Function

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 O(2) (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). {ECO:0000269|PubMed:11880648, ECO:0000269|PubMed:17609386, ECO:0000269|PubMed:18550384, ECO:0000269|PubMed:19016840, ECO:0000269|PubMed:19680450, ECO:0000269|PubMed:26637353, ECO:0000269|PubMed:26774486}.; FUNCTION: 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). {ECO:0000269|PubMed:26637353}.

Family

WhiB family

GO

• regulation of lipid metabolic process GO:0019216 biological_process
• metal ion binding GO:0046872 molecular_function
• Actinobacterium-type cell wall biogenesis GO:0071766 biological_process
• pathogenesis GO:0009405 biological_process
• protein disulfide oxidoreductase activity GO:0015035 molecular_function
• cell wall GO:0005618 cellular_component
• DNA binding GO:0003677 molecular_function
• negative regulation of transcription, DNA-templated GO:0045892 biological_process
• cytoplasm GO:0005737 cellular_component
• protein-disulfide reductase activity GO:0047134 molecular_function
• iron-sulfur cluster binding GO:0051536 molecular_function
• 4 iron, 4 sulfur cluster binding GO:0051539 molecular_function
• dinitrosyl-iron complex binding GO:0035731 molecular_function
• cell redox homeostasis GO:0045454 biological_process

InterPro

• IPR003482
• IPR034768

UniProt

P9WF41

GenBank

Rv3416

EnsemblBacteria

Rv3416

Mycobrowser

Rv3416

Rv3416 doesn't seem to be a targeted by any drug.

Rv3416 doesn't seem to be involved in any pathway.