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BirA DNA-binding transcriptional repressor

Synonyms: BirA-biotinyl-5'-adenylate, BirA
Summary:
BirA is a bifunctional protein that exhibits biotin ligase activity and also acts as the DNA binding transcriptional repressor of the biotin operon []. The effector of BirA transcriptional repression activity, biotinyl-5'-adenylate (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 [6]. BirA is observed to be predominantly monomeric in solution [], with some minor multimeric species observed []. BirA binds as a dimer to its 40 bp DNA site, the biotin operator [4]. An additional, low-affinity BirA DNA binding site has been identified [].
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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 [SM] [1]
BirA-biotinyl-5'-adenylate Functional Allosteric Holo [HIFS], [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 regulation    


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-biotinyl-5'-adenylate repressor bioAp Sigma70 11.5 -25.0 bioA
tgtcataatcGACTTGTAAACCAAATTGAAAAGATTTAGGTTTACAAGTCtacaccgaat
809262 809302 [SM] [3], [4], [5]
  BirA-biotinyl-5'-adenylate repressor bioBp Sigma70 -20.5 -62.0 bioB, bioF, bioC, bioD
attcggtgtaGACTTGTAAACCTAAATCTTTTCAATTTGGTTTACAAGTCgattatgaca
809262 809302 [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    

 [SM] Site mutation

 [HIFS] Human inference of function from sequence

 [IPI] Inferred from physical interaction



Reference(s)    

 [1] 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

 [2] Buoncristiani MR., Howard PK., Otsuka AJ., 1986, DNA-binding and enzymatic domains of the bifunctional biotin operon repressor (BirA) of Escherichia coli., Gene 44(2-3):255-61

 [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

 [6] Beckett D., 1998, Energetic methods to study bifunctional biotin operon repressor., Methods Enzymol 295:424-50

 [7] Streaker ED., Beckett D., 1999, Ligand-linked structural changes in the Escherichia coli biotin repressor: the significance of surface loops for binding and allostery., J Mol Biol 292(3):619-32

 [8] Kwon K., Streaker ED., Ruparelia S., Beckett D., 2000, Multiple disordered loops function in corepressor-induced dimerization of the biotin repressor., J Mol Biol 304(5):821-33

 [9] Howard PK., Shaw J., Otsuka AJ., 1985, Nucleotide sequence of the birA gene encoding the biotin operon repressor and biotin holoenzyme synthetase functions of Escherichia coli., Gene 35(3):321-31

 [10] Campbell A., Chang R., Barker D., Ketner G., 1980, Biotin regulatory (bir) mutations of Escherichia coli., J Bacteriol 142(3):1025-8

 [11] Eisenburg MA., Mee B., Prakash O., Eisenburg MR., 1975, Properties of alpha-dehydrobiotin-resistant mutants of Escherichia coli K-12., J Bacteriol 122(1):66-72

 [12] Reche PA., 2000, Lipoylating and biotinylating enzymes contain a homologous catalytic module., Protein Sci 9(10):1922-9



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