUTAGEN 397
FT /note="H->A,Q: No change in phosphorylation."
FT /evidence="ECO:0000269|PubMed:15073296"
FT MUTAGEN 440
FT /note="R->C: Can form a disulfide bond; when associated
FT with C-537. Loss of autophosphorylation; when associated
FT with C-524 or C-524 and C-537."
FT /evidence="ECO:0000269|PubMed:23486471"
FT MUTAGEN 503
FT /note="N->D: No autophosphorylation."
FT /evidence="ECO:0000269|PubMed:15073296"
FT MUTAGEN 524
FT /note="C->S: Isolated kinase core no longer forms dimers,
FT autophosphorylation unaffected. Decreased
FT autophosphorylation; when associated with C-537. Loss of
FT autophosphorylation; when associated with C-440 or C-440
FT and C-537."
FT /evidence="ECO:0000269|PubMed:23486471"
FT MUTAGEN 537
FT /note="E->C: Can form a disulfide bond; when associated
FT with C-440. Decreased autophosphorylation; when associated
FT with C-524. Loss of autophosphorylation; when associated
FT with C-440 or C-440 and C-524."
FT /evidence="ECO:0000269|PubMed:23486471"
FT HELIX 63..78
FT /evidence="ECO:0007829|PDB:2W3G"
FT STRAND 81..89
FT /evidence="ECO:0007829|PDB:2W3G"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:2W3E"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:2W3G"
FT HELIX 105..111
FT /evidence="ECO:0007829|PDB:2W3G"
FT HELIX 120..126
FT /evidence="ECO:0007829|PDB:2W3G"
FT STRAND 131..135
FT /evidence="ECO:0007829|PDB:2W3G"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:2W3G"
FT STRAND 155..162
FT /evidence="ECO:0007829|PDB:2W3G"
FT STRAND 165..175
FT /evidence="ECO:0007829|PDB:2W3G"
FT HELIX 183..206
FT /evidence="ECO:0007829|PDB:2W3G"
FT HELIX 456..467
FT /evidence="ECO:0007829|PDB:3ZXO"
FT STRAND 472..480
FT /evidence="ECO:0007829|PDB:3ZXO"
FT HELIX 482..484
FT /evidence="ECO:0007829|PDB:3ZXO"
FT HELIX 487..503
FT /evidence="ECO:0007829|PDB:3ZXO"
FT STRAND 512..529
FT /evidence="ECO:0007829|PDB:3ZXO"
FT TURN 535..538
FT /evidence="ECO:0007829|PDB:3ZXO"
FT HELIX 541..552
FT /evidence="ECO:0007829|PDB:3ZXO"
FT STRAND 556..561
FT /evidence="ECO:0007829|PDB:3ZXO"
FT TURN 563..565
FT /evidence="ECO:0007829|PDB:3ZXO"
FT STRAND 568..576
FT /evidence="ECO:0007829|PDB:3ZXO"
SQ SEQUENCE 578 AA; 62241 MW; 4C04B836791B9B32 CRC64;
MTTGGLVDEN DGAAMRPLRH TLSQLRLHEL LVEVQDRVEQ IVEGRDRLDG LVEAMLVVTA
GLDLEATLRA IVHSATSLVD ARYGAMEVHD RQHRVLHFVY EGIDEETVRR IGHLPKGLGV
IGLLIEDPKP LRLDDVSAHP ASIGFPPYHP PMRTFLGVPV RVRDESFGTL YLTDKTNGQP
FSDDDEVLVQ ALAAAAGIAV ANARLYQQAK ARQSWIEATR DIATELLSGT EPATVFRLVA
AEALKLTAAD AALVAVPVDE DMPAADVGEL LVIETVGSAV ASIVGRTIPV AGAVLREVFV
NGIPRRVDRV DLEGLDELAD AGPALLLPLR ARGTVAGVVV VLSQGGPGAF TDEQLEMMAA
FADQAALAWQ LATSQRRMRE LDVLTDRDRI ARDLHDHVIQ RLFAIGLALQ GAVPHERNPE
VQQRLSDVVD DLQDVIQEIR TTIYDLHGAS QGITRLRQRI DAAVAQFADS GLRTSVQFVG
PLSVVDSALA DQAEAVVREA VSNAVRHAKA STLTVRVKVD DDLCIEVTDN GRGLPDEFTG
SGLTNLRQRA EQAGGEFTLA SVPGASGTVL RWSAPLSQ
