SIGH_MYCTU
ID SIGH_MYCTU Reviewed; 216 AA.
AC P9WGH9; L0TEP5; O05843; P66807;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=ECF RNA polymerase sigma factor SigH;
DE Short=ECF sigma factor SigH;
DE AltName: Full=Alternative RNA polymerase sigma factor SigH;
DE AltName: Full=RNA polymerase sigma-H factor;
DE Short=Sigma-H factor;
GN Name=sigH; Synonyms=rpoE; OrderedLocusNames=Rv3223c; ORFNames=MTCY07D11.03;
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 PROTEIN SEQUENCE OF 1-25; 3-44; 46-69 AND 90-196, AND INTERACTION WITH
RP RSHA.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22937074; DOI=10.1371/journal.pone.0043676;
RA Kumar S., Badireddy S., Pal K., Sharma S., Arora C., Garg S.K., Alam M.S.,
RA Agrawal P., Anand G.S., Swaminathan K.;
RT "Interaction of Mycobacterium tuberculosis RshA and SigH is mediated by
RT salt bridges.";
RL PLoS ONE 7:E43676-E43676(2012).
RN [3]
RP INDUCTION BY HEAT SHOCK.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10027986; DOI=10.1046/j.1365-2958.1999.01212.x;
RA Manganelli R., Dubnau E., Tyagi S., Kramer F.R., Smith I.;
RT "Differential expression of 10 sigma factor genes in Mycobacterium
RT tuberculosis.";
RL Mol. Microbiol. 31:715-724(1999).
RN [4]
RP FUNCTION AS A SIGMA FACTOR, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11567012; DOI=10.1128/jb.183.20.6119-6125.2001;
RA Raman S., Song T., Puyang X., Bardarov S., Jacobs W.R. Jr., Husson R.N.;
RT "The alternative sigma factor SigH regulates major components of oxidative
RT and heat stress responses in Mycobacterium tuberculosis.";
RL J. Bacteriol. 183:6119-6125(2001).
RN [5]
RP FUNCTION, REGULON, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12123450; DOI=10.1046/j.1365-2958.2002.03005.x;
RA Manganelli R., Voskuil M.I., Schoolnik G.K., Dubnau E., Gomez M., Smith I.;
RT "Role of the extracytoplasmic-function sigma factor sigma(H) in
RT Mycobacterium tuberculosis global gene expression.";
RL Mol. Microbiol. 45:365-374(2002).
RN [6]
RP FUNCTION AS A SIGMA FACTOR, AND INTERACTION WITH RSHA.
RX PubMed=14617153; DOI=10.1046/j.1365-2958.2003.03739.x;
RA Song T., Dove S.L., Lee K.H., Husson R.N.;
RT "RshA, an anti-sigma factor that regulates the activity of the
RT mycobacterial stress response sigma factor SigH.";
RL Mol. Microbiol. 50:949-959(2003).
RN [7]
RP FUNCTION AS A SIGMA FACTOR, BINDING AFFINITY, AND SUBUNIT.
RX PubMed=16298337; DOI=10.1016/j.bbrc.2005.11.032;
RA Jeong E.H., Son Y.M., Hah Y.S., Choi Y.J., Lee K.H., Song T., Kim D.R.;
RT "RshA mimetic peptides inhibiting the transcription driven by a
RT Mycobacterium tuberculosis sigma factor SigH.";
RL Biochem. Biophys. Res. Commun. 339:392-398(2006).
RN [8]
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 [9]
RP REGULATION, INTERACTION WITH RSHA, PHOSPHORYLATION, AND MUTAGENESIS OF
RP THR-26 AND THR-106.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18728196; DOI=10.1073/pnas.0801143105;
RA Park S.T., Kang C.M., Husson R.N.;
RT "Regulation of the SigH stress response regulon by an essential protein
RT kinase in Mycobacterium tuberculosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:13105-13110(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [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).
CC -!- FUNCTION: Sigma factors are initiation factors that promote the
CC attachment of RNA polymerase to specific initiation sites and are then
CC released. Extracytoplasmic function (ECF) sigma factors are held in an
CC inactive form by a cognate anti-sigma factor (RshA) until released.
CC This sigma factor is involved in heat shock and oxidative stress
CC responses; it positively regulates the expression of itself, sigE, sigB
CC and a number of transcriptional regulators as well as other effectors
CC of heat and oxidative stress, leading to direct and indirect control of
CC up to 25% of the bacterial genome. Modulates expression of host genes
CC for intercrine beta (chemokine CC) and apoptosis, altering the host
CC immune response. {ECO:0000269|PubMed:11567012,
CC ECO:0000269|PubMed:12123450, ECO:0000269|PubMed:14617153,
CC ECO:0000269|PubMed:16298337}.
CC -!- SUBUNIT: Interacts transiently with the RNA polymerase catalytic core
CC formed by RpoA, RpoB, RpoC and RpoZ (2 alpha, 1 beta, 1 beta' and 1
CC omega subunit) to form the RNA polymerase holoenzyme that can initiate
CC transcription. Interacts (affinity=15 nM) 1:1 (via sigma-70 factor
CC domain-4) with RshA under reducing conditions; the complex is disrupted
CC as temperatures rise. Phosphorylation of RshA decreases its interaction
CC with SigH, leading to increased SigH-mediated transcription.
CC {ECO:0000269|PubMed:14617153, ECO:0000269|PubMed:16298337,
CC ECO:0000269|PubMed:18728196, ECO:0000269|PubMed:22937074}.
CC -!- INDUCTION: Poorly expressed in exponential phase; induced by heat shock
CC (20-fold, 45 degrees Celsius). Induced 10-fold by the thiol-oxidative
CC agent diamide within 30 minutes of exposure, by 2 hours expression is
CC again normal. Autoregulates its own expression, part of the sigH-rshA
CC operon. {ECO:0000269|PubMed:10027986, ECO:0000269|PubMed:12123450}.
CC -!- DOMAIN: The sigma-70 factor domain-2 mediates sequence-specific
CC interaction with the -10 element in promoter DNA, and plays an
CC important role in melting the double-stranded DNA and the formation of
CC the transcription bubble. The sigma-70 factor domain-2 mediates
CC interaction with the RNA polymerase subunits RpoB and RpoC (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: The sigma-70 factor domain-4 contains a helix-turn-helix (H-T-
CC H) motif that mediates interaction with the -35 element in promoter
CC DNA. The domain also mediates interaction with the RNA polymerase
CC subunit RpoA. Interactions between sigma-70 factor domain-4 and anti-
CC sigma factors prevents interaction of sigma factors with the RNA
CC polymerase catalytic core.
CC -!- PTM: Phosphorylated, possibly on 2 residues, probably by PknB.
CC Phosphorylation of SigH has no effect on interaction with RshA.
CC {ECO:0000269|PubMed:18728196}.
CC -!- DISRUPTION PHENOTYPE: Increased susceptibility to oxidative stress
CC (H(2)O(2), cumene hydroperoxide and diamide, PubMed:12123450) and heat
CC shock (45 and 52 degrees Celsius). Loss of stress-induced expression of
CC a number of genes including clpB, dnaK, sigE and trxB
CC (PubMed:11567012), sigB and itself (PubMed:12123450). No effect on
CC infection of human derived macrophages, and murine J774.1 activated and
CC unactivated macrophages (PubMed:12123450).
CC {ECO:0000269|PubMed:11567012, ECO:0000269|PubMed:12123450}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the sigma-70 factor family. ECF subfamily.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46040.1; -; Genomic_DNA.
DR PIR; H70596; H70596.
DR RefSeq; NP_217739.1; NC_000962.3.
DR RefSeq; WP_003416897.1; NZ_NVQJ01000003.1.
DR PDB; 5ZX2; X-ray; 2.80 A; F=1-216.
DR PDB; 5ZX3; X-ray; 2.75 A; F=1-216.
DR PDB; 6JCX; X-ray; 2.90 A; F=1-216.
DR PDB; 6JCY; X-ray; 3.11 A; F=1-95, F=146-216.
DR PDB; 6KON; X-ray; 3.00 A; F=1-216.
DR PDB; 6KOO; X-ray; 2.80 A; F=1-216.
DR PDB; 6KOP; X-ray; 3.30 A; F=1-216.
DR PDB; 6KOQ; X-ray; 3.35 A; F=1-216.
DR PDBsum; 5ZX2; -.
DR PDBsum; 5ZX3; -.
DR PDBsum; 6JCX; -.
DR PDBsum; 6JCY; -.
DR PDBsum; 6KON; -.
DR PDBsum; 6KOO; -.
DR PDBsum; 6KOP; -.
DR PDBsum; 6KOQ; -.
DR AlphaFoldDB; P9WGH9; -.
DR SMR; P9WGH9; -.
DR IntAct; P9WGH9; 2.
DR STRING; 83332.Rv3223c; -.
DR PaxDb; P9WGH9; -.
DR DNASU; 888094; -.
DR GeneID; 888094; -.
DR KEGG; mtu:Rv3223c; -.
DR PATRIC; fig|83332.111.peg.3600; -.
DR TubercuList; Rv3223c; -.
DR eggNOG; COG1595; Bacteria.
DR OMA; NAKAWLF; -.
DR PhylomeDB; P9WGH9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0016987; F:sigma factor activity; IEA:UniProtKB-KW.
DR GO; GO:0034605; P:cellular response to heat; IMP:MTBBASE.
DR GO; GO:0006352; P:DNA-templated transcription, initiation; IEA:InterPro.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MTBBASE.
DR GO; GO:0009408; P:response to heat; IMP:MTBBASE.
DR GO; GO:0051409; P:response to nitrosative stress; IMP:MTBBASE.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MTBBASE.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR039425; RNA_pol_sigma-70-like.
DR InterPro; IPR014284; RNA_pol_sigma-70_dom.
DR InterPro; IPR014293; RNA_pol_sigma70_actinobac.
DR InterPro; IPR000838; RNA_pol_sigma70_ECF_CS.
DR InterPro; IPR007627; RNA_pol_sigma70_r2.
DR InterPro; IPR013249; RNA_pol_sigma70_r4_t2.
DR InterPro; IPR013325; RNA_pol_sigma_r2.
DR InterPro; IPR013324; RNA_pol_sigma_r3/r4-like.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR PANTHER; PTHR43133; PTHR43133; 1.
DR Pfam; PF04542; Sigma70_r2; 1.
DR Pfam; PF08281; Sigma70_r4_2; 1.
DR SUPFAM; SSF88659; SSF88659; 1.
DR SUPFAM; SSF88946; SSF88946; 1.
DR TIGRFAMs; TIGR02947; SigH_actino; 1.
DR TIGRFAMs; TIGR02937; sigma70-ECF; 1.
DR PROSITE; PS01063; SIGMA70_ECF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; DNA-binding; Phosphoprotein;
KW Reference proteome; Sigma factor; Stress response; Transcription;
KW Transcription regulation.
FT CHAIN 1..216
FT /note="ECF RNA polymerase sigma factor SigH"
FT /id="PRO_0000094004"
FT DNA_BIND 166..185
FT /note="H-T-H motif"
FT /evidence="ECO:0000250"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 37..99
FT /note="Sigma-70 factor domain-2"
FT REGION 140..191
FT /note="Sigma-70 factor domain-4"
FT MOTIF 56..59
FT /note="Polymerase core binding"
FT /evidence="ECO:0000255"
FT MUTAGEN 26
FT /note="T->A: No in vitro phosphorylation by PknB; when
FT associated with A-106."
FT /evidence="ECO:0000269|PubMed:18728196"
FT MUTAGEN 106
FT /note="T->A: No in vitro phosphorylation by PknB; when
FT associated with A-26."
FT /evidence="ECO:0000269|PubMed:18728196"
FT HELIX 23..48
FT /evidence="ECO:0007829|PDB:5ZX3"
FT HELIX 51..68
FT /evidence="ECO:0007829|PDB:5ZX3"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:5ZX3"
FT HELIX 80..99
FT /evidence="ECO:0007829|PDB:5ZX3"
FT STRAND 103..108
FT /evidence="ECO:0007829|PDB:5ZX3"
FT HELIX 111..119
FT /evidence="ECO:0007829|PDB:5ZX3"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:5ZX3"
FT HELIX 128..134
FT /evidence="ECO:0007829|PDB:5ZX3"
FT HELIX 141..147
FT /evidence="ECO:0007829|PDB:5ZX3"
FT HELIX 150..159
FT /evidence="ECO:0007829|PDB:5ZX3"
FT HELIX 166..172
FT /evidence="ECO:0007829|PDB:5ZX3"
FT HELIX 177..194
FT /evidence="ECO:0007829|PDB:5ZX3"
FT HELIX 198..201
FT /evidence="ECO:0007829|PDB:6KOO"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:6JCX"
SQ SEQUENCE 216 AA; 24225 MW; AC0C33B47DB40CFD CRC64;
MADIDGVTGS AGLQPGPSEE TDEELTARFE RDAIPLLDQL YGGALRMTRN PADAEDLLQE
TMVKAYAGFR SFRHGTNLKA WLYRILTNTY INSYRKKQRQ PAEYPTEQIT DWQLASNAEH
SSTGLRSAEV EALEALPDTE IKEALQALPE EFRMAVYYAD VEGFPYKEIA EIMDTPIGTV
MSRLHRGRRQ LRGLLADVAR DRGFARGEQA HEGVSS
