UniProt functional annotation for O31602



	UniProt functional annotation for O31602

UniProt code: O31602.

Organism: Bacillus subtilis (strain 168).

Taxonomy: Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.

Function: Global transcriptional regulator that plays a key role in stress response and exerts either positive or negative regulation of genes (PubMed:12642660, PubMed:15659166, PubMed:16885442, PubMed:18662407, PubMed:18687074, PubMed:29271514). Acts by interacting with the C-terminal domain of the alpha subunit of the RNA polymerase (RNAP) (PubMed:12642660, PubMed:15659166, PubMed:18687074, PubMed:20084284). This interaction can enhance binding of RNAP to the promoter region of target genes and stimulate their transcription, or block interaction of RNAP with activator proteins and repress transcription (PubMed:12642660, PubMed:15659166, PubMed:18687074, PubMed:20084284). Exhibits no DNA-binding activity (PubMed:15659166, PubMed:18687074). {ECO:0000269|PubMed:12642660, ECO:0000269|PubMed:15659166, ECO:0000269|PubMed:16885442, ECO:0000269|PubMed:18662407, ECO:0000269|PubMed:18687074, ECO:0000269|PubMed:20084284, ECO:0000269|PubMed:29271514}.

Function: Induces the expression of a large number of genes in response to a variety of stress conditions, such as disulfide, heat and cell wall stress, while concurrently repressing transcription of genes involved in various developmental and growth-related pathways during periods of extreme stress (PubMed:12642660, PubMed:14597697). Functions in the oxidative stress response via induction of the transcription of thioredoxin (trxA) and thioredoxin reductase (trxB) during thiol- specific oxidative (disulfide) stress (PubMed:14597697, PubMed:15659166, PubMed:18687074). Mediates response to oxidative stress caused by paraquat (PQ) via induction of the methionine sulfoxide reductase genes, msrA and msrB (PubMed:18662407). Also acts as a transcriptional activator of the bacillithiol (BSH) biosynthesis genes in response to oxidizing conditions and thio-reactive compounds (PubMed:23894131). Involved in heat stress response and thermotolerance development, which results in diminished cellular protein aggregates (PubMed:24417481). Plays an important adaptive role in the cell wall stress response (PubMed:29271514). Participates in sulfate-dependent control of organosulfur metabolism. Negatively controls, via CymR, the expression of the organosulfur utilization operons ytmI, yxeI and ssu, and directly activates yrrT operon expression during growth in medium containing methionine as sole sulfur source (PubMed:16885442). Negatively affects competence and sporulation (PubMed:11703662, PubMed:12028382). Inhibits biofilm formation in response to disulfide stress by repressing biofilm matrix genes (PubMed:30718304). {ECO:0000269|PubMed:11703662, ECO:0000269|PubMed:12028382, ECO:0000269|PubMed:12642660, ECO:0000269|PubMed:14597697, ECO:0000269|PubMed:15659166, ECO:0000269|PubMed:16885442, ECO:0000269|PubMed:18662407, ECO:0000269|PubMed:18687074, ECO:0000269|PubMed:23894131, ECO:0000269|PubMed:24417481, ECO:0000269|PubMed:29271514, ECO:0000269|PubMed:30718304}.

Activity regulation: Under non-stress conditions, Spx is degraded by ClpXP and, to a lesser extent, by ClpCP (PubMed:12057962, PubMed:12642660, PubMed:19074380). Efficient dedradation by ClpXP requires the adapter protein SpxH/YjbH (PubMed:17908206, PubMed:19074380). Binding to SpxH/YjbH reduces the overall conformational flexibility of Spx and stabilizes the C-terminal ClpX recognition region of Spx (PubMed:30982633). In addition, activity is modulated by the formation of a disulfide bound within the N-terminal Cys-X-X-Cys (CXXC) motif, which is required for the transcriptional activation of trxA and trxB, or for the activation of msrAB operon expression following paraquat oxidative stress (PubMed:15659166, PubMed:18662407). However, it seems that formation of the disulfide bound is not essential for induction of all Spx-controlled genes, as for example the case of BSH biosynthesis genes (PubMed:23894131). Similarly, induction of the Spx regulon during cell wall stress is not accompanied by oxidation of the disulfide switch, but requires Spx stabilization by the anti-adapter protein SpxO/YirB (PubMed:29271514, PubMed:30001325). {ECO:0000269|PubMed:12057962, ECO:0000269|PubMed:12642660, ECO:0000269|PubMed:15659166, ECO:0000269|PubMed:17908206, ECO:0000269|PubMed:18662407, ECO:0000269|PubMed:19074380, ECO:0000269|PubMed:23894131, ECO:0000269|PubMed:29271514, ECO:0000269|PubMed:30001325, ECO:0000269|PubMed:30982633}.

Subunit: Interacts with the C-terminal domain of the alpha subunit of the RNAP (PubMed:12642660, PubMed:16249335, PubMed:19580872, PubMed:20084284, PubMed:22307755). A single Spx monomer interacts with RNAP to form the transcription activation complex (PubMed:22307755). Interacts with the adapter protein SpxH/YjbH (PubMed:19074380, PubMed:24942655, PubMed:30982633). {ECO:0000269|PubMed:12642660, ECO:0000269|PubMed:16249335, ECO:0000269|PubMed:19074380, ECO:0000269|PubMed:19580872, ECO:0000269|PubMed:20084284, ECO:0000269|PubMed:22307755, ECO:0000269|PubMed:24942655, ECO:0000269|PubMed:30982633}.

Subcellular location: Cytoplasm {ECO:0000305}.

Induction: Transcribed from at least five promoters located in the yjbC regulatory region or in the yjbC-spx intergenic region (PubMed:17158660, PubMed:29271514). Induced by heat, salt, ethanol and disulfide stress and also by phosphate limitation (PubMed:11544224, PubMed:14597697, PubMed:24417481). Induced by cell wall stress but not by membrane stress (PubMed:29271514). Transcribed under partial control of SigM ECF sigma factor (PubMed:17434969, PubMed:29271514). Repressed by YodB and PerR. YodB protects a region that includes the P3 -10 and -35 regions, while PerR binds to a region downstream of the P3 transcriptional start site (PubMed:17158660). {ECO:0000269|PubMed:11544224, ECO:0000269|PubMed:14597697, ECO:0000269|PubMed:17158660, ECO:0000269|PubMed:17434969, ECO:0000269|PubMed:24417481, ECO:0000269|PubMed:29271514}.

Domain: The C-terminal region is essential for structural folding and for interaction with SpxH/YjbH (PubMed:24942655). A conformational change during oxidation of Spx to the disulfide form likely alters the structure of Spx alpha helix alpha4, which contains residues that function in transcriptional activation and Spx/RNAP-promoter interaction (PubMed:20084284). {ECO:0000269|PubMed:20084284, ECO:0000269|PubMed:24942655}.

Disruption phenotype: Inactivation of the gene results in ClpP- independent competence development as well as partial suppression of the sporulation defect conferred by clpP mutation (PubMed:11703662). Null mutant shows hypersensitivity to disulfide stress and to paraquat (PubMed:14597697, PubMed:18662407). Mutants have increased sensitivity toward cell wall active antibiotics inhibiting both early and late steps in peptidoglycan synthesis (PubMed:29271514). Cells lacking the gene are defective in thermotolerance (PubMed:24417481). {ECO:0000269|PubMed:11703662, ECO:0000269|PubMed:14597697, ECO:0000269|PubMed:18662407, ECO:0000269|PubMed:24417481, ECO:0000269|PubMed:29271514}.

Similarity: Belongs to the ArsC family. Spx subfamily. {ECO:0000255|HAMAP-Rule:MF_01132, ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Bacillus subtilis (strain 168).
Taxonomy:		Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.



Function:		Global transcriptional regulator that plays a key role in stress response and exerts either positive or negative regulation of genes (PubMed:12642660, PubMed:15659166, PubMed:16885442, PubMed:18662407, PubMed:18687074, PubMed:29271514). Acts by interacting with the C-terminal domain of the alpha subunit of the RNA polymerase (RNAP) (PubMed:12642660, PubMed:15659166, PubMed:18687074, PubMed:20084284). This interaction can enhance binding of RNAP to the promoter region of target genes and stimulate their transcription, or block interaction of RNAP with activator proteins and repress transcription (PubMed:12642660, PubMed:15659166, PubMed:18687074, PubMed:20084284). Exhibits no DNA-binding activity (PubMed:15659166, PubMed:18687074). {ECO:0000269\|PubMed:12642660, ECO:0000269\|PubMed:15659166, ECO:0000269\|PubMed:16885442, ECO:0000269\|PubMed:18662407, ECO:0000269\|PubMed:18687074, ECO:0000269\|PubMed:20084284, ECO:0000269\|PubMed:29271514}.



Function:		Induces the expression of a large number of genes in response to a variety of stress conditions, such as disulfide, heat and cell wall stress, while concurrently repressing transcription of genes involved in various developmental and growth-related pathways during periods of extreme stress (PubMed:12642660, PubMed:14597697). Functions in the oxidative stress response via induction of the transcription of thioredoxin (trxA) and thioredoxin reductase (trxB) during thiol- specific oxidative (disulfide) stress (PubMed:14597697, PubMed:15659166, PubMed:18687074). Mediates response to oxidative stress caused by paraquat (PQ) via induction of the methionine sulfoxide reductase genes, msrA and msrB (PubMed:18662407). Also acts as a transcriptional activator of the bacillithiol (BSH) biosynthesis genes in response to oxidizing conditions and thio-reactive compounds (PubMed:23894131). Involved in heat stress response and thermotolerance development, which results in diminished cellular protein aggregates (PubMed:24417481). Plays an important adaptive role in the cell wall stress response (PubMed:29271514). Participates in sulfate-dependent control of organosulfur metabolism. Negatively controls, via CymR, the expression of the organosulfur utilization operons ytmI, yxeI and ssu, and directly activates yrrT operon expression during growth in medium containing methionine as sole sulfur source (PubMed:16885442). Negatively affects competence and sporulation (PubMed:11703662, PubMed:12028382). Inhibits biofilm formation in response to disulfide stress by repressing biofilm matrix genes (PubMed:30718304). {ECO:0000269\|PubMed:11703662, ECO:0000269\|PubMed:12028382, ECO:0000269\|PubMed:12642660, ECO:0000269\|PubMed:14597697, ECO:0000269\|PubMed:15659166, ECO:0000269\|PubMed:16885442, ECO:0000269\|PubMed:18662407, ECO:0000269\|PubMed:18687074, ECO:0000269\|PubMed:23894131, ECO:0000269\|PubMed:24417481, ECO:0000269\|PubMed:29271514, ECO:0000269\|PubMed:30718304}.


Activity regulation:		Under non-stress conditions, Spx is degraded by ClpXP and, to a lesser extent, by ClpCP (PubMed:12057962, PubMed:12642660, PubMed:19074380). Efficient dedradation by ClpXP requires the adapter protein SpxH/YjbH (PubMed:17908206, PubMed:19074380). Binding to SpxH/YjbH reduces the overall conformational flexibility of Spx and stabilizes the C-terminal ClpX recognition region of Spx (PubMed:30982633). In addition, activity is modulated by the formation of a disulfide bound within the N-terminal Cys-X-X-Cys (CXXC) motif, which is required for the transcriptional activation of trxA and trxB, or for the activation of msrAB operon expression following paraquat oxidative stress (PubMed:15659166, PubMed:18662407). However, it seems that formation of the disulfide bound is not essential for induction of all Spx-controlled genes, as for example the case of BSH biosynthesis genes (PubMed:23894131). Similarly, induction of the Spx regulon during cell wall stress is not accompanied by oxidation of the disulfide switch, but requires Spx stabilization by the anti-adapter protein SpxO/YirB (PubMed:29271514, PubMed:30001325). {ECO:0000269\|PubMed:12057962, ECO:0000269\|PubMed:12642660, ECO:0000269\|PubMed:15659166, ECO:0000269\|PubMed:17908206, ECO:0000269\|PubMed:18662407, ECO:0000269\|PubMed:19074380, ECO:0000269\|PubMed:23894131, ECO:0000269\|PubMed:29271514, ECO:0000269\|PubMed:30001325, ECO:0000269\|PubMed:30982633}.
Subunit:		Interacts with the C-terminal domain of the alpha subunit of the RNAP (PubMed:12642660, PubMed:16249335, PubMed:19580872, PubMed:20084284, PubMed:22307755). A single Spx monomer interacts with RNAP to form the transcription activation complex (PubMed:22307755). Interacts with the adapter protein SpxH/YjbH (PubMed:19074380, PubMed:24942655, PubMed:30982633). {ECO:0000269\|PubMed:12642660, ECO:0000269\|PubMed:16249335, ECO:0000269\|PubMed:19074380, ECO:0000269\|PubMed:19580872, ECO:0000269\|PubMed:20084284, ECO:0000269\|PubMed:22307755, ECO:0000269\|PubMed:24942655, ECO:0000269\|PubMed:30982633}.
Subcellular location:		Cytoplasm {ECO:0000305}.
Induction:		Transcribed from at least five promoters located in the yjbC regulatory region or in the yjbC-spx intergenic region (PubMed:17158660, PubMed:29271514). Induced by heat, salt, ethanol and disulfide stress and also by phosphate limitation (PubMed:11544224, PubMed:14597697, PubMed:24417481). Induced by cell wall stress but not by membrane stress (PubMed:29271514). Transcribed under partial control of SigM ECF sigma factor (PubMed:17434969, PubMed:29271514). Repressed by YodB and PerR. YodB protects a region that includes the P3 -10 and -35 regions, while PerR binds to a region downstream of the P3 transcriptional start site (PubMed:17158660). {ECO:0000269\|PubMed:11544224, ECO:0000269\|PubMed:14597697, ECO:0000269\|PubMed:17158660, ECO:0000269\|PubMed:17434969, ECO:0000269\|PubMed:24417481, ECO:0000269\|PubMed:29271514}.
Domain:		The C-terminal region is essential for structural folding and for interaction with SpxH/YjbH (PubMed:24942655). A conformational change during oxidation of Spx to the disulfide form likely alters the structure of Spx alpha helix alpha4, which contains residues that function in transcriptional activation and Spx/RNAP-promoter interaction (PubMed:20084284). {ECO:0000269\|PubMed:20084284, ECO:0000269\|PubMed:24942655}.
Disruption phenotype:		Inactivation of the gene results in ClpP- independent competence development as well as partial suppression of the sporulation defect conferred by clpP mutation (PubMed:11703662). Null mutant shows hypersensitivity to disulfide stress and to paraquat (PubMed:14597697, PubMed:18662407). Mutants have increased sensitivity toward cell wall active antibiotics inhibiting both early and late steps in peptidoglycan synthesis (PubMed:29271514). Cells lacking the gene are defective in thermotolerance (PubMed:24417481). {ECO:0000269\|PubMed:11703662, ECO:0000269\|PubMed:14597697, ECO:0000269\|PubMed:18662407, ECO:0000269\|PubMed:24417481, ECO:0000269\|PubMed:29271514}.
Similarity:		Belongs to the ArsC family. Spx subfamily. {ECO:0000255\|HAMAP-Rule:MF_01132, ECO:0000305}.