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BirA DNA-binding transcriptional repressor

Synonyms: BirA, BirA-biotinyl-5'-adenylate
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 [5]. The enzymatic functions include the synthesis of the enzyme-bound biotinyl-5'-adenylate (bio-5'-AMP), and the transfer of the biotin from the adenylate to a lysine residue of the biotin carboxyl carrier protein (BCCP) of the acetyl-CoA-carboxylase. The transfer reaction results in the active form of acetyl-CoA-carboxylase. Alternatively, as a regulator, the enzyme-bound to bio-5'-AMP represses transcription of the biotin biosynthetic operon by binding to the biotin operator sequence [2]. BirA is observed to be predominantly monomeric in solution [], with some minor multimeric species observed [].
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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 nd nd
BirA-biotinyl-5'-adenylate Functional Allosteric Holo nd [1]
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

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)

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 -24.5 bioA
809262 809302 [SM] [2], [3], [4]
  BirA-biotinyl-5'-adenylate repressor bioBp Sigma70 -20.5 -62.5 bioB, bioF, bioC, bioD
809262 809302 [SM] [2], [3], [4]

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


 [SM] Site mutation


 [1] 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

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

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

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

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

 [6] Prakash O., Eisenberg MA., 1978, In vitro synthesis and and regulation of the biotin enzymes of Escherichia coli K-12., J Bacteriol 134(3):1002-12

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

 [8] Campbell A., Del Campillo-Campbell A., Chang R., 1972, A mutant of Escherichia coli that requires high concentrations of biotin., Proc Natl Acad Sci U S A 69(3):676-80

 [9] Pai CH., 1972, Mutant of Escherichia coli with derepressed levels of the biotin biosynthetic enzymes., J Bacteriol 112(3):1280-7

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

 [11] 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

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

 [13] Pai CH., 1973, Biotin uptake in biotin regulatory mutant of Escherichia coli., J Bacteriol 116(1):494-6

 [14] Eisenberg MA., 1973, Biotin: biogenesis, transport, and their regulation., Adv Enzymol Relat Areas Mol Biol 38:317-72