WHB5A_MYCTU
ID WHB5A_MYCTU Reviewed; 139 AA.
AC P71592; F2GPM6; L0T257;
DT 28-NOV-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Transcriptional regulator WhiB5;
GN Name=whiB5; OrderedLocusNames=Rv0022c;
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 FUNCTION AS A PROTEIN DISULFIDE REDUCTASE, COFACTOR, MASS SPECTROMETRY, AND
RP DISULFIDE BOND.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19016840; DOI=10.1111/j.1742-4658.2008.06755.x;
RA Alam M.S., Garg S.K., Agrawal P.;
RT "Studies on structural and functional divergence among seven WhiB proteins
RT of Mycobacterium tuberculosis H37Rv.";
RL FEBS J. 276:76-93(2009).
RN [3]
RP FUNCTION IN TRANSCRIPTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22733573; DOI=10.1128/iai.06328-11;
RA Casonato S., Cervantes Sanchez A., Haruki H., Rengifo Gonzalez M.,
RA Provvedi R., Dainese E., Jaouen T., Gola S., Bini E., Vicente M.,
RA Johnsson K., Ghisotti D., Palu G., Hernandez-Pando R., Manganelli R.;
RT "WhiB5, a transcriptional regulator that contributes to Mycobacterium
RT tuberculosis virulence and reactivation.";
RL Infect. Immun. 80:3132-3144(2012).
CC -!- FUNCTION: A transcription factor that is probably redox-responsive.
CC Probably plays a role in immunomodulation and reactivation after
CC chronic infection. Its induction results in transcription of a number
CC of genes including sigM, and the genes for 2 type VII secretion systems
CC ESX-2 and ESX-4. Seems to negatively regulate its own expression. The
CC apo-form has been shown to act as a protein disulfide reductase. The
CC apo- but not holo-form probably binds DNA.
CC {ECO:0000269|PubMed:19016840, ECO:0000269|PubMed:22733573}.
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250, ECO:0000305};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. Contains 1 [2Fe-2S] cluster
CC after reconstitution of overexpressed protein from E.coli. Following
CC nitrosylation of the [4Fe-4S] cluster binds 1 [4Fe-8(NO)] cluster per
CC subunit. {ECO:0000250, ECO:0000305};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- INDUCTION: Maximal expression during progressive infection is between
CC 2-4 weeks, however low, stable expression during chronic infection.
CC {ECO:0000269|PubMed:22733573}.
CC -!- PTM: The Fe-S cluster can be nitrosylated by nitric oxide (NO).
CC {ECO:0000250}.
CC -!- PTM: Upon Fe-S cluster removal intramolecular disulfide bonds are
CC formed.
CC -!- MASS SPECTROMETRY: Mass=20733.50; Method=MALDI; Note=Fully oxidized
CC recombinant protein tagged at both termini.;
CC Evidence={ECO:0000269|PubMed:19016840};
CC -!- MASS SPECTROMETRY: Mass=20962.96; Method=MALDI; Note=Fully reduced
CC recombinant protein tagged at both termini.;
CC Evidence={ECO:0000269|PubMed:19016840};
CC -!- DISRUPTION PHENOTYPE: Not essential in culture. Gives an attenuated
CC infection during both progressive and chronic mouse infections. Mice
CC infected with the disrupted strain induce a stronger host immune
CC response than wild-type. Growth inhibited by S-nitrosoglutathione
CC (GSNO), a source of glutathione and nitric oxide. Mutant cells are less
CC metabolically active. When chronic infection was reactivated by
CC corticosterone the mutant strain was not able to resume growth,
CC suggesting that WhiB5 might be involved with bacillary proliferation
CC during reactivation. {ECO:0000269|PubMed:22733573}.
CC -!- SIMILARITY: Belongs to the WhiB family. {ECO:0000305}.
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DR EMBL; AL123456; CCP42744.1; -; Genomic_DNA.
DR PIR; D70700; D70700.
DR RefSeq; NP_214536.1; NC_000962.3.
DR RefSeq; WP_003400388.1; NZ_NVQJ01000005.1.
DR AlphaFoldDB; P71592; -.
DR SMR; P71592; -.
DR STRING; 83332.Rv0022c; -.
DR PaxDb; P71592; -.
DR DNASU; 887071; -.
DR GeneID; 45423982; -.
DR GeneID; 887071; -.
DR KEGG; mtu:Rv0022c; -.
DR TubercuList; Rv0022c; -.
DR eggNOG; ENOG5031JMD; Bacteria.
DR OMA; EEYGVWA; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-UniRule.
DR GO; GO:0035731; F:dinitrosyl-iron complex binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-UniRule.
DR HAMAP; MF_01479; WhiB; 1.
DR InterPro; IPR034768; 4FE4S_WBL.
DR InterPro; IPR003482; Whib.
DR Pfam; PF02467; Whib; 1.
DR PROSITE; PS51674; 4FE4S_WBL; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Activator; Cytoplasm; Disulfide bond; DNA-binding; Iron;
KW Iron-sulfur; Metal-binding; Reference proteome; Transcription;
KW Transcription regulation; Virulence.
FT CHAIN 1..139
FT /note="Transcriptional regulator WhiB5"
FT /id="PRO_0000420384"
FT DOMAIN 4..77
FT /note="4Fe-4S Wbl-type"
FT BINDING 5
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 41
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 45
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 53
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
SQ SEQUENCE 139 AA; 15178 MW; C4AFADECFC9DFDD2 CRC64;
MAHPCATDPE LWFGYPDDDG SDGAAKARAY ERSATQARIQ CLRRCPLLQQ RRCAQHAVEH
RVEYGVWAGI KLPGGQYRKR EQLAAAHDVL RRIAGGEINS RQLPDNAALL ARNEGLEVTP
VPGVVVHLPI AQVGPQPAA
