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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)DescriptionActionsGraphical viewLength
Metal bindingi149Iron (heme axial ligand)1

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

Enzyme and pathway databases

BioCyciMTBH37RV:G185E-7396-MONOMER.

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)DescriptionActionsGraphical viewLength
Mutagenesisi139H → A: No change in heme binding. 1 Publication1
Mutagenesisi149H → A: Weaker than wild-type hemin binding. 2 Publications1
Mutagenesisi395 – 397HDH → KDK: No autophosphorylation, no transfer to DevR (DosR). 1 Publication3
Mutagenesisi395H → Q: No autophosphorylation. 1 Publication1
Mutagenesisi397H → A or Q: No change in phosphorylation. 1 Publication1
Mutagenesisi503N → D: No autophosphorylation. 1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00003926232 – 578Redox sensor histidine kinase response regulator DevSAdd BLAST577

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonineCombined sources1
Modified residuei395Phosphohistidine; by autocatalysisCurated1

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

1578
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi63 – 78Combined sources16
Beta strandi81 – 89Combined sources9
Helixi91 – 93Combined sources3
Beta strandi95 – 102Combined sources8
Helixi105 – 111Combined sources7
Helixi120 – 126Combined sources7
Beta strandi131 – 135Combined sources5
Helixi136 – 138Combined sources3
Beta strandi155 – 162Combined sources8
Beta strandi165 – 175Combined sources11
Helixi183 – 206Combined sources24
Helixi456 – 467Combined sources12
Beta strandi472 – 480Combined sources9
Helixi482 – 484Combined sources3
Helixi487 – 503Combined sources17
Beta strandi512 – 529Combined sources18
Turni535 – 538Combined sources4
Helixi541 – 552Combined sources12
Beta strandi556 – 561Combined sources6
Turni563 – 565Combined sources3
Beta strandi568 – 576Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini63 – 200GAF 1Add BLAST138
Domaini231 – 369GAF 2Add BLAST139
Domaini383 – 578Histidine kinasePROSITE-ProRule annotationAdd BLAST196

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

Gene3Di1.20.1200.10. 1 hit.
3.30.450.40. 2 hits.
3.30.565.10. 1 hit.
InterProiIPR016030. AdoCbl_synth_CblAdoTrfase-like.
IPR027035. 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
PDB 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.
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.

Enzyme and pathway databases

BioCyciMTBH37RV:G185E-7396-MONOMER.

Family and domain databases

Gene3Di1.20.1200.10. 1 hit.
3.30.450.40. 2 hits.
3.30.565.10. 1 hit.
InterProiIPR016030. AdoCbl_synth_CblAdoTrfase-like.
IPR027035. 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...

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: November 30, 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

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.