RPSC_MYCTU
ID RPSC_MYCTU Reviewed; 185 AA.
AC P9WGH1; L0T8P5; P66809; Q10679;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 42.
DE RecName: Full=ECF RNA polymerase sigma factor SigC;
DE Short=ECF sigma factor SigC;
DE AltName: Full=Alternative RNA polymerase sigma factor SigC;
DE AltName: Full=RNA polymerase sigma-C factor;
DE Short=Sigma-C factor;
GN Name=sigC; OrderedLocusNames=Rv2069; ORFNames=MTCY49.08;
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 INDUCTION.
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 [3]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16735723; DOI=10.1099/mic.0.28591-0;
RA Karls R.K., Guarner J., McMurray D.N., Birkness K.A., Quinn F.D.;
RT "Examination of Mycobacterium tuberculosis sigma factor mutants using low-
RT dose aerosol infection of guinea pigs suggests a role for SigC in
RT pathogenesis.";
RL Microbiology 152:1591-1600(2006).
RN [4]
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 [5]
RP START SITE CONFIRMATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19118359; DOI=10.1099/mic.0.022889-0;
RA Smollett K.L., Fivian-Hughes A.S., Smith J.E., Chang A., Rao T.,
RA Davis E.O.;
RT "Experimental determination of translational start sites resolves
RT uncertainties in genomic open reading frame predictions - application to
RT Mycobacterium tuberculosis.";
RL Microbiology 155:186-197(2009).
RN [6]
RP REGULATION, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22015173; DOI=10.1016/j.tube.2011.09.005;
RA Chang A., Smollett K.L., Gopaul K.K., Chan B.H., Davis E.O.;
RT "Mycobacterium tuberculosis H37Rv sigC is expressed from two promoters but
RT is not auto-regulatory.";
RL Tuberculosis 92:48-55(2012).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-112, X-RAY CRYSTALLOGRAPHY (3.0
RP ANGSTROMS) OF 117-185, REGULATION MODEL, AND MUTAGENESIS OF TRP-38 AND
RP TRP-77.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17145760; DOI=10.1074/jbc.m606283200;
RA Thakur K.G., Joshi A.M., Gopal B.;
RT "Structural and biophysical studies on two promoter recognition domains of
RT the extra-cytoplasmic function sigma factor sigma(C) from Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 282:4711-4718(2007).
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 usually
CC held in an inactive form by an anti-sigma factor until released by
CC regulated intramembrane proteolysis; this sigma factor does not seem to
CC have a cognate anti-sigma factor however. It has been suggested that
CC the sigma domains 2 and 4 may interact via polar residues in this
CC protein to autoregulate. Positively regulates expression of a small
CC regulon of genes.
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. {ECO:0000250}.
CC -!- INDUCTION: The most abundant of the sigma factor transcripts, it is
CC expressed in exponential phase; repressed by detergent (7-fold), heat
CC shock (9-fold, 45 degrees Celsius) and in stationary phase. Not
CC autoregulated (PubMed:22015173). {ECO:0000269|PubMed:10027986,
CC ECO:0000269|PubMed:22015173}.
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 (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: No effect on growth in culture, or in isolated
CC macrophages; infected guinea pigs have a highly attenuated infection
CC with few granulomas and no necrotic centers.
CC {ECO:0000269|PubMed:16735723, ECO:0000269|PubMed:22015173}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the sigma-70 factor family. ECF subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: The protein has been shown to be 126 residues longer
CC (PubMed:17145760), but in (PubMed:19118359) no evidence of this longer
CC protein was seen. {ECO:0000305|PubMed:17145760,
CC ECO:0000305|PubMed:19118359}.
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DR EMBL; AL123456; CCP44843.1; -; Genomic_DNA.
DR PIR; H70764; H70764.
DR RefSeq; NP_216585.1; NC_000962.3.
DR RefSeq; WP_003410678.1; NZ_NVQJ01000047.1.
DR PDB; 2O7G; X-ray; 2.70 A; A/B=1-112.
DR PDB; 2O8X; X-ray; 3.00 A; A/B/C=117-185.
DR PDBsum; 2O7G; -.
DR PDBsum; 2O8X; -.
DR AlphaFoldDB; P9WGH1; -.
DR SMR; P9WGH1; -.
DR STRING; 83332.Rv2069; -.
DR PaxDb; P9WGH1; -.
DR GeneID; 888723; -.
DR KEGG; mtu:Rv2069; -.
DR TubercuList; Rv2069; -.
DR eggNOG; COG1595; Bacteria.
DR OMA; NWNSFRK; -.
DR PhylomeDB; P9WGH1; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0016987; F:sigma factor activity; IEA:UniProtKB-KW.
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; IEP:MTBBASE.
DR GO; GO:0001666; P:response to hypoxia; IEP:MTBBASE.
DR GO; GO:0009415; P:response to water; IEP:MTBBASE.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP: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; 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; TIGR02937; sigma70-ECF; 1.
DR PROSITE; PS01063; SIGMA70_ECF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Reference proteome; Sigma factor; Transcription;
KW Transcription regulation.
FT CHAIN 1..185
FT /note="ECF RNA polymerase sigma factor SigC"
FT /id="PRO_0000094021"
FT DNA_BIND 149..168
FT /note="H-T-H motif"
FT /evidence="ECO:0000250"
FT REGION 30..94
FT /note="Sigma-70 factor domain-2"
FT REGION 123..174
FT /note="Sigma-70 factor domain-4"
FT MOTIF 52..55
FT /note="Polymerase core binding"
FT /evidence="ECO:0000255"
FT MUTAGEN 38
FT /note="W->A: Blue shift in fluorescence emission, possible
FT decrease in -10 promoter recognition."
FT /evidence="ECO:0000269|PubMed:17145760"
FT MUTAGEN 77
FT /note="W->A: Red shift in fluorescence emission."
FT /evidence="ECO:0000269|PubMed:17145760"
FT HELIX 5..19
FT /evidence="ECO:0007829|PDB:2O7G"
FT HELIX 23..44
FT /evidence="ECO:0007829|PDB:2O7G"
FT HELIX 47..64
FT /evidence="ECO:0007829|PDB:2O7G"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:2O7G"
FT HELIX 74..89
FT /evidence="ECO:0007829|PDB:2O7G"
FT HELIX 118..125
FT /evidence="ECO:0007829|PDB:2O8X"
FT TURN 126..129
FT /evidence="ECO:0007829|PDB:2O8X"
FT HELIX 133..143
FT /evidence="ECO:0007829|PDB:2O8X"
FT HELIX 149..156
FT /evidence="ECO:0007829|PDB:2O8X"
FT HELIX 160..175
FT /evidence="ECO:0007829|PDB:2O8X"
SQ SEQUENCE 185 AA; 19966 MW; FF839B4279929917 CRC64;
MTATASDDEA VTALALSAAK GNGRALEAFI KATQQDVWRF VAYLSDVGSA DDLTQETFLR
AIGAIPRFSA RSSARTWLLA IARHVVADHI RHVRSRPRTT RGARPEHLID GDRHARGFED
LVEVTTMIAD LTTDQREALL LTQLLGLSYA DAAAVCGCPV GTIRSRVARA RDALLADAEP
DDLTG
