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BirA DNA-binding transcriptional repressor

Synonyms: BirA, BirA-bio-5'-AMP
Summary:
The biotin repressor, BirA, coordinately represses transcription of the divergent genes that are necessary for the synthesis of biotin |CITS:[6177001][366433]|. BirA is a bifunctional protein that possesses both regulatory and enzymatic activities: it acts as the DNA-binding transcriptional repressor of the biotin operon and also exhibits biotin ligase activity |CITS:[6129246]|.
The specific inducer for BirA is biotinyl-5'-adenylate (bio-5'-AMP). In the presence of bio-5'-AMP, BirA binds to 40-nucleotide-long DNA target sites in the bioA/bioBFCD intergenic region to coordinately repress transcription of bioAp and bioBp |CITS:[9485476][1659455]|. BirA-bio-5'-AMP has been observed to be predominantly monomeric in solution |CITS:[6129246][8373769][9485476]|, whereas more recent studies indicate that dimerization occurs before DNA binding |CITS:[12527300]|. Biotinyl-5'-adenylate |CITS:[10529178]| and biotin |CITS:[11353844][350835]| stimulate dimerization and DNA binding.
The effector bio-5'-AMP is also a substrate in the BirA-mediated biotinylation of the biotin carboxyl carrier protein monomer (apoBCCP), and this relationship results in repression of the biotin operon when the abundance of apoBCCP (and therefore the cellular demand for biotin) is reduced |CITS:[9750231]|. This repression is controlled by the rate of the competing protein:protein interaction. The rate of heterodimerization with apoBCCP controls the holoBirA monomer supply, and the equilibrium constant of homodimerization tunes the bioO occupancy and, consequently, transcription initiation at the biotin operon |CITS: [23896299]|.
The crystal structure of BirA has been determined by X-ray crystallography to a resolution of 2.3 Å |CITS:[1409631]|, and that of a BirA-biotin complex |CITS:[11353844]| has been solved by several research groups.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
BirA Non-Functional   Apo [IPI], [SM] [1], [2]
BirA-bio-5'-AMP Functional Allosteric Holo [IPI], [SM] [1], [2]
Evolutionary Family: BirA
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: birA
  Genome position: 4173082-4174047
  Length: 966 bp / 321 aa
Operon name: murB-birA
TU(s) encoding the TF:
Transcription unit        Promoter
murB-birA
null


Regulon       
Regulated gene(s) bioA, bioB, bioC, bioD, bioF
Multifun term(s) of regulated gene(s)
biotin (5)
Regulated operon(s) bioA, bioBFCD
First gene in the operon(s) bioA, bioB
Simple and complex regulons BirA
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[BirA,-](2)


Transcription factor binding sites (TFBSs) arrangements       

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  BirA-bio-5'-AMP repressor bioAp Sigma70 11.5 -24.5 bioA
attcggtgtaGACTTGTAAACCTAAATCTTTTCAATTTGGTTTACAAGTCgattatgaca
809262 809301 [SM] [3], [4], [5]
  BirA-bio-5'-AMP repressor bioBp Sigma70 -20.5 -62.5 bioB, bioF, bioC, bioD
tgtcataatcGACTTGTAAACCAAATTGAAAAGATTTAGGTTTACAAGTCtacaccgaat
809262 809301 [SM] [3], [4], [5]


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
Promoter-target gene evolutionary conservation


Evidence    

 [IPI] Inferred from physical interaction

 [SM] Site mutation



Reference(s)    

 [1] Weaver LH., Kwon K., Beckett D., Matthews BW., 2001, Corepressor-induced organization and assembly of the biotin repressor: a model for allosteric activation of a transcriptional regulator., Proc Natl Acad Sci U S A. 98(11):6045-50

 [2] Wilson KP., Shewchuk LM., Brennan RG., Otsuka AJ., Matthews BW., 1992, Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains., Proc Natl Acad Sci U S A. 89(19):9257-61

 [3] Cronan JE., 1989, The E. coli bio operon: transcriptional repression by an essential protein modification enzyme., Cell. 58(3):427-9

 [4] Lin KC., Campbell A., Shiuan D., 1991, Binding characteristics of Escherichia coli biotin repressor-operator complex., Biochim Biophys Acta. 1090(3):317-25

 [5] Otsuka A., Abelson J., 1978, The regulatory region of the biotin operon in Escherichia coli., Nature. 276(5689):689-94



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