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Protein

Transcriptional regulatory protein DevR (DosR)

Gene

devR

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. When phosphorylated binds the promoter of at least its own and Acr (hspX) gene in response to hypoxia. 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. Accepts a phosphate group from DevS (DosS) and from DosT.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi167 – 18620H-T-H motifPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • DNA binding Source: MTBBASE
  • transcription factor activity, sequence-specific DNA binding Source: MTBBASE

GO - Biological processi

  • dormancy process Source: MTBBASE
  • pathogenesis Source: MTBBASE
  • phosphorelay signal transduction system Source: UniProtKB-KW
  • positive regulation of transcription, DNA-templated Source: MTBBASE
  • regulation of fatty acid metabolic process Source: MTBBASE
  • regulation of response to stress Source: MTBBASE
  • response to hypoxia Source: MTBBASE
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation, Two-component regulatory system

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Transcriptional regulatory protein DevR (DosR)
Gene namesi
Name:devR
Synonyms:dosR
Ordered Locus Names:Rv3133c
OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Taxonomic identifieri83332 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
Proteomesi
  • UP000001584 Componenti: Chromosome

Organism-specific databases

TubercuListiRv3133c.

Subcellular locationi

GO - Cellular componenti

  • cell wall Source: MTBBASE
  • cytosol Source: MTBBASE
  • extracellular space Source: MTBBASE
  • host cell cytoplasmic vesicle Source: UniProtKB-SubCell
  • host cell endosome lumen Source: MTBBASE
  • plasma membrane Source: MTBBASE
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Host cytoplasmic vesicle

Pathology & Biotechi

Disruption phenotypei

Strains deleted for this gene show hypervirulence upon intravenous innoculation in the mouse and DBA/2 model (PubMed:12595424), however contradictory results were shown for using a devR/devS deletion strain in rabbits, guinea pigs and C57BL/6 mice (PubMed:19103767). All studies agree that deletion strains fail to induce the dormancy regulon genes in response to hypoxia, NO, and CO.5 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi8 – 81D → N: No phosphorylation by DevS (DosS). 1 Publication
Mutagenesisi9 – 91D → N: No phosphorylation by DevS (DosS). 1 Publication
Mutagenesisi54 – 541D → E: Able to bind DNA, no longer induces hypoxic response. 2 Publications
Mutagenesisi54 – 541D → V: No phosphorylation by DevS (DosS) nor by DosT. 2 Publications
Mutagenesisi104 – 1041K → E: No phosphorylation by DevS (DosS). 1 Publication
Mutagenesisi198 – 1981T → A: Decreases phosphorylation by PknH. 1 Publication
Mutagenesisi205 – 2051T → A: No phosphorylation by PknH. 1 Publication

Chemistry

ChEMBLiCHEMBL6064.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 217217Transcriptional regulatory protein DevR (DosR)PRO_0000392625Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei54 – 5414-aspartylphosphateCurated
Modified residuei198 – 1981Phosphothreonine; by PknH1 Publication
Modified residuei205 – 2051Phosphothreonine; by PknH1 Publication

Post-translational modificationi

Phosphorylated on aspartate by both DevS (DosS) and DosT. Phosphorylated on threonine by PknH. Phosphorylation by PknH enhances DevR dimerization. Aspartate phosphorylation and threonine phosphorylation cooperatively enhance DevR binding to DNA.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP9WMF9.

PTM databases

iPTMnetiP9WMF9.

Expressioni

Inductioni

A member of the dormancy regulon. Moderately expressed under aerobic conditions, it is strongly 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. Expression under hypoxic conditions, but not aerobically, is autoregulated. Member of the Rv3134c-devR-devS operon.5 Publications

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

STRINGi83332.Rv3133c.

Structurei

Secondary structure

1
217
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi2 – 76Combined sources
Helixi11 – 2212Combined sources
Beta strandi27 – 359Combined sources
Helixi36 – 4611Combined sources
Beta strandi49 – 535Combined sources
Beta strandi55 – 573Combined sources
Helixi62 – 7211Combined sources
Beta strandi77 – 804Combined sources
Helixi81 – 833Combined sources
Beta strandi84 – 863Combined sources
Helixi87 – 9610Combined sources
Helixi101 – 12121Combined sources
Helixi122 – 1243Combined sources
Helixi127 – 14317Combined sources
Turni146 – 1494Combined sources
Helixi152 – 16211Combined sources
Helixi167 – 1748Combined sources
Helixi178 – 19215Combined sources
Helixi199 – 2079Combined sources
Turni208 – 2103Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZLJX-ray2.00A/B/C/D/E/F/G/H144-217[»]
1ZLKX-ray3.10A/B144-217[»]
3C3WX-ray2.20A/B1-217[»]
3C57X-ray1.70A/B144-217[»]
ProteinModelPortaliP9WMF9.
SMRiP9WMF9. Positions 1-211.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini3 – 119117Response regulatoryPROSITE-ProRule annotationAdd
BLAST
Domaini143 – 20866HTH luxR-typePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 HTH luxR-type DNA-binding domain.PROSITE-ProRule annotation
Contains 1 response regulatory domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG4107NGZ. Bacteria.
COG2197. LUCA.
KOiK07695.
OMAiQGNANFH.
PhylomeDBiP9WMF9.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR011006. CheY-like_superfamily.
IPR016032. Sig_transdc_resp-reg_C-effctor.
IPR001789. Sig_transdc_resp-reg_receiver.
IPR000792. Tscrpt_reg_LuxR_C.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00196. GerE. 1 hit.
PF00072. Response_reg. 1 hit.
[Graphical view]
PRINTSiPR00038. HTHLUXR.
SMARTiSM00421. HTH_LUXR. 1 hit.
SM00448. REC. 1 hit.
[Graphical view]
SUPFAMiSSF46894. SSF46894. 1 hit.
SSF52172. SSF52172. 1 hit.
PROSITEiPS00622. HTH_LUXR_1. 1 hit.
PS50043. HTH_LUXR_2. 1 hit.
PS50110. RESPONSE_REGULATORY. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P9WMF9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVKVFLVDDH EVVRRGLVDL LGADPELDVV GEAGSVAEAM ARVPAARPDV
60 70 80 90 100
AVLDVRLPDG NGIELCRDLL SRMPDLRCLI LTSYTSDEAM LDAILAGASG
110 120 130 140 150
YVVKDIKGME LARAVKDVGA GRSLLDNRAA AALMAKLRGA AEKQDPLSGL
160 170 180 190 200
TDQERTLLGL LSEGLTNKQI ADRMFLAEKT VKNYVSRLLA KLGMERRTQA
210
AVFATELKRS RPPGDGP
Length:217
Mass (Da):23,294
Last modified:April 16, 2014 - v1
Checksum:i1BA535C26CC4EB51
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U22037 Genomic DNA. Translation: AAD17452.1.
AL123456 Genomic DNA. Translation: CCP45943.1.
PIRiF70645.
RefSeqiNP_217649.1. NC_000962.3.
WP_003416369.1. NZ_KK339370.1.

Genome annotation databases

EnsemblBacteriaiCCP45943; CCP45943; Rv3133c.
GeneIDi888842.
KEGGimtu:Rv3133c.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U22037 Genomic DNA. Translation: AAD17452.1.
AL123456 Genomic DNA. Translation: CCP45943.1.
PIRiF70645.
RefSeqiNP_217649.1. NC_000962.3.
WP_003416369.1. NZ_KK339370.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZLJX-ray2.00A/B/C/D/E/F/G/H144-217[»]
1ZLKX-ray3.10A/B144-217[»]
3C3WX-ray2.20A/B1-217[»]
3C57X-ray1.70A/B144-217[»]
ProteinModelPortaliP9WMF9.
SMRiP9WMF9. Positions 1-211.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi83332.Rv3133c.

Chemistry

ChEMBLiCHEMBL6064.

PTM databases

iPTMnetiP9WMF9.

Proteomic databases

PaxDbiP9WMF9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiCCP45943; CCP45943; Rv3133c.
GeneIDi888842.
KEGGimtu:Rv3133c.

Organism-specific databases

TubercuListiRv3133c.

Phylogenomic databases

eggNOGiENOG4107NGZ. Bacteria.
COG2197. LUCA.
KOiK07695.
OMAiQGNANFH.
PhylomeDBiP9WMF9.

Miscellaneous databases

PROiP9WMF9.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR011006. CheY-like_superfamily.
IPR016032. Sig_transdc_resp-reg_C-effctor.
IPR001789. Sig_transdc_resp-reg_receiver.
IPR000792. Tscrpt_reg_LuxR_C.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00196. GerE. 1 hit.
PF00072. Response_reg. 1 hit.
[Graphical view]
PRINTSiPR00038. HTHLUXR.
SMARTiSM00421. HTH_LUXR. 1 hit.
SM00448. REC. 1 hit.
[Graphical view]
SUPFAMiSSF46894. SSF46894. 1 hit.
SSF52172. SSF52172. 1 hit.
PROSITEiPS00622. HTH_LUXR_1. 1 hit.
PS50043. HTH_LUXR_2. 1 hit.
PS50110. RESPONSE_REGULATORY. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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], OPERON STRUCTURE, DETECTION IN HUMAN MONOCYTES.
    Strain: ATCC 25618 / H37Rv.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    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.
    Strain: ATCC 25618 / H37Rv.
  4. "Deletion of two-component regulatory systems increases the virulence of Mycobacterium tuberculosis."
    Parish T., Smith D.A., Kendall S., Casali N., Bancroft G.J., Stoker N.G.
    Infect. Immun. 71:1134-1140(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE IN DBA/2 MICE.
    Strain: ATCC 25618 / H37Rv.
  5. "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.
  6. "Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis."
    Park H.D., Guinn K.M., Harrell M.I., Liao R., Voskuil M.I., Tompa M., Schoolnik G.K., Sherman D.R.
    Mol. Microbiol. 48:833-843(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DNA-BINDING, DISRUPTION PHENOTYPE, MUTAGENESIS OF ASP-54.
    Strain: ATCC 27294 / TMC 102 / H37Rv.
  7. "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: PHOSPHORYLATION BY DEVS (DOSS), BY DOST.
    Strain: ATCC 25618 / H37Rv.
  8. "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: PHOSPHORYLATION BY DEVS (DOSS), MUTAGENESIS OF ASP-8; ASP-9; ASP-54 AND LYS-104.
    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: INDUCTION BY CARBON MONOXIDE (CO).
    Strain: ATCC 25618 / H37Rv.
  10. "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: INDUCTION BY CARBON MONOXIDE (CO), DISRUPTION PHENOTYPE.
    Strain: ATCC 25618 / H37Rv.
  11. "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."
    Chauhan S., Tyagi J.S.
    J. Bacteriol. 190:4301-4312(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS A TRANSCRIPTIONAL ACTIVATOR, DNA-BINDING.
    Strain: ATCC 25618 / H37Rv.
  12. "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.
  13. "Role of the dosR-dosS two-component regulatory system in Mycobacterium tuberculosis virulence in three animal models."
    Converse P.J., Karakousis P.C., Klinkenberg L.G., Kesavan A.K., Ly L.H., Allen S.S., Grosset J.H., Jain S.K., Lamichhane G., Manabe Y.C., McMurray D.N., Nuermberger E.L., Bishai W.R.
    Infect. Immun. 77:1230-1237(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE IN GUINEA PIG; MOUSE AND RABBIT.
    Strain: ATCC 25618 / H37Rv.
  14. "Convergence of Ser/Thr and two-component signaling to coordinate expression of the dormancy regulon in Mycobacterium tuberculosis."
    Chao J.D., Papavinasasundaram K.G., Zheng X., Chavez-Steenbock A., Wang X., Lee G.Q., Av-Gay Y.
    J. Biol. Chem. 285:29239-29246(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-198 AND THR-205, MUTAGENESIS OF THR-198 AND THR-205.
    Strain: ATCC 25618 / H37Rv.
  15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Strain: ATCC 25618 / H37Rv.
  16. "Structures of Mycobacterium tuberculosis DosR and DosR-DNA complex involved in gene activation during adaptation to hypoxic latency."
    Wisedchaisri G., Wu M., Rice A.E., Roberts D.M., Sherman D.R., Hol W.G.
    J. Mol. Biol. 354:630-641(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 144-217 WITH AND WITHOUT BOUND DNA.
    Strain: ATCC 25618 / H37Rv.
  17. "Crystal structures of the response regulator DosR from Mycobacterium tuberculosis suggest a helix rearrangement mechanism for phosphorylation activation."
    Wisedchaisri G., Wu M., Sherman D.R., Hol W.G.
    J. Mol. Biol. 378:227-242(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), SUBUNIT.
    Strain: ATCC 25618 / H37Rv.

Entry informationi

Entry nameiDEVR_MYCTU
AccessioniPrimary (citable) accession number: P9WMF9
Secondary accession number(s): L0TBX9
, P95193, Q79CX8, Q7D625
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: April 16, 2014
Last modified: June 8, 2016
This is version 22 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

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.