transcriptional regulator Spx, involved in regulation of many genes, important for the prevention of protein aggregation during severe heat stress, required for protection against paraquat stress
function
negative and positive regulator of many genes
product
transcriptional regulator Spx
Genomic Context
categories
[category|SW 3|Information processing] → [category|SW 3.4|Regulation of gene expression] → [category|SW 3.4.2|Transcription factors and their control] → [category|SW 3.4.2.5|Transcription factors/ other][category|SW 4|Lifestyles] → [category|SW 4.3|Coping with stress] → [category|SW 4.3.1|General stress proteins (controlled by SigB)][category|SW 4|Lifestyles] → [category|SW 4.3|Coping with stress] → [category|SW 4.3.2|Cell envelope stress proteins (controlled by SigM, V, W, X, Y)][category|SW 4|Lifestyles] → [category|SW 4.3|Coping with stress] → [category|SW 4.3.8|Resistance against oxidative and electrophile stress][category|SW 6|Groups of genes] → [category|SW 6.4|Phosphoproteins] → [category|SW 6.4.1|Phosphorylation on an Arg residue]Gene
Coordinates
1,227,697 1,228,092
Phenotypes of a mutant
Loss of up-regulation of the methionine sulfoxide reductase (''[gene|389245FDE13226D65DF117E28B5DA346DC856860|msrA]-[gene|BF8A3C916C4B673D30AEF7C330C9BD5A487AB0EA|msrB]'') operon in response to thiol specific oxidative stress, also loss of ''[gene|4E5C84FDC8FE2FEFF47306C91ECAB7F17D3E38E9|trxA]'' and ''[gene|1BC439BBCD5FE19D5780519D7E4317C2EFF0D21B|trxB]'' upregulation in response to thiol specific oxidative stress.The protein
Catalyzed reaction/ biological activity
transcriptional regulator of many genes in response to thiol specific oxidative stress (transcription activator of [gene|4E5C84FDC8FE2FEFF47306C91ECAB7F17D3E38E9|trxA] and [gene|1BC439BBCD5FE19D5780519D7E4317C2EFF0D21B|trxB])in addition, Spx inhibits transcription by binding to the C-terminal domain of the alpha subunit of RNAP ([protein|5996A5C25E108A3C4562686BF34A59CB14FD56EB|RpoA]), disrupting complex formation between RNAP and certain transcriptional activator proteins like [protein|1E829D639BADDC6BDC9B5FB4C97A632A53FDDB24|ResD] and [protein|7832489F11F606BCF637EC23BAAB41AD10237EBB|ComA]in response to thiol specific oxidative stress, Spx can also activate transcription, making it a general regulator that exerts both positive and negative control over transcription initiationinvolved in competence regulation [Pubmed|11703662]inhibits expression of translation-related genes during heat stress [pubmed|30480837]Protein family
ArsC family (with [protein|6A38DAA96F7BBF31FD8A4018A8CA7A72F3C28F79|MgsR] and [protein|5278DD377B110CC14E239B9428F1985B472EEDF5|YusI], according to UniProt)Paralogous protein(s)
[protein|6A38DAA96F7BBF31FD8A4018A8CA7A72F3C28F79|MgsR] [SW|Domains]
CXXC (10-13): Acts as a disulfide switch for the redox-sensitive transcriptional regulation of genes that function in thiol homeostasis.Modification
Cysteine oxidation of CXXC motifphosphorylation on R14, R91, R100, R112 by McsB, dephosphosphorylation by YwlE [pubmed|30962353]Structure
[PDB|1Z3E] complex with C-terminal domain of [protein|5996A5C25E108A3C4562686BF34A59CB14FD56EB|RpoA] [pubmed|16249335][PDB|6GHB] (complexed with oxidized Geobacillus kaustophilus [protein|87124945A1CBF7990856FBEB9EAD25096DAC0868|YjbH]) [Pubmed|30982633][PDB|6GHO] (complexed with Geobacillus kaustophilus [protein|87124945A1CBF7990856FBEB9EAD25096DAC0868|YjbH]) [Pubmed|30982633][SW|Localization]
cytoplasm (according to UniProt)Expression and Regulation
Operons
genes
[gene|2C6386E9A63F410558D168798D077DF91590F454|spx]
description
[Pubmed|10913081]
sigma factors
[protein|3D974DD2967C7F8FD4E3C2AF42617B8AE9F0296D|SigW]: sigma factor, four promoters upstream of [protein|54D021424B31A8244F0F4B32EF9483CF27F90D43|YjbC], in [regulon|3D974DD2967C7F8FD4E3C2AF42617B8AE9F0296D|SigW regulon][protein|580011DE5DC40EC9E7E0512791D328FAA010DCB8|SigB]: sigma factor, four promoters upstream of [protein|54D021424B31A8244F0F4B32EF9483CF27F90D43|YjbC], in [regulon|580011DE5DC40EC9E7E0512791D328FAA010DCB8|SigB regulon][protein|E77364F274A520FCCA9F5C9504E317B047BA29E6|SigX]: sigma factor, four promoters upstream of [protein|54D021424B31A8244F0F4B32EF9483CF27F90D43|YjbC] [PubMed|10913081], in [regulon|E77364F274A520FCCA9F5C9504E317B047BA29E6|SigX regulon][protein|081DF3EE9FA56209D648C7677188C61CE3AA8E41|SigM]: sigma factor, four promoters upstream of [protein|54D021424B31A8244F0F4B32EF9483CF27F90D43|YjbC] [Pubmed|17434969], in [regulon|081DF3EE9FA56209D648C7677188C61CE3AA8E41|SigM regulon][protein|360F48D576DE950DF79C1A2677B7A35A8D8CC30C|SigA]: sigma factor, four promoters upstream of [protein|54D021424B31A8244F0F4B32EF9483CF27F90D43|YjbC], in [regulon|360F48D576DE950DF79C1A2677B7A35A8D8CC30C|SigA regulon]regulatory mechanism
[protein|00BCAAE16576DC5426A652580C69A570FC7A1C2C|PerR]: repression, [Pubmed|17158660], in [regulon|00BCAAE16576DC5426A652580C69A570FC7A1C2C|PerR regulon]regulation
induced by stress ([protein|580011DE5DC40EC9E7E0512791D328FAA010DCB8|SigB]) [Pubmed|15805528]view in new tabgenes
[gene|54D021424B31A8244F0F4B32EF9483CF27F90D43|yjbC]-[gene|2C6386E9A63F410558D168798D077DF91590F454|spx]
description
[Pubmed|10913081]
sigma factors
[protein|081DF3EE9FA56209D648C7677188C61CE3AA8E41|SigM]: sigma factor, [Pubmed|17434969], in [regulon|081DF3EE9FA56209D648C7677188C61CE3AA8E41|SigM regulon][protein|3D974DD2967C7F8FD4E3C2AF42617B8AE9F0296D|SigW]: sigma factor, in [regulon|3D974DD2967C7F8FD4E3C2AF42617B8AE9F0296D|SigW regulon][protein|580011DE5DC40EC9E7E0512791D328FAA010DCB8|SigB]: sigma factor, in [regulon|580011DE5DC40EC9E7E0512791D328FAA010DCB8|SigB regulon][protein|E77364F274A520FCCA9F5C9504E317B047BA29E6|SigX]: sigma factor, [PubMed|10913081], in [regulon|E77364F274A520FCCA9F5C9504E317B047BA29E6|SigX regulon]regulatory mechanism
[protein|00BCAAE16576DC5426A652580C69A570FC7A1C2C|PerR]: repression, [Pubmed|17158660], in [regulon|00BCAAE16576DC5426A652580C69A570FC7A1C2C|PerR regulon]regulation
induced by stress ([protein|580011DE5DC40EC9E7E0512791D328FAA010DCB8|SigB]) [Pubmed|15805528]view in new tabadditional information
post-translational control by [protein|297F53DAD3351E0C55108DD2C93B78FFB174438C|ClpX]-[protein|CB06A70DE7462CEB7AF5D8C28943C878DD56DE1A|ClpP]: Spx naturally contains a C-terminal sequence that resembles the [protein|5C12BB19B975F7FEBCFA119DAC66338C20FCECFA|SsrA] tag and targets the protein for degradation. [pubmed|12642660]Biological materials
Mutant
MGNA-B151 (yjbD::erm), available at the [https://shigen.nig.ac.jp/bsub/resource/strainGeneDisrupted/detail/1150 NBRP B. subtilis, Japan]GPUG3 (spc), available in [SW|Ulf Gerth]s and [SW|Jörg Stülke]'s labsGP1788 (spc), available in [SW|Jörg Stülke]'s labORB6781 (spc), ORB6876 (tet), available in [SW|Zuber] lab, also available in [SW|Jörg Stülke]'s lab1A917 ( ''spx''::''spec''), [Pubmed|21949854], available at [http://pasture.asc.ohio-state.edu/BGSC/getdetail.cfm?bgscid=1A917&Search=1A917 BGSC]1A916 ( ''spx''::''tet''), [Pubmed|21949854], available at [http://pasture.asc.ohio-state.edu/BGSC/getdetail.cfm?bgscid=1A916&Search=1A916 BGSC]BKE11500 ([gene|2C6386E9A63F410558D168798D077DF91590F454|spx]::erm trpC2) available at [http://www.bgsc.org/getdetail.php?bgscid=BKE11500 BGSC], [Pubmed|28189581], upstream reverse: _UP1_CATTCATCTTCACTCCTCTA, downstream forward: _UP4_TAATAGATCGTATCATCAAABKK11500 ([gene|2C6386E9A63F410558D168798D077DF91590F454|spx]::kan trpC2) available at [http://www.bgsc.org/getdetail.php?bgscid=BKK11500 BGSC], [Pubmed|28189581], upstream reverse: _UP1_CATTCATCTTCACTCCTCTA, downstream forward: _UP4_TAATAGATCGTATCATCAAAtwo-hybrid system
''B. pertussis'' adenylate cyclase-based bacterial two hybrid system ([SW|BACTH]), available in [SW|Jörg Stülke]'s lablabs
[SW|Peter Zuber], Oregon Health and Science University, USA, [http://www.ogi.edu/people/dsp_person.cfm?person_id=411D6801-2A56-D16D-58A06B4480EDB9C7 Homepage][SW|Richard Brennan], Houston, Texas, USA [http://www.mdanderson.org/departments/biochem/display.cfm?id=556ef368-6c81-4043-b74f350d41dd06cb&method=displayfull&pn=a8427ebd-d0ff-11d4-80fd00508b603a14 Homepage]References
Reviews
19575568,20626317,30830258,31655740 The [SW|Spx regulon]
15937167,14597697,15028674,22904090,29271514 Structural analysis of Spx
19580872,16249335,23813734 Original Publications
21378193,22307755,18487332,17908206,17434969,17158660,19074380,15805528,18662407,16885442,18179421,17434969,17908206,17158660,11703662,15659166,12642660,12057962,10482513,18687074,12775685,16740936,17827297,20084284,20057163,10913081,21815947,23894131,23934352,22582280,24417481,24942655,25353645,25433860,27191337,28484046,30001325,30480837,30718304,30982633,30962353