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Entry version 38 (07 Apr 2021)
Sequence version 1 (16 Apr 2014)
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Redox- and pH-responsive transcriptional regulator WhiB3



Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

A redox-sensitive transcriptional regulator. Maintains intracellular redox homeostasis by regulating catabolic metabolism and polyketide biosynthesis (PubMed:17609386, PubMed:19680450).

Regulates expression of the redox buffer ergothioneine (ERG) in a carbon-source-dependent manner; loss of ERG or mycothiol (MSH, the other major redox buffer in this bacteria) leads to respiratory alterations and bioenergetic deficiencies that negatively impact virulence (PubMed:26774486).

In response to low external pH (like that found in host macrophage phagosomes) alters endogenous gene expression leading to acid resistance; MSH and WhiB3 are probably part of a regulatory circuit that mediates gene expression upon acid stress (PubMed:26637353).

Regulates pathogenic lipid synthesis, coordinating proprionate flux (and other host-derived fatty acid oxidation intermediates) into methyl-branched fatty acids (polyacyltrehalose, phthiocerol dimycocerosates, sulfolipids) and the storage lipid triacylglycerol, functioning as reductive sink (PubMed:19680450).

During intracellular growth M.tuberculosis uses host fatty acids as an energy source, generating large quantities of proprionate and NADH/NADPH, which are toxic and highly reducing respectively. WhiB3 is thought to help dissipate proprionate and NADH/NADPH by switching to the in vivo carbon source and via lipid anabolism (PubMed:19680450).

Responds to NO and O2 (PubMed:17609386).

Regulates expression of genes encoding modular polyketide synthases such as pks2, pks3 and fbpA (PubMed:19680450).

The oxidized apo-form of WhiB3 binds DNA (with 2 intramolecular disulfide bonds); holo-WhiB3 (with the 4Fe-4S cluster) binds DNA considerably less well (PubMed:19680450).

Discriminates poorly between specific and non-specific DNA-binding. Plays a role in virulence and nutritional stress (PubMed:11880648, PubMed:17609386, PubMed:26637353).

In its apo-form can act as a protein disulfide reductase (PubMed:18550384).

7 Publications

May respond to mycothiol (MSH) redox potential (E-MSH) which decreases at pH 4.5 for up to 72 hours, indicative of cellular reductive stress; deletion of whiB3 leads to a lesser E-MSH at 72 hours, indicative of cellular oxidative stress (PubMed:26637353).

Probably via its effects on production of polyketide lipids, regulates host gene expression, leading to blockage of phagosome maturation (PubMed:26637353).

Equilibration of extra- and intracytoplasmic pH kills bacteria (PubMed:26637353).

1 Publication

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

[4Fe-4S] cluster3 PublicationsNote: Binds 1 [4Fe-4S] cluster per subunit (PubMed:17609386). Following nitrosylation of the [4Fe-4S] cluster binds 1 [4Fe-8(NO)] cluster per subunit (PubMed:17609386).3 Publications


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi23Dinitrosyliron [4Fe-8(NO)]; alternate1 Publication1
Metal bindingi23Iron-sulfur (4Fe-4S); alternate1 Publication1
Metal bindingi53Dinitrosyliron [4Fe-8(NO)]; alternate1 Publication1
Metal bindingi53Iron-sulfur (4Fe-4S); alternate1 Publication1
Metal bindingi56Dinitrosyliron [4Fe-8(NO)]; alternate1 Publication1
Metal bindingi56Iron-sulfur (4Fe-4S); alternate1 Publication1
Metal bindingi62Dinitrosyliron [4Fe-8(NO)]; alternate1 Publication1
Metal bindingi62Iron-sulfur (4Fe-4S); alternate1 Publication1

<p>The <a href="">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionDNA-binding
Biological processStress response, Transcription, Transcription regulation, Virulence
Ligand4Fe-4S, Iron, Iron-sulfur, Metal-binding

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Redox- and pH-responsive transcriptional regulator WhiB3
<p>This subsection of the <a href="">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Ordered Locus Names:Rv3416
<p>This subsection of the <a href="">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
<p>This subsection of the <a href="">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri83332 [NCBI]
<p>This subsection of the <a href="">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
<p>This subsection of the <a href="">Names and taxonomy</a> section is present for entries that are part of a <a href="">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000001584 <p>A UniProt <a href="">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome

Organism-specific databases

Mycobacterium tuberculosis strain H37Rv genome database


<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti


<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

Not essential for growth in culture, or growth in vivo in mouse and guinea pig infections (PubMed:11880648). Disruption significantly enhances survival of immunocompetent mice (PubMed:11880648). Decreased bacterial growth in guinea pig lungs, but not spleen (PubMed:26637353). Growth on minimal media, glucose or succinate is poor, suggesting WhiB3 is involved in starvation response (PubMed:17609386). Growth on acetate is better than wild-type (PubMed:17609386). 55-fold decreased survival at pH 4.5, no difference at pH 5.5 or 6.6 (PubMed:26637353). Altered expression of genes involved in cell wall lipid composition, the ESX-1 secretion system and redox balance, impairs the mycothiol-specific reductive response to acid stress (PubMed:26637353). Dysfunctional respiration when grown in pyruvate, increased intracellular ergothioneine (ERG) production when grown in a number of carbon sources (PubMed:26774486). Upon infection of human THP-1 macrophage-like cells bacteria are localized to acidified lysosomes (M.tuberculosis usually blocks lysosome acidification), do not reduce mycothiol (MSH) and have significantly decreased survival (PubMed:26637353). Leads to up-regulation of host innate immunity genes usually repressed by M.tuberculosis (such as phagosome maturation and TLR signaling) and down-regulation of genes that inhibit autophagy (such as mTOR) (PubMed:26637353). Cell size, shape and surface architecture are perturbed, as is synthesis of cell surface associated virulence lipids both in culture and in cultured macrophages, or in response to oxidizing or reducing agents (PubMed:19680450). Disrupted strains are more resistant to toxic levels of propionate (PubMed:19680450).5 Publications


Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi23C → A: No 4Fe-4S cluster assembly, does not complement growth defects; when associated with A-53; A-56 and A-62. 1 Publication1
Mutagenesisi53C → A: No 4Fe-4S cluster assembly, does not complement growth defects; when associated with A-23; A-56 and A-62. 1 Publication1
Mutagenesisi56C → A: No 4Fe-4S cluster assembly, does not complement growth defects; when associated with A-33; A-53 and A-62. 1 Publication1
Mutagenesisi62C → A: No 4Fe-4S cluster assembly, does not complement growth defects; when associated with A-33; A-53 and A-56. 1 Publication1

Miscellaneous databases

Pathogen-Host Interaction database


<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00004203821 – 102Redox- and pH-responsive transcriptional regulator WhiB3Add BLAST102

<p>This subsection of the <a href="">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

The 4Fe-4S cluster interacts with NO, forming a protein-bound dinitrosyliron dithiol complex (PubMed:17609386).1 Publication
The 4Fe-4S cluster interacts with O2, leading to its degradation. Cluster loss takes about 2 hours (PubMed:17609386). Once in the apo-form the cysteines oxidize to form 2 intramolecular disulfide bonds (PubMed:18550384).2 Publications

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDb, a database of protein abundance averages across all three domains of life


<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

100-fold induced in wild-type C57BL/6 mice 2 weeks after lung infection, RNA levels drop to 30X induced 8 weeks post-infection (PubMed:16923787). Similar but less dramatic induction is seen in immunocompromised mice (PubMed:16923787). Rapidly induced in resting mouse macrophages, remains up-regulated for at least 60 hours, continuing induction is repressed by interferon gamma (PubMed:16923787). Induced by growth at acidic pH (PubMed:26637353).2 Publications

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer (Probable) (PubMed:18550384).

Interacts with the C-terminal 54 residues of sigma factor SigA (RpoV) (PubMed:11880648).

1 Publication1 Publication

<p>This subsection of the '<a href="">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="">IntAct database</a>. It is updated at every <a href="">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Protein-protein interaction databases

Protein interaction database and analysis system

P9WF41, 1 interactor

STRING: functional protein association networks


<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models


Database of comparative protein structure models


<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini22 – 864Fe-4S Wbl-typeAdd BLAST65

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the WhiB family.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

ENOG5032S23, Bacteria

Identification of Orthologs from Complete Genome Data


Database for complete collections of gene phylogenies


Family and domain databases

HAMAP database of protein families

MF_01479, WhiB, 1 hit

Integrated resource of protein families, domains and functional sites

View protein in InterPro
IPR034768, 4FE4S_WBL
IPR003482, Whib

The PANTHER Classification System

PTHR38839, PTHR38839, 1 hit

Pfam protein domain database

View protein in Pfam
PF02467, Whib, 1 hit

PROSITE; a protein domain and family database

View protein in PROSITE
PS51674, 4FE4S_WBL, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="">length</a> and <a href="">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="">Sequence</a> section indicates if the <a href="">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

P9WF41-1 [UniParc]FASTAAdd to basket
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Mass (Da):11,612
Last modified:April 16, 2014 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iC38A6774457F71BA

<p>This subsection of the 'Sequence' section reports information derived from mass spectrometry experiments done on the entire protein or on biologically active derived peptide(s).<p><a href='/help/mass_spectrometry' target='_top'>More...</a></p>Mass spectrometryi

Molecular mass is 14636.76 Da. Determined by MALDI. Fully reduced protein.1 Publication
Molecular mass is 14407.22 Da. Determined by MALDI. Fully oxidized protein.1 Publication

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database


GenBank nucleotide sequence database


DNA Data Bank of Japan; a nucleotide sequence database

Links Updated
AL123456 Genomic DNA Translation: CCP46238.1

Protein sequence database of the Protein Information Resource


NCBI Reference Sequences

NP_217933.1, NC_000962.3
WP_003418017.1, NZ_NVQJ01000027.1

Genome annotation databases

Database of genes from NCBI RefSeq genomes


KEGG: Kyoto Encyclopedia of Genes and Genomes


<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
Links Updated
AL123456 Genomic DNA Translation: CCP46238.1
RefSeqiNP_217933.1, NC_000962.3
WP_003418017.1, NZ_NVQJ01000027.1

3D structure databases


Protein-protein interaction databases

IntActiP9WF41, 1 interactor

Proteomic databases


Genome annotation databases


Organism-specific databases


Phylogenomic databases

eggNOGiENOG5032S23, Bacteria

Miscellaneous databases


Family and domain databases

HAMAPiMF_01479, WhiB, 1 hit
InterProiView protein in InterPro
IPR034768, 4FE4S_WBL
IPR003482, Whib
PANTHERiPTHR38839, PTHR38839, 1 hit
PfamiView protein in Pfam
PF02467, Whib, 1 hit
PROSITEiView protein in PROSITE
PS51674, 4FE4S_WBL, 1 hit

MobiDB: a database of protein disorder and mobility annotations


<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiWHIB3_MYCTU
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P9WF41
Secondary accession number(s): F2GEG1
, L0TCG8, Q50710, Q7D5K3
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: April 16, 2014
Last modified: April 7, 2021
This is version 38 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Reference proteome


  1. SIMILARITY comments
    Index of protein domains and families
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