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| − | * '''Description:''' Transcriptional regulator Spx, involved in regulation of many genes. <br/><br/> | + | * '''Description:''' negative regulator of competence, targets ComK to ClpCP degradation machine (in log Phase) <br/><br/> |
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| | {| align="right" border="1" cellpadding="2" | | {| align="right" border="1" cellpadding="2" |
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| | |style="background:#ABCDEF;" align="center"|'''Gene name''' | | |style="background:#ABCDEF;" align="center"|'''Gene name''' |
| − | |''spx'' | + | |''mecA'' |
| | |- | | |- |
| − | |style="background:#ABCDEF;" align="center"| '''Synonyms''' || ''yjbD '' | + | |style="background:#ABCDEF;" align="center"| '''Synonyms''' || '' '' |
| | |- | | |- |
| − | |style="background:#ABCDEF;" align="center"| '''Essential''' || no | + | |style="background:#ABCDEF;" align="center"| '''Essential''' || no |
| | |- | | |- |
| − | |style="background:#ABCDEF;" align="center"| '''Product''' || transcriptional regulator Spx | + | |style="background:#ABCDEF;" align="center"| '''Product''' || adaptor protein |
| | |- | | |- |
| − | |style="background:#ABCDEF;" align="center"|'''Function''' || negative and positive regulator of many genes | + | |style="background:#ABCDEF;" align="center"|'''Function''' || control of ComK degradation, regulation of competence |
| | |- | | |- |
| − | |style="background:#ABCDEF;" align="center"| '''MW, pI''' || 15,5 kDa, 7.80 | + | |style="background:#ABCDEF;" align="center"| '''MW, pI''' || 25 kDa, 4.209 |
| | |- | | |- |
| − | |style="background:#ABCDEF;" align="center"| '''Gene length, protein length''' || 393 bp, 131 amino acids | + | |style="background:#ABCDEF;" align="center"| '''Gene length, protein length''' || 654 bp, 218 aa |
| | |- | | |- |
| − | |style="background:#ABCDEF;" align="center"|'''Immediate neighbours''' || ''[[yjbC]]'', ''[[yjbE]]'' | + | |style="background:#ABCDEF;" align="center"|'''Immediate neighbours''' || ''[[yjbE]]'', ''[[yjbF]]'' |
| | |- | | |- |
| − | |colspan="2" style="background:#FAF8CC;" align="center"|'''Get the DNA and protein [http://srs.ebi.ac.uk/srsbin/cgi-bin/wgetz?-e+[EMBLCDS:CAB13007]+-newId sequences] <br/> (Barbe ''et al.'', 2009)''' | + | |colspan="2" style="background:#FAF8CC;" align="center"|'''Get the DNA and protein [http://srs.ebi.ac.uk/srsbin/cgi-bin/wgetz?-e+[EMBLCDS:CAB13009]+-newId sequences] <br/> (Barbe ''et al.'', 2009)''' |
| | |- | | |- |
| − | |colspan="2" | '''Genetic context''' <br/> [[Image:spx_context.gif]] | + | |colspan="2" | '''Genetic context''' <br/> [[Image:mecA_context.gif]] |
| | <div align="right"> <small>This image was kindly provided by [http://genolist.pasteur.fr/SubtiList/ SubtiList]</small></div> | | <div align="right"> <small>This image was kindly provided by [http://genolist.pasteur.fr/SubtiList/ SubtiList]</small></div> |
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| | <br/><br/> | | <br/><br/> |
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| | =The gene= | | =The gene= |
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| | === Basic information === | | === Basic information === |
| | | | |
| − | * '''Coordinates:''' 1227010 - 1227402 | + | * '''Coordinates:''' |
| | | | |
| | ===Phenotypes of a mutant === | | ===Phenotypes of a mutant === |
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| − | Loss of up-regulation of the methionine sulfoxide reductase (''[[mrsA]]-[[mrsB]]'') operon in response to thiol specific oxidative stress, also loss of ''[[trxA]]'' and ''[[trxB]]'' upregulation in response to thiol specific oxidative stress.
| |
| | | | |
| | === Database entries === | | === Database entries === |
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| − | * '''DBTBS entry:''' [http://dbtbs.hgc.jp/COG/prom/yjbCD.html] | + | * '''DBTBS entry:''' [http://dbtbs.hgc.jp/COG/prom/mecA.html] |
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| − | * '''SubtiList entry:''' [http://genolist.pasteur.fr/SubtiList/genome.cgi?gene_detail+BG13133 link] | + | * '''SubtiList entry:''' [http://genolist.pasteur.fr/SubtiList/genome.cgi?gene_detail+BG10680] |
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| | === Additional information=== | | === Additional information=== |
| | + | |
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| | =The protein= | | =The protein= |
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| | === Basic information/ Evolution === | | === Basic information/ Evolution === |
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| − | * '''Catalyzed reaction/ biological activity:''' Transcriptional regulator of many genes in response to thiol specific oxidative stress (transcription activator of'' [[trxA]]'' and ''[[trxB]]''). In addition, Spx inhibits transcription by binding to the C-terminal domain of the alpha subunit of RNAP ([[RpoA]]), disrupting complex formation between RNAP and certain transcriptional activator proteins like [[ResD]] and [[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. | + | * '''Catalyzed reaction/ biological activity:''' |
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| − | * '''Protein family:''' Arsenate Reductase (ArsC) family, Spx subfamily | + | * '''Protein family:''' |
| | | | |
| − | * '''Paralogous protein(s):''' [[MgsR]] | + | * '''Paralogous protein(s):''' [[YpbH]] |
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| | === Extended information on the protein === | | === Extended information on the protein === |
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| | * '''Kinetic information:''' | | * '''Kinetic information:''' |
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| − | * '''Domains:''' CXXC (10-13): Acts as a disulfide switch for the redox-sensitive transcriptional regulation of genes that function in thiol homeostasis. | + | * '''Domains:''' |
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| − | * '''Modification:''' Cysteine oxidation of the CXXC motif | + | * '''Modification:''' |
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| | * '''Cofactor(s):''' | | * '''Cofactor(s):''' |
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| | * '''Effectors of protein activity:''' | | * '''Effectors of protein activity:''' |
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| − | * '''Interactions:''' [[Spx]]-[[YjbH]], [[YjbH]]-[[Spx]] [http://www.ncbi.nlm.nih.gov/sites/entrez/19074380 PubMed], [[Spx]]-[[RpoA]] (C-terminal domain [http://www.ncbi.nlm.nih.gov/sites/entrez/12642660 PubMed] | + | * '''Interactions:''' [[ClpC]]-[[MecA]], |
| | + | |
| | * '''Localization:''' | | * '''Localization:''' |
| | | | |
| | === Database entries === | | === Database entries === |
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| − | * '''Structure:''' complex with C-terminal domain of [[RpoA]] [http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?Dopt=s&uid=35536 NCBI] | + | * '''Structure:''' |
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| | * '''Swiss prot entry:''' | | * '''Swiss prot entry:''' |
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| − | * '''KEGG entry:''' [http://www.genome.jp/dbget-bin/www_bget?bsu+BSU11500] | + | * '''KEGG entry:''' [http://www.genome.jp/dbget-bin/www_bget?bsu+BSU11520] |
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| | * '''E.C. number:''' | | * '''E.C. number:''' |
| | | | |
| | === Additional information=== | | === Additional information=== |
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| |
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| | =Expression and regulation= | | =Expression and regulation= |
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| − | * '''Operon:''' ''[[yjbC]]-[[spx]]'', ''[[spx]]'' | + | * '''Operon:''' ''[[mecA]]'' |
| − | | |
| − | * '''[[Sigma factor]]:''' four promoters upstream of ''[[yjbC]]'': [[SigW]], [[SigB]], [[SigX]], and unknown sigma [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=+10913081 PubMed],
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| − | :::: promoters upstream of ''spx'': [[SigA]], [[SigW]] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=+10913081 PubMed], [[SigM]] [http://www.ncbi.nlm.nih.gov/sites/entrez/17434969 PubMed]
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| − | * '''Regulation:''' induced by stress ([[SigB]]) [http://www.ncbi.nlm.nih.gov/pubmed/15805528 PubMed], Transcription is represed by [[PerR]] and [[YodB ]] [http://www.ncbi.nlm.nih.gov/sites/entrez/17158660 PubMed] | + | * '''[[Sigma factor]]:''' [[SigA]] |
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| − | * '''Regulatory mechanism:''' transcription repression | + | * '''Regulation:''' |
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| − | * '''Additional information:'''Post-translational control by [[ClpX]]-[[ClpP]]: Spx naturally contains a C-terminal sequence that resembles the [[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] | + | * '''Regulatory mechanism:''' |
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| − | Proteolysis is enhanced by [[YjbH]]. [http://www.ncbi.nlm.nih.gov/pubmed/19074380?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum PubMed]
| + | * '''Additional information:''' |
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| | =Biological materials = | | =Biological materials = |
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| − | * '''Mutant:''' ORB6781 (spc), ORB6876 (tet), available in [[Zuber]] lab | + | * '''Mutant:''' |
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| | * '''Expression vector:''' | | * '''Expression vector:''' |
| − |
| + | |
| | * '''lacZ fusion:''' | | * '''lacZ fusion:''' |
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| | * '''GFP fusion:''' | | * '''GFP fusion:''' |
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| − | * '''two-hybrid system:''' ''B. pertussis'' adenylate cyclase-based bacterial two hybrid system ([[BACTH]]), available in [[Stülke]] lab | + | * '''two-hybrid system:''' |
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| | * '''Antibody:''' | | * '''Antibody:''' |
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| | =Labs working on this gene/protein= | | =Labs working on this gene/protein= |
| − |
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| − | [[Peter Zuber]], Oregon Health and Science University, USA
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| − | [http://www.ogi.edu/people/dsp_person.cfm?person_id=411D6801-2A56-D16D-58A06B4480EDB9C7 Homepage]
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| − |
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| − | [[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]
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| | =Your additional remarks= | | =Your additional remarks= |
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| | =References= | | =References= |
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| − | # Höper et al. (2005) Comprehensive Characterization of the Contribution of Individual [[SigB]]-Dependent General Stress Genes to Stress Resistance of ''Bacillus subtilis''. J. Bact. '''187:''' 2810-2826 [http://www.ncbi.nlm.nih.gov/pubmed/15805528 PubMed] | + | # Author1, Author2 & Author3 (year) Title ''Journal'' '''volume:''' page-page. [http://www.ncbi.nlm.nih.gov/sites/entrez/PMID PubMed] |
| − | # Choi, S. Y., D. Reyes, M. Leelakriangsak, and P. Zuber. 2006. The global regulator Spx functions in the control of organosulfur metabolism in Bacillus subtilis. J. Bacteriol. 188:5741-5751. [http://www.ncbi.nlm.nih.gov/sites/entrez/16885442 PubMed]
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| − | # Eiamphungporn, W., and J. D. Helmann. 2008. The Bacillus subtilis sigma(M) regulon and its contribution to cell envelope stress responses. Mol. Microbiol. 67:830-848. [http://www.ncbi.nlm.nih.gov/sites/entrez/18179421 PubMed]
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| − | # Garg et al. 2009. The YjbH protein of Bacillus subtilis enhances ClpXP-catalyzed proteolysis of Spx. J. Bacteriol. 191: 1268-1277. [http://www.ncbi.nlm.nih.gov/sites/entrez/19074380 PubMed]
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| − | # Jervis et al. 2007. SigM-responsive genes of ''Bacillus subtilis'' and their promoters. J. Bacteriol. 189: 4534-4538. [http://www.ncbi.nlm.nih.gov/sites/entrez/17434969 PubMed]
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| − | # Larsson, J. T., A. Rogstam, and C. von Wachenfeldt. 2007. YjbH is a novel negative effector of the disulphide stress regulator, Spx, in Bacillus subtilis. Mol. Microbiol. 66:669-684. [http://www.ncbi.nlm.nih.gov/sites/entrez/17908206 PubMed]
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| − | # Leelakriangsak, M., K. Kobayashi, and P. Zuber. 2007. Dual negative control of spx transcription initiation from the P3 promoter by repressors PerR and YodB in Bacillus subtilis. J. Bacteriol. 189:1736-1744. [http://www.ncbi.nlm.nih.gov/sites/entrez/17158660 PubMed]
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| − | # Nakano, M. M., F. Hajarizadeh, Y. Zhu, and P. Zuber. 2001. Loss-of-function mutations in yjbD result in ClpX- and ClpP-independent competence development of Bacillus subtilis. Mol. Microbiol. 42:383-394.[http://www.ncbi.nlm.nih.gov/sites/entrez/11703662 PubMed]
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| − | # Nakano, S., K. N. Erwin, M. Ralle, and P. Zuber. 2005. Redox-sensitive transcriptional control by a thiol/disulphide switch in the global regulator, Spx. Mol. Microbiol. 55:498-510. [http://www.ncbi.nlm.nih.gov/sites/entrez/15659166 PubMed]
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| − | # Nakano, S., E. Küster-Schöck, A. D. Grossman, and P. Zuber. 2003. Spx dependent global transcriptional control is induced by thiol-specific oxidative stress in Bacillus subtilis. Proc. Natl. Acad. Sci. USA 100:13603-13608. [http://www.ncbi.nlm.nih.gov/sites/entrez/14597697 PubMed]
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| − | # Nakano, S., M. M. Nakano, Y. Zhang, M. Leelakriangsak, and P. Zuber. 2003. A regulatory protein that interferes with activator-stimulated transcription in bacteria. Proc. Natl. Acad. Sci. USA 100:4233-4238. [http://www.ncbi.nlm.nih.gov/sites/entrez/12642660 PubMed]
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| − | # Nakano, S., G. Zheng, M. M. Nakano, and P. Zuber. 2002. Multiple pathways of Spx (YjbD) proteolysis in Bacillus subtilis. J. Bacteriol. 184:3664-3670. [http://www.ncbi.nlm.nih.gov/sites/entrez/12057962 PubMed]
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| − | # Newberry, K. J., S. Nakano, P. Zuber, and R. G. Brennan. 2005. Crystal structure of the Bacillus subtilis anti-alpha, global transcriptional regulator, Spx, in complex with the alpha C-terminal domain of RNA polymerase. Proc. Natl. Acad. Sci. USA 102:15839-15844. [http://www.ncbi.nlm.nih.gov/sites/entrez/16249335 PubMed]
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| − | # Petersohn, A., J. Bernhardt, U. Gerth, D. Hoper, T. Koburger, U. Volker, and M. Hecker. 1999. Identification of sigma(B)-dependent genes in Bacillus subtilis using a promoter consensus-directed search and oligonucleotide hybridization. J. Bacteriol. 181:5718-5724. [http://www.ncbi.nlm.nih.gov/sites/entrez/10482513 PubMed]
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| − | # Reyes, D. Y. and P. Zuber. 2008. Activation of transcription initiation by Spx: formation of a transcription complex and identification of a cis-acting element required for transcriptional activation. Mol. Microbiol. 69:765-779. [http://www.ncbi.nlm.nih.gov/sites/entrez/18687074 PubMed]
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| − | # Thackray, P. D., and A. Moir. 2003. SigM, an extracytoplasmic function [[sigma factor]] of Bacillus subtilis, is activated in response to cell wall antibiotics, ethanol, heat, acid, and superoxide stress. J. Bacteriol. 185:3491-3498. [http://www.ncbi.nlm.nih.gov/sites/entrez/12775685 PubMed]
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| − | # Zhang, Y., S. Nakano, S. Y. Choi, and P. Zuber. 2006. Mutational analysis of the Bacillus subtilis RNA polymerase alpha C-terminal domain supports the interference model of Spx-dependent repression. J. Bacteriol. 188:4300-4311. [http://www.ncbi.nlm.nih.gov/sites/entrez/16740936 PubMed]
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| − | # Zhang, Y., and P. Zuber. 2007. Requirement of the zinc-binding domain of ClpX for Spx proteolysis in Bacillus subtilis and effects of disulfide stress on ClpXP activity. J. Bacteriol. 189:7669-7680. [http://www.ncbi.nlm.nih.gov/sites/entrez/17827297 PubMed]
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| − | # Zuber, P. 2004. Spx-RNA polymerase interaction and global transcriptional control during oxidative stress. J. Bacteriol. 186:1911-1918. [http://www.ncbi.nlm.nih.gov/sites/entrez/15028674 PubMed]
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