WHIB4_MYCTU
ID WHIB4_MYCTU Reviewed; 118 AA.
AC P9WF39; F2GFC4; L0TGF3; O69649; Q7D530;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Transcriptional regulator WhiB4;
GN Name=whiB4; OrderedLocusNames=Rv3681c;
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, SUBUNIT, MASS
RP SPECTROMETRY, DISULFIDE BONDS, AND MUTAGENESIS OF CYS-37; CYS-59; CYS-62
RP AND CYS-68.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17302817; DOI=10.1111/j.1365-2958.2007.05589.x;
RA Alam M.S., Garg S.K., Agrawal P.;
RT "Molecular function of WhiB4/Rv3681c of Mycobacterium tuberculosis H37Rv: a
RT [4Fe-4S] cluster co-ordinating protein disulphide reductase.";
RL Mol. Microbiol. 63:1414-1431(2007).
RN [3]
RP FUNCTION, COFACTOR, AND 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 [4]
RP FUNCTION IN TRANSCRIPTION, COFACTOR, DINITROSYLATION, SUBUNIT, DNA-BINDING,
RP DISULFIDE BOND, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-37; CYS-59;
RP CYS-62 AND CYS-68.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22780904; DOI=10.1111/j.1365-2958.2012.08165.x;
RA Chawla M., Parikh P., Saxena A., Munshi M., Mehta M., Mai D.,
RA Srivastava A.K., Narasimhulu K.V., Redding K.E., Vashi N., Kumar D.,
RA Steyn A.J., Singh A.;
RT "Mycobacterium tuberculosis WhiB4 regulates oxidative stress response to
RT modulate survival and dissemination in vivo.";
RL Mol. Microbiol. 85:1148-1165(2012).
CC -!- FUNCTION: Redox-responsive transcriptional regulator that regulates a
CC set of genes involved in protection against environmental stresses
CC encountered during infection. The loss of the O(2) and NO-responsive
CC 4Fe-4S cluster and subsequent redox modifications of Cys residue thiols
CC (possibly by disulfide bond formation) may activate its role in gene
CC regulation. The thiol-oxidized apo-form binds in a sequence non-
CC specific manner to GC-rich DNA, probably in the minor groove. Represses
CC transcription of a number of genes including itself. The reduced apo-
CC form and holo-form do not bind DNA. The apo-form can act as protein
CC disulfide reductase. {ECO:0000269|PubMed:17302817,
CC ECO:0000269|PubMed:19016840, ECO:0000269|PubMed:22780904}.
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:17302817, ECO:0000269|PubMed:19016840,
CC ECO:0000269|PubMed:22780904};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. The cluster responds to both
CC O(2) and NO. Following nitrosylation of the [4Fe-4S] cluster binds 1
CC [4Fe-8(NO)] cluster per subunit. {ECO:0000269|PubMed:17302817,
CC ECO:0000269|PubMed:19016840, ECO:0000269|PubMed:22780904};
CC -!- SUBUNIT: Homodimer in the presence of reducing agents
CC (PubMed:17302817); the oxidized apo-form makes dimers and trimers while
CC the redeced apo-form does not (PubMed:22780904). Upon over expression
CC in aerobically grown M.smegmatis, apo-WhiB4 forms trimers held together
CC by disulfide bonds. {ECO:0000269|PubMed:17302817,
CC ECO:0000269|PubMed:22780904}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- PTM: The 4Fe-4S cluster is very sensitive to air, degrading from 4Fe-4S
CC via 3Fe-3S to 2Fe-2S then cluster loss. Upon cluster removal
CC intramolecular disulfide bonds are formed.
CC -!- PTM: Can be nitrosylated by NO, leading to the formation of a tetrakis-
CC cysteinyl [Fe4-(NO)8] complex.
CC -!- MASS SPECTROMETRY: Mass=18047.83; Method=MALDI; Note=Fully oxidized
CC recombinant protein tagged at both termini.;
CC Evidence={ECO:0000269|PubMed:17302817};
CC -!- MASS SPECTROMETRY: Mass=18275.18; Method=MALDI; Note=Fully reduced
CC recombinant protein tagged at both termini.;
CC Evidence={ECO:0000269|PubMed:17302817};
CC -!- DISRUPTION PHENOTYPE: During aerobic growth in culture grows more
CC slowly over the whole life cycle, a 2X reduced ratio of NAD(+)/NADH
CC (reflects redox metabolism) and a 1.5X reduction in membrane potential.
CC Has increased resistance to oxidative stress. Enhanced growth in
CC uninduced and activated macrophages, as well as enhanced growth at
CC reduced O(2) tension. However reduced survival in guinea pig spleen but
CC not lungs following aerosol infection. A number of genes are induced,
CC including whiB4, whiB6, genes involved in antioxidant systems, redox
CC factor PQQ and several members of the PE-PPE family.
CC {ECO:0000269|PubMed:22780904}.
CC -!- SIMILARITY: Belongs to the WhiB family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46505.1; -; Genomic_DNA.
DR PIR; B70791; B70791.
DR RefSeq; NP_218198.2; NC_000962.3.
DR RefSeq; WP_003419743.1; NZ_NVQJ01000028.1.
DR PDB; 7F7N; NMR; -; A=1-118.
DR PDBsum; 7F7N; -.
DR AlphaFoldDB; P9WF39; -.
DR SMR; P9WF39; -.
DR STRING; 83332.Rv3681c; -.
DR PaxDb; P9WF39; -.
DR GeneID; 45427677; -.
DR GeneID; 885320; -.
DR KEGG; mtu:Rv3681c; -.
DR TubercuList; Rv3681c; -.
DR eggNOG; ENOG5032TCV; Bacteria.
DR OMA; FAAQRKH; -.
DR PhylomeDB; P9WF39; -.
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; IDA:MTBBASE.
DR GO; GO:0035731; F:dinitrosyl-iron complex binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003677; F:DNA binding; IDA:MTBBASE.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0047134; F:protein-disulfide reductase (NAD(P)) activity; IDA:MTBBASE.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IBA:GO_Central.
DR HAMAP; MF_01479; WhiB; 1.
DR InterPro; IPR034768; 4FE4S_WBL.
DR InterPro; IPR003482; Whib.
DR PANTHER; PTHR38839; PTHR38839; 1.
DR Pfam; PF02467; Whib; 1.
DR PROSITE; PS51674; 4FE4S_WBL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Cytoplasm; Disulfide bond; DNA-binding; Iron;
KW Iron-sulfur; Metal-binding; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..118
FT /note="Transcriptional regulator WhiB4"
FT /id="PRO_0000420383"
FT DOMAIN 36..92
FT /note="4Fe-4S Wbl-type"
FT BINDING 37
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000305"
FT BINDING 59
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000305"
FT BINDING 62
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000305"
FT BINDING 68
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000305"
FT DISULFID 37..68
FT /note="Upon loss of 4Fe-S clusters"
FT /evidence="ECO:0000305"
FT DISULFID 59..62
FT /note="Upon loss of 4Fe-S clusters"
FT /evidence="ECO:0000305"
FT MUTAGEN 37
FT /note="C->A: Apo-form does not bind DNA."
FT /evidence="ECO:0000269|PubMed:17302817,
FT ECO:0000269|PubMed:22780904"
FT MUTAGEN 37
FT /note="C->S: Partial loss of the Fe-S center. Complete loss
FT of center and of disulfide reductase; when associated with
FT S-59; S-62 and S-68."
FT /evidence="ECO:0000269|PubMed:17302817,
FT ECO:0000269|PubMed:22780904"
FT MUTAGEN 59
FT /note="C->A: Apo-form does not bind DNA."
FT /evidence="ECO:0000269|PubMed:17302817,
FT ECO:0000269|PubMed:22780904"
FT MUTAGEN 59
FT /note="C->S: Partial loss of the Fe-S center. Complete loss
FT of center and of disulfide reductase; when associated with
FT S-37; S-62 and S-68."
FT /evidence="ECO:0000269|PubMed:17302817,
FT ECO:0000269|PubMed:22780904"
FT MUTAGEN 62
FT /note="C->A: Apo-form does not bind DNA."
FT /evidence="ECO:0000269|PubMed:17302817,
FT ECO:0000269|PubMed:22780904"
FT MUTAGEN 62
FT /note="C->S: Partial loss of the Fe-S center. Complete loss
FT of center and of disulfide reductase; when associated with
FT S-37; S-59 and S-68."
FT /evidence="ECO:0000269|PubMed:17302817,
FT ECO:0000269|PubMed:22780904"
FT MUTAGEN 68
FT /note="C->A: Apo-form does not bind DNA."
FT /evidence="ECO:0000269|PubMed:17302817,
FT ECO:0000269|PubMed:22780904"
FT MUTAGEN 68
FT /note="C->S: Partial loss of the Fe-S center. Complete loss
FT of center and of disulfide reductase; when associated with
FT S-37; S-59 and S-62."
FT /evidence="ECO:0000269|PubMed:17302817,
FT ECO:0000269|PubMed:22780904"
FT HELIX 24..30
FT /evidence="ECO:0007829|PDB:7F7N"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:7F7N"
FT TURN 42..44
FT /evidence="ECO:0007829|PDB:7F7N"
FT HELIX 45..48
FT /evidence="ECO:0007829|PDB:7F7N"
FT HELIX 54..58
FT /evidence="ECO:0007829|PDB:7F7N"
FT TURN 67..72
FT /evidence="ECO:0007829|PDB:7F7N"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:7F7N"
FT HELIX 87..96
FT /evidence="ECO:0007829|PDB:7F7N"
FT HELIX 101..112
FT /evidence="ECO:0007829|PDB:7F7N"
SQ SEQUENCE 118 AA; 13211 MW; 6E6451A2714B859B CRC64;
MSGTRPAARR TNLTAAQNVV RSVDAEERIA WVSKALCRTT DPDELFVRGA AQRKAAVICR
HCPVMQECAA DALDNKVEFG VWGGMTERQR RALLKQHPEV VSWSDYLEKR KRRTGTAG
