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Protein

Redox sensor histidine kinase response regulator DevS

Gene

devS

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Member of the two-component regulatory system DevR/DevS (DosR/DosS) involved in onset of the dormancy response. May act as a redox sensor (rather than a direct hypoxia sensor); the normal (aerobic growth) state is the Fe3+ form, while the reduced (anaerobic growth) Fe2+ form is probably active for phosphate transfer. It is probably reduced by flavin nucleotides such as FMN and FAD. May be the primary sensor for CO. Donates a phosphate group to DevR (DosR).3 Publications

Catalytic activityi

ATP + protein L-histidine = ADP + protein N-phospho-L-histidine.

Cofactori

Protein has several cofactor binding sites:
  • Mg2+
  • hemeNote: Binds 1 heme group per monomer.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi149 – 1491Iron (heme axial ligand)

GO - Molecular functioni

  • ATP binding Source: MTBBASE
  • carbon monoxide binding Source: MTBBASE
  • heme binding Source: MTBBASE
  • magnesium ion binding Source: MTBBASE
  • nitric oxide binding Source: MTBBASE
  • oxygen binding Source: MTBBASE
  • oxygen sensor activity Source: MTBBASE
  • phosphorelay sensor kinase activity Source: InterPro
  • protein kinase activity Source: MTBBASE

GO - Biological processi

  • detection of hypoxia Source: InterPro
  • detection of redox state Source: MTBBASE
  • growth Source: MTBBASE
  • protein autophosphorylation Source: MTBBASE
  • response to redox state Source: MTBBASE
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Two-component regulatory system

Keywords - Ligandi

Heme, Iron, Magnesium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Redox sensor histidine kinase response regulator DevS (EC:2.7.13.3)
Gene namesi
Name:devS
Synonyms:dosS
Ordered Locus Names:Rv3132c
OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Taxonomic identifieri83332 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
Proteomesi
  • UP000001584 Componenti: Chromosome

Organism-specific databases

TubercuListiRv3132c.

Subcellular locationi

GO - Cellular componenti

  • cell wall Source: MTBBASE
  • cytoplasm Source: UniProtKB-SubCell
  • integral component of membrane Source: InterPro
  • plasma membrane Source: MTBBASE
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Cells lacking this gene show no changes in gene induction following hypoxia, or exposure to NO or CO (PubMed:18474359); another publication shows a severely attenuated response to CO (PubMed:18400743). Cells lacking both this gene and DosT have no response to hypoxia, or exposure to NO or CO showing both proteins are required for the hypoxic, NO and CO responses.4 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi139 – 1391H → A: No change in heme binding. 1 Publication
Mutagenesisi149 – 1491H → A: Weaker than wild-type hemin binding. 2 Publications
Mutagenesisi395 – 3973HDH → KDK: No autophosphorylation, no transfer to DevR (DosR). 1 Publication
Mutagenesisi395 – 3951H → Q: No autophosphorylation. 1 Publication
Mutagenesisi397 – 3971H → A or Q: No change in phosphorylation. 1 Publication
Mutagenesisi503 – 5031N → D: No autophosphorylation.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 578577Redox sensor histidine kinase response regulator DevSPRO_0000392623Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylthreonineCombined sources
Modified residuei395 – 3951Phosphohistidine; by autocatalysisCurated

Post-translational modificationi

In the presence of oxygen the heme iron is six-coordinated with a water molecule at the distal site, whereas upon reduction in the anaerobic form the iron is five-coordinated. It does not bind oxygen, indicating that it is a redox- rather than hypoxia-sensor.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP9WGK3.

Expressioni

Inductioni

A member of the dormancy regulon. Induced in response to reduced oxygen tension (hypoxia), low levels of nitric oxide (NO) and carbon monoxide (CO). It is hoped that this regulon will give insight into the latent, or dormant phase of infection. Member of the Rv3134c-devR-devS operon.3 Publications

Interactioni

Protein-protein interaction databases

STRINGi83332.Rv3132c.

Structurei

Secondary structure

1
578
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi63 – 7816Combined sources
Beta strandi81 – 899Combined sources
Helixi91 – 933Combined sources
Beta strandi95 – 1028Combined sources
Helixi105 – 1117Combined sources
Helixi120 – 1267Combined sources
Beta strandi131 – 1355Combined sources
Helixi136 – 1383Combined sources
Beta strandi155 – 1628Combined sources
Beta strandi165 – 17511Combined sources
Helixi183 – 20624Combined sources
Helixi456 – 46712Combined sources
Beta strandi472 – 4809Combined sources
Helixi482 – 4843Combined sources
Helixi487 – 50317Combined sources
Beta strandi512 – 52918Combined sources
Turni535 – 5384Combined sources
Helixi541 – 55212Combined sources
Beta strandi556 – 5616Combined sources
Turni563 – 5653Combined sources
Beta strandi568 – 5769Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2W3DX-ray2.00A/B63-210[»]
2W3EX-ray1.60A/B63-210[»]
2W3FX-ray1.60A/B63-210[»]
2W3GX-ray1.40A/B63-210[»]
2W3HX-ray1.80A/B63-210[»]
2Y79X-ray1.80A/B63-210[»]
3ZXOX-ray1.90A/B454-578[»]
4YNRX-ray1.92A/B63-210[»]
4YOFX-ray1.90A/B63-210[»]
ProteinModelPortaliP9WGK3.
SMRiP9WGK3. Positions 63-207, 231-578.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini63 – 200138GAF 1Add
BLAST
Domaini231 – 369139GAF 2Add
BLAST
Domaini383 – 578196Histidine kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 2 GAF domains.Curated
Contains 1 histidine kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG4107EFD. Bacteria.
COG2203. LUCA.
COG4585. LUCA.
KOiK07682.
OMAiDARYCAL.
PhylomeDBiP9WGK3.

Family and domain databases

Gene3Di3.30.450.40. 2 hits.
3.30.565.10. 2 hits.
InterProiIPR027035. DosT/DevS.
IPR003018. GAF.
IPR029016. GAF_dom-like.
IPR003594. HATPase_C.
IPR005467. His_kinase_dom.
IPR011712. Sig_transdc_His_kin_sub3_dim/P.
[Graphical view]
PANTHERiPTHR11347:SF114. PTHR11347:SF114. 2 hits.
PfamiPF13185. GAF_2. 2 hits.
PF02518. HATPase_c. 1 hit.
PF07730. HisKA_3. 1 hit.
[Graphical view]
SMARTiSM00065. GAF. 2 hits.
SM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMiSSF55781. SSF55781. 2 hits.
SSF55874. SSF55874. 1 hit.
PROSITEiPS50109. HIS_KIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P9WGK3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTTGGLVDEN DGAAMRPLRH TLSQLRLHEL LVEVQDRVEQ IVEGRDRLDG
60 70 80 90 100
LVEAMLVVTA GLDLEATLRA IVHSATSLVD ARYGAMEVHD RQHRVLHFVY
110 120 130 140 150
EGIDEETVRR IGHLPKGLGV IGLLIEDPKP LRLDDVSAHP ASIGFPPYHP
160 170 180 190 200
PMRTFLGVPV RVRDESFGTL YLTDKTNGQP FSDDDEVLVQ ALAAAAGIAV
210 220 230 240 250
ANARLYQQAK ARQSWIEATR DIATELLSGT EPATVFRLVA AEALKLTAAD
260 270 280 290 300
AALVAVPVDE DMPAADVGEL LVIETVGSAV ASIVGRTIPV AGAVLREVFV
310 320 330 340 350
NGIPRRVDRV DLEGLDELAD AGPALLLPLR ARGTVAGVVV VLSQGGPGAF
360 370 380 390 400
TDEQLEMMAA FADQAALAWQ LATSQRRMRE LDVLTDRDRI ARDLHDHVIQ
410 420 430 440 450
RLFAIGLALQ GAVPHERNPE VQQRLSDVVD DLQDVIQEIR TTIYDLHGAS
460 470 480 490 500
QGITRLRQRI DAAVAQFADS GLRTSVQFVG PLSVVDSALA DQAEAVVREA
510 520 530 540 550
VSNAVRHAKA STLTVRVKVD DDLCIEVTDN GRGLPDEFTG SGLTNLRQRA
560 570
EQAGGEFTLA SVPGASGTVL RWSAPLSQ
Length:578
Mass (Da):62,241
Last modified:April 16, 2014 - v1
Checksum:i4C04B836791B9B32
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL123456 Genomic DNA. Translation: CCP45942.1.
U22037 Genomic DNA. Translation: AAD17453.1.
PIRiE70645.
RefSeqiNP_217648.1. NC_000962.3.
WP_003899933.1. NZ_KK339370.1.

Genome annotation databases

EnsemblBacteriaiCCP45942; CCP45942; Rv3132c.
GeneIDi888829.
KEGGimtu:Rv3132c.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL123456 Genomic DNA. Translation: CCP45942.1.
U22037 Genomic DNA. Translation: AAD17453.1.
PIRiE70645.
RefSeqiNP_217648.1. NC_000962.3.
WP_003899933.1. NZ_KK339370.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2W3DX-ray2.00A/B63-210[»]
2W3EX-ray1.60A/B63-210[»]
2W3FX-ray1.60A/B63-210[»]
2W3GX-ray1.40A/B63-210[»]
2W3HX-ray1.80A/B63-210[»]
2Y79X-ray1.80A/B63-210[»]
3ZXOX-ray1.90A/B454-578[»]
4YNRX-ray1.92A/B63-210[»]
4YOFX-ray1.90A/B63-210[»]
ProteinModelPortaliP9WGK3.
SMRiP9WGK3. Positions 63-207, 231-578.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi83332.Rv3132c.

Proteomic databases

PaxDbiP9WGK3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiCCP45942; CCP45942; Rv3132c.
GeneIDi888829.
KEGGimtu:Rv3132c.

Organism-specific databases

TubercuListiRv3132c.

Phylogenomic databases

eggNOGiENOG4107EFD. Bacteria.
COG2203. LUCA.
COG4585. LUCA.
KOiK07682.
OMAiDARYCAL.
PhylomeDBiP9WGK3.

Family and domain databases

Gene3Di3.30.450.40. 2 hits.
3.30.565.10. 2 hits.
InterProiIPR027035. DosT/DevS.
IPR003018. GAF.
IPR029016. GAF_dom-like.
IPR003594. HATPase_C.
IPR005467. His_kinase_dom.
IPR011712. Sig_transdc_His_kin_sub3_dim/P.
[Graphical view]
PANTHERiPTHR11347:SF114. PTHR11347:SF114. 2 hits.
PfamiPF13185. GAF_2. 2 hits.
PF02518. HATPase_c. 1 hit.
PF07730. HisKA_3. 1 hit.
[Graphical view]
SMARTiSM00065. GAF. 2 hits.
SM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMiSSF55781. SSF55781. 2 hits.
SSF55874. SSF55874. 1 hit.
PROSITEiPS50109. HIS_KIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 25618 / H37Rv.
  2. "Characterization of a two-component system, devR-devS, of Mycobacterium tuberculosis."
    Dasgupta N., Kapur V., Singh K.K., Das T.K., Sachdeva S., Jyothisri K., Tyagi J.S.
    Tuber. Lung Dis. 80:141-159(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-116, OPERON STRUCTURE.
    Strain: ATCC 25618 / H37Rv.
  3. "Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding alpha -crystallin."
    Sherman D.R., Voskuil M., Schnappinger D., Liao R., Harrell M.I., Schoolnik G.K.
    Proc. Natl. Acad. Sci. U.S.A. 98:7534-7539(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY HYPOXIA, DISRUPTION PHENOTYPE.
    Strain: ATCC 25618 / H37Rv.
  4. "Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program."
    Voskuil M.I., Schnappinger D., Visconti K.C., Harrell M.I., Dolganov G.M., Sherman D.R., Schoolnik G.K.
    J. Exp. Med. 198:705-713(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY NITRIC OXIDE (NO) AND BY HYPOXIA, DORMANCY REGULON.
    Strain: ATCC 25618 / H37Rv.
  5. "Two sensor kinases contribute to the hypoxic response of Mycobacterium tuberculosis."
    Roberts D.M., Liao R.P., Wisedchaisri G., Hol W.G., Sherman D.R.
    J. Biol. Chem. 279:23082-23087(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF 395-HIS--HIS-397.
    Strain: ATCC 25618 / H37Rv.
  6. "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."
    Saini D.K., Malhotra V., Dey D., Pant N., Das T.K., Tyagi J.S.
    Microbiology 150:865-875(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: AUTOPHOSPHORYLATION, COFACTOR, MUTAGENESIS OF HIS-395 AND HIS-397.
    Strain: ATCC 25618 / H37Rv.
  7. "A GAF domain in the hypoxia/NO-inducible Mycobacterium tuberculosis DosS protein binds haem."
    Sardiwal S., Kendall S.L., Movahedzadeh F., Rison S.C., Stoker N.G., Djordjevic S.
    J. Mol. Biol. 353:929-936(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: HEME COFACTOR, MUTAGENESIS OF HIS-139 AND HIS-149.
  8. "DevS, a heme-containing two-component oxygen sensor of Mycobacterium tuberculosis."
    Ioanoviciu A., Yukl E.T., Moenne-Loccoz P., de Montellano P.R.
    Biochemistry 46:4250-4260(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: COFACTOR, BINDING OF CN, N(3), CO, O(2), NO, MUTAGENESIS OF HIS-149.
    Strain: ATCC 25618 / H37Rv.
  9. "Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor."
    Kumar A., Toledo J.C., Patel R.P., Lancaster J.R. Jr., Steyn A.J.
    Proc. Natl. Acad. Sci. U.S.A. 104:11568-11573(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION AS A REDOX SENSOR, BINDING OF NO AND CO, HEME COFACTOR.
    Strain: ATCC 25618 / H37Rv.
  10. "DosT and DevS are oxygen-switched kinases in Mycobacterium tuberculosis."
    Sousa E.H., Tuckerman J.R., Gonzalez G., Gilles-Gonzalez M.A.
    Protein Sci. 16:1708-1719(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: LIGAND BINDING.
    Strain: ATCC 25618 / H37Rv.
  11. "targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis."
    Raman K., Yeturu K., Chandra N.
    BMC Syst. Biol. 2:109-109(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
  12. "Mycobacterium tuberculosis senses host-derived carbon monoxide during macrophage infection."
    Shiloh M.U., Manzanillo P., Cox J.S.
    Cell Host Microbe 3:323-330(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CARBON MONOXIDE (CO) RESPONSE, DISRUPTION PHENOTYPE.
    Strain: ATCC 25618 / H37Rv.
  13. "Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium tuberculosis dormancy regulon."
    Kumar A., Deshane J.S., Crossman D.K., Bolisetty S., Yan B.S., Kramnik I., Agarwal A., Steyn A.J.
    J. Biol. Chem. 283:18032-18039(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY CARBON MONOXIDE (CO), DISRUPTION PHENOTYPE, ROLE IN DORMANCY REGULON.
    Strain: ATCC 25618 / H37Rv.
  14. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Strain: ATCC 25618 / H37Rv.
  15. "Structural insight into the heme-based redox sensing by DosS from Mycobacterium tuberculosis."
    Cho H.Y., Cho H.J., Kim Y.M., Oh J.I., Kang B.S.
    J. Biol. Chem. 284:13057-13067(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 63-210 IN HEME-BOUND, REDUCED, AIR-OXIDIZED, CYANIDE-BOUND FORMS, REDUCTION BY FLAVIN NUCLEOTIDES.
    Strain: ATCC 25618 / H37Rv.

Entry informationi

Entry nameiDEVS_MYCTU
AccessioniPrimary (citable) accession number: P9WGK3
Secondary accession number(s): L0TBM4
, P95194, Q79CX7, Q7D626
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: April 16, 2014
Last modified: May 11, 2016
This is version 19 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Was identified as a high-confidence drug target.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
    Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.