UniProtKB - P9WGH9 (SIGH_MYCTU)
Protein
ECF RNA polymerase sigma factor SigH
Gene
sigH
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Functioni
Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. Extracytoplasmic function (ECF) sigma factors are held in an inactive form by a cognate anti-sigma factor (RshA) until released. This sigma factor is involved in heat shock and oxidative stress responses; it positively regulates the expression of itself, sigE, sigB and a number of transcriptional regulators as well as other effectors of heat and oxidative stress, leading to direct and indirect control of up to 25% of the bacterial genome. Modulates expression of host genes for intercrine beta (chemokine CC) and apoptosis, altering the host immune response.4 Publications
Miscellaneous
Was identified as a high-confidence drug target.
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 166 – 185 | H-T-H motifBy similarityAdd BLAST | 20 |
GO - Molecular functioni
- DNA binding Source: UniProtKB-KW
- DNA-binding transcription factor activity Source: InterPro
- sigma factor activity Source: UniProtKB-KW
GO - Biological processi
- cellular response to heat Source: MTBBASE
- DNA-templated transcription, initiation Source: InterPro
- regulation of transcription, DNA-templated Source: MTBBASE
- response to heat Source: MTBBASE
- response to nitrosative stress Source: MTBBASE
- response to oxidative stress Source: MTBBASE
Keywordsi
Molecular function | DNA-binding, Sigma factor |
Biological process | Stress response, Transcription, Transcription regulation |
Names & Taxonomyi
Protein namesi | Recommended name: ECF RNA polymerase sigma factor SigHShort name: ECF sigma factor SigH Alternative name(s): Alternative RNA polymerase sigma factor SigH RNA polymerase sigma-H factor Short name: Sigma-H factor |
Gene namesi | Name:sigH Synonyms:rpoE Ordered Locus Names:Rv3223c ORF Names:MTCY07D11.03 |
Organismi | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
Taxonomic identifieri | 83332 [NCBI] |
Taxonomic lineagei | Bacteria › Actinobacteria › Corynebacteriales › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex › |
Proteomesi |
|
Organism-specific databases
TubercuListi | Rv3223c |
Pathology & Biotechi
Disruption phenotypei
Increased susceptibility to oxidative stress (H2O2, cumene hydroperoxide and diamide, PubMed:12123450) and heat shock (45 and 52 degrees Celsius). Loss of stress-induced expression of a number of genes including clpB, dnaK, sigE and trxB (PubMed:11567012), sigB and itself (PubMed:12123450). No effect on infection of human derived macrophages, and murine J774.1 activated and unactivated macrophages (PubMed:12123450).2 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 26 | T → A: No in vitro phosphorylation by PknB; when associated with A-106. 1 Publication | 1 | |
Mutagenesisi | 106 | T → A: No in vitro phosphorylation by PknB; when associated with A-26. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000094004 | 1 – 216 | ECF RNA polymerase sigma factor SigHAdd BLAST | 216 |
Post-translational modificationi
Phosphorylated, possibly on 2 residues, probably by PknB. Phosphorylation of SigH has no effect on interaction with RshA.1 Publication
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | P9WGH9 |
Expressioni
Inductioni
Poorly expressed in exponential phase; induced by heat shock (20-fold, 45 degrees Celsius). Induced 10-fold by the thiol-oxidative agent diamide within 30 minutes of exposure, by 2 hours expression is again normal. Autoregulates its own expression, part of the sigH-rshA operon.2 Publications
Interactioni
Subunit structurei
Interacts transiently with the RNA polymerase catalytic core formed by RpoA, RpoB, RpoC and RpoZ (2 alpha, 1 beta, 1 beta' and 1 omega subunit) to form the RNA polymerase holoenzyme that can initiate transcription.
Interacts (affinity=15 nM) 1:1 (via sigma-70 factor domain-4) with RshA under reducing conditions; the complex is disrupted as temperatures rise. Phosphorylation of RshA decreases its interaction with SigH, leading to increased SigH-mediated transcription.
4 PublicationsProtein-protein interaction databases
IntActi | P9WGH9, 2 interactors |
STRINGi | 83332.Rv3223c |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P9WGH9 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 37 – 99 | Sigma-70 factor domain-2Add BLAST | 63 | |
Regioni | 140 – 191 | Sigma-70 factor domain-4Add BLAST | 52 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 56 – 59 | Polymerase core bindingSequence analysis | 4 |
Domaini
The sigma-70 factor domain-2 mediates sequence-specific interaction with the -10 element in promoter DNA, and plays an important role in melting the double-stranded DNA and the formation of the transcription bubble. The sigma-70 factor domain-2 mediates interaction with the RNA polymerase subunits RpoB and RpoC (By similarity).By similarity
The sigma-70 factor domain-4 contains a helix-turn-helix (H-T-H) motif that mediates interaction with the -35 element in promoter DNA. The domain also mediates interaction with the RNA polymerase subunit RpoA. Interactions between sigma-70 factor domain-4 and anti-sigma factors prevents interaction of sigma factors with the RNA polymerase catalytic core.
Sequence similaritiesi
Phylogenomic databases
eggNOGi | COG1595, Bacteria |
OMAi | TYINLYR |
PhylomeDBi | P9WGH9 |
Family and domain databases
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View protein in InterPro IPR039425, RNA_pol_sigma-70-like IPR014284, RNA_pol_sigma-70_dom IPR014293, RNA_pol_sigma70_actinobac IPR000838, RNA_pol_sigma70_ECF_CS IPR007627, RNA_pol_sigma70_r2 IPR013249, RNA_pol_sigma70_r4_t2 IPR013325, RNA_pol_sigma_r2 IPR013324, RNA_pol_sigma_r3/r4-like IPR036388, WH-like_DNA-bd_sf |
PANTHERi | PTHR43133, PTHR43133, 1 hit |
Pfami | View protein in Pfam PF04542, Sigma70_r2, 1 hit PF08281, Sigma70_r4_2, 1 hit |
SUPFAMi | SSF88659, SSF88659, 1 hit SSF88946, SSF88946, 1 hit |
TIGRFAMsi | TIGR02947, SigH_actino, 1 hit TIGR02937, sigma70-ECF, 1 hit |
PROSITEi | View protein in PROSITE PS01063, SIGMA70_ECF, 1 hit |
i Sequence
Sequence statusi: Complete.
P9WGH9-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MADIDGVTGS AGLQPGPSEE TDEELTARFE RDAIPLLDQL YGGALRMTRN
60 70 80 90 100
PADAEDLLQE TMVKAYAGFR SFRHGTNLKA WLYRILTNTY INSYRKKQRQ
110 120 130 140 150
PAEYPTEQIT DWQLASNAEH SSTGLRSAEV EALEALPDTE IKEALQALPE
160 170 180 190 200
EFRMAVYYAD VEGFPYKEIA EIMDTPIGTV MSRLHRGRRQ LRGLLADVAR
210
DRGFARGEQA HEGVSS
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL123456 Genomic DNA Translation: CCP46040.1 |
PIRi | H70596 |
RefSeqi | NP_217739.1, NC_000962.3 WP_003416897.1, NZ_NVQJ01000003.1 |
Genome annotation databases
EnsemblBacteriai | CCP46040; CCP46040; Rv3223c |
GeneIDi | 23490509 888094 |
KEGGi | mtu:Rv3223c mtv:RVBD_3223c |
PATRICi | fig|83332.111.peg.3600 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL123456 Genomic DNA Translation: CCP46040.1 |
PIRi | H70596 |
RefSeqi | NP_217739.1, NC_000962.3 WP_003416897.1, NZ_NVQJ01000003.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5ZX2 | X-ray | 2.80 | F | 1-216 | [»] | |
5ZX3 | X-ray | 2.75 | F | 1-216 | [»] | |
6JCX | X-ray | 2.90 | F | 1-216 | [»] | |
6JCY | X-ray | 3.11 | F | 1-95 | [»] | |
F | 146-216 | [»] | ||||
6KON | X-ray | 3.00 | F | 1-216 | [»] | |
6KOO | X-ray | 2.80 | F | 1-216 | [»] | |
6KOP | X-ray | 3.30 | F | 1-216 | [»] | |
6KOQ | X-ray | 3.35 | F | 1-216 | [»] | |
SMRi | P9WGH9 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
IntActi | P9WGH9, 2 interactors |
STRINGi | 83332.Rv3223c |
Proteomic databases
PaxDbi | P9WGH9 |
Genome annotation databases
EnsemblBacteriai | CCP46040; CCP46040; Rv3223c |
GeneIDi | 23490509 888094 |
KEGGi | mtu:Rv3223c mtv:RVBD_3223c |
PATRICi | fig|83332.111.peg.3600 |
Organism-specific databases
TubercuListi | Rv3223c |
Phylogenomic databases
eggNOGi | COG1595, Bacteria |
OMAi | TYINLYR |
PhylomeDBi | P9WGH9 |
Family and domain databases
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View protein in InterPro IPR039425, RNA_pol_sigma-70-like IPR014284, RNA_pol_sigma-70_dom IPR014293, RNA_pol_sigma70_actinobac IPR000838, RNA_pol_sigma70_ECF_CS IPR007627, RNA_pol_sigma70_r2 IPR013249, RNA_pol_sigma70_r4_t2 IPR013325, RNA_pol_sigma_r2 IPR013324, RNA_pol_sigma_r3/r4-like IPR036388, WH-like_DNA-bd_sf |
PANTHERi | PTHR43133, PTHR43133, 1 hit |
Pfami | View protein in Pfam PF04542, Sigma70_r2, 1 hit PF08281, Sigma70_r4_2, 1 hit |
SUPFAMi | SSF88659, SSF88659, 1 hit SSF88946, SSF88946, 1 hit |
TIGRFAMsi | TIGR02947, SigH_actino, 1 hit TIGR02937, sigma70-ECF, 1 hit |
PROSITEi | View protein in PROSITE PS01063, SIGMA70_ECF, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SIGH_MYCTU | |
Accessioni | P9WGH9Primary (citable) accession number: P9WGH9 Secondary accession number(s): L0TEP5, O05843, P66807 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 16, 2014 |
Last sequence update: | April 16, 2014 | |
Last modified: | December 2, 2020 | |
This is version 40 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families