Sda

• Description: developmental checkpoint protein, inhibits the autokinase activity of KinA and KinB, control of the phosphorelay

Gene name	sda
Synonyms
Essential	no
Product	developmental checkpoint protein
Function	mediates a developmental checkpoint coupling initiation of sporulation (phosphorylation of Spo0A) to the function of replication initiation proteins
Gene expression levels in SubtiExpress: sda
Interactions involving this protein in SubtInteract: Sda
Function and regulation of this protein in SubtiPathways: sda
MW, pI	6 kDa, 5.605
Gene length, protein length	156 bp, 52 aa
Immediate neighbours	yloV, yqeF
Sequences	Protein DNA DNA_with_flanks
Genetic context This image was kindly provided by SubtiList
Expression at a glance   PubMed

Categories containing this gene/protein

phosphorelay

This gene is a member of the following regulons

DnaA regulon, LexA regulon

The gene

Basic information

• Locus tag: BSU25690

Phenotypes of a mutant

• sporulates at a higher frequency
• will sporulate in the presence of replication stress

Database entries

• BsubCyc: BSU25690

• DBTBS entry: [1]

• SubtiList entry: [2]

The protein

Basic information/ Evolution

• Catalyzed reaction/ biological activity: Sda is a checkpoint protein that is upregulated in response to replication stress PubMed. Sda inhibits the autokinase activity of KinA (and likely KinB as well). This in its turn results in reduced levels of Spo0A~P. Thus, replication stressed cells will not initiate sporulation.

• Protein family:

• Paralogous protein(s):

Extended information on the protein

• Kinetic information:

• Domains:

• Modification:

• Cofactor(s):

• Effectors of protein activity:

• Interactions:
  • KinB-Sda PubMed
  • KinA-Sda PubMed

• Localization:

Database entries

• BsubCyc: BSU25690

• Structure: 3D36 (from Geobacillus stearothermophilus, complex with KinB) PubMed, 1PV0

• UniProt: Q7WY62

• KEGG entry: [3]

• E.C. number:

Additional information

• Sda is rapidly degraded by the ClpP/X system because of some uncharged residues at its C-terminus PubMed

Expression and regulation

• Operon: sda PubMed

• Expression browser: sda PubMed

• Sigma factor: SigA PubMed

• Regulation:
  • induced by DNA damage (LexA) PubMed

• Regulatory mechanism:
  • DnaA: transcription activation under replication stress PubMed
  • LexA: transcription repression PubMed

• Additional information:
  • Sda is rapidly turned over by the ClpP/X system because of some uncharged residues at its C-terminus PubMed.
  • An antisense RNA is predicted for sda PubMed

Biological materials

• Mutant:
  • 1A1034 (no resistance), PubMed, available at BGSC

• Expression vector:

• lacZ fusion:

• GFP fusion:

• two-hybrid system:

• Antibody:

Labs working on this gene/protein

Bill Burkholder Homepage

References

Original publications

Janet L Smith, Alan D Grossman
In Vitro Whole Genome DNA Binding Analysis of the Bacterial Replication Initiator and Transcription Factor DnaA.
PLoS Genet: 2015, 11(5);e1005258
[PubMed:26020636] [WorldCat.org] [DOI] (I e)

Irnov Irnov, Cynthia M Sharma, Jörg Vogel, Wade C Winkler
Identification of regulatory RNAs in Bacillus subtilis.
Nucleic Acids Res: 2010, 38(19);6637-51
[PubMed:20525796] [WorldCat.org] [DOI] (I p)

Jan-Willem Veening, Heath Murray, Jeff Errington
A mechanism for cell cycle regulation of sporulation initiation in Bacillus subtilis.
Genes Dev: 2009, 23(16);1959-70
[PubMed:19684115] [WorldCat.org] [DOI] (I p)

David A Jacques, Margaret Streamer, Susan L Rowland, Glenn F King, J Mitchell Guss, Jill Trewhella, David B Langley
Structure of the sporulation histidine kinase inhibitor Sda from Bacillus subtilis and insights into its solution state.
Acta Crystallogr D Biol Crystallogr: 2009, 65(Pt 6);574-81
[PubMed:19465772] [WorldCat.org] [DOI] (I p)

Matthew J Bick, Valerie Lamour, Kanagalaghatta R Rajashankar, Yuliya Gordiyenko, Carol V Robinson, Seth A Darst
How to switch off a histidine kinase: crystal structure of Geobacillus stearothermophilus KinB with the inhibitor Sda.
J Mol Biol: 2009, 386(1);163-77
[PubMed:19101565] [WorldCat.org] [DOI] (I p)

Shu Ishikawa, Yoshitoshi Ogura, Mika Yoshimura, Hajime Okumura, Eunha Cho, Yoshikazu Kawai, Ken Kurokawa, Taku Oshima, Naotake Ogasawara
Distribution of stable DnaA-binding sites on the Bacillus subtilis genome detected using a modified ChIP-chip method.
DNA Res: 2007, 14(4);155-68
[PubMed:17932079] [WorldCat.org] [DOI] (P p)

Andrew E Whitten, David A Jacques, Boualem Hammouda, Tracey Hanley, Glenn F King, J Mitchell Guss, Jill Trewhella, David B Langley
The structure of the KinA-Sda complex suggests an allosteric mechanism of histidine kinase inhibition.
J Mol Biol: 2007, 368(2);407-20
[PubMed:17350039] [WorldCat.org] [DOI] (P p)

Michael V Ruvolo, Kathleen E Mach, William F Burkholder
Proteolysis of the replication checkpoint protein Sda is necessary for the efficient initiation of sporulation after transient replication stress in Bacillus subtilis.
Mol Microbiol: 2006, 60(6);1490-508
[PubMed:16796683] [WorldCat.org] [DOI] (P p)

Nora Au, Elke Kuester-Schoeck, Veena Mandava, Laura E Bothwell, Susan P Canny, Karen Chachu, Sierra A Colavito, Shakierah N Fuller, Eli S Groban, Laura A Hensley, Theresa C O'Brien, Amish Shah, Jessica T Tierney, Louise L Tomm, Thomas M O'Gara, Alexi I Goranov, Alan D Grossman, Charles M Lovett
Genetic composition of the Bacillus subtilis SOS system.
J Bacteriol: 2005, 187(22);7655-66
[PubMed:16267290] [WorldCat.org] [DOI] (P p)

Susan L Rowland, William F Burkholder, Katherine A Cunningham, Mark W Maciejewski, Alan D Grossman, Glenn F King
Structure and mechanism of action of Sda, an inhibitor of the histidine kinases that regulate initiation of sporulation in Bacillus subtilis.
Mol Cell: 2004, 13(5);689-701
[PubMed:15023339] [WorldCat.org] [DOI] (P p)

W F Burkholder, I Kurtser, A D Grossman
Replication initiation proteins regulate a developmental checkpoint in Bacillus subtilis.
Cell: 2001, 104(2);269-79
[PubMed:11207367] [WorldCat.org] [DOI] (P p)