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spx [Thu Oct 01 2015 13:51:44 GMT+0200 (CEST)]
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spx [Thu Oct 01 2015 13:51:44 GMT+0200 (CEST)]

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
locus
BSU11500
pI
7.00
mw
15.00 kDa
function
negative and positive regulator of many genes
product
transcriptional regulator Spx
essential
no
synonyms
yjbD
Outlinks
KEGGBsubCycSubtiListUniProtExpression Browser

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]

    • [SW|Categories] containing this gene/protein

  • [SW|transcription factors and their control], [SW|general stress proteins (controlled by SigB)], [SW|cell envelope stress proteins (controlled by SigM, V, W, X, Y)], [SW|resistance against oxidative and electrophile stress]

    • This gene is a member of the following [SW|regulons]

  • [SW|PerR regulon], [SW|SigB regulon], [SW|SigM regulon], [SW|SigW regulon], [SW|SigX regulon]

    • Gene

    Coordinates on the chromosome (coding sequence)
    1,227,697 -> 1,228,092

    Phenotypes of a mutant

  • Loss of up-regulation of the methionine sulfoxide reductase (''[protein|search|msrA]-[protein|search|msrB]'') operon in response to thiol specific oxidative stress, also loss of ''[protein|search|trxA]'' and ''[protein|search|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'' [protein|search|trxA]'' and ''[protein|search|trxB]'')
  • in addition, Spx inhibits transcription by binding to the C-terminal domain of the alpha subunit of RNAP ([protein|search|RpoA]), disrupting complex formation between RNAP and certain transcriptional activator proteins like [protein|search|ResD] and [protein|search|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 initiation
  • involved in competence regulation [Pubmed|11703662]

    • Protein family

  • Spx subfamily (according to Swiss-Prot) Arsenate Reductase (ArsC) family, Spx subfamily

    • Paralogous protein(s)

  • [protein|search|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 the CXXC motif

    • Structure

  • [PDB|1Z3E] complex with C-terminal domain of [protein|search|RpoA] [http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?Dopt=s&uid=35536 NCBI]

    • [SW|Localization]

  • cytoplasm (according to Swiss-Prot)

    • [SW|Interactions]

  • [protein|search|Spx]-[protein|search|YjbH] [Pubmed|19074380]
  • [protein|search|Spx]-[protein|search|RpoA] (C-terminal domain) [Pubmed|12642660,22307755]
  • [protein|search|Spx]-[protein|search|ClpP]/[protein|search|ClpX] (degradation of [protein|search|Spx]) [Pubmed|17827297]

    • Expression and Regulation

    Operon

  • ''[protein|search|yjbC]-[protein|search|spx]'' [Pubmed|10913081]
  • ''[protein|search|spx]'' [Pubmed|10913081]

    • [SW|Sigma factor]

  • four promoters upstream of ''[protein|search|yjbC]'': [protein|search|SigW], [protein|search|SigB], [protein|search|SigX] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10913081 PubMed], [protein|search|SigM] [Pubmed|17434969]
  • promoters upstream of ''spx'': [protein|search|SigA], [protein|search|SigW] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10913081 PubMed], [protein|search|SigM] [Pubmed|17434969]

    • Regulation

  • induced by stress ([protein|search|SigB]) [Pubmed|15805528]
  • transcription is represed by [protein|search|PerR] and [SW|YodB ] [Pubmed|17158660]
  • repressed in the absence of hydrogen peroxide ([protein|search|PerR]) [Pubmed|17158660]
  • upregulated in response to enduracidin [Pubmed|20057163]

    • Regulatory mechanism

  • transcription repression
  • [protein|search|PerR]: transcription repression [Pubmed|17158660]

    • Additional information

  • post-translational control by [protein|search|ClpX]-[protein|search|ClpP]: Spx naturally contains a C-terminal sequence that resembles the [protein|search|SsrA] tag and targets the protein for degradation. [http://www.ncbi.nlm.nih.gov/pubmed/12642660?ordinalpos=27&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum PubMed]
  • proteolysis is enhanced by [protein|search|YjbH] [http://www.ncbi.nlm.nih.gov/pubmed/19074380?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum PubMed] and counter-acted by [protein|search|YirB] [PubMed|21378193]
  • [protein|search|YjbH] aggregates under stress conditions, resulting in the inability to bind to [protein|search|Spx], and therefore in stabilization of [protein|search|Spx], in contrast active soluble [protein|search|YjbH] under non-stressed conditions targets [protein|search|Spx] to degradation [PubMed|25353645]
  • the mRNA is substantially stabilized upon depletion of [Rny|search|RNase Y] (the half-life of the monocistronic 'spx' mRNA increases from 1 to 6 min) [PubMed|21815947]

    • Biological materials

    Mutant

  • GPUG3 (spc), available in [SW|Ulf Gerth]s and [SW|Jörg Stülke]s labs
  • ORB6781 (spc), ORB6876 (tet), available in [SW|Zuber] lab, also available in the [SW|Stülke] lab
  • 1A917 ( ''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]

    • two-hybrid system

  • ''B. pertussis'' adenylate cyclase-based bacterial two hybrid system ([SW|BACTH]), available in [SW|Stülke] lab

    • Labs working on this gene/protein

  • [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

    • The [SW|Spx regulon]

  • 15937167,14597697,15028674,22904090

    • 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