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P06709 (BIRA_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bifunctional ligase/repressor BirA
Alternative name(s):
Biotin operon repressor
Biotin--[acetyl-CoA-carboxylase] ligase
EC=6.3.4.15
Biotin--protein ligase
Biotin-[acetyl-CoA carboxylase] synthetase
Gene names
Name:birA
Synonyms:bioR, dhbB
Ordered Locus Names:b3973, JW3941
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length321 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts both as a biotin--[acetyl-CoA-carboxylase] ligase and a biotin-operon repressor. In the presence of ATP, BirA activates biotin to form the BirA-biotinyl-5'-adenylate (BirA-bio-5'-AMP or holoBirA) complex. HoloBirA can either transfer the biotinyl moiety to the biotin carboxyl carrier protein (BCCP) subunit of acetyl-CoA carboxylase, or bind to the biotin operator site and inhibit transcription of the operon. Ref.8 Ref.9 Ref.10 Ref.11

Catalytic activity

ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] = AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)]. Ref.8 Ref.10

Enzyme regulation

The switch between the enzymatic activity and the repressor activity is regulated by cellular demand for biotin. The switch occurs by swapping of protein interaction partners by holoBirA. In conditions of high biotin demand, holoBirA associates with apoBCCP to transfer biotin. In conditions of low biotin demand, holoBirA dimerizes, binds DNA and represses transcription of the biotin operon. Ref.13

Subunit structure

Monomer in solution. Interacts with BCCP. Homodimerizes to bind DNA. Interaction with the corepressor bio-5'-AMP increases dimerization. Ref.8 Ref.11 Ref.13 Ref.15 Ref.16

Domain

Contains an N-terminal helix-turn-helix DNA-binding domain, connected via a linker to the central catalytic domain and the C-terminal domain, which plays roles in dimerization, catalytic function and DNA binding. The N-terminal domain is required for both ligase and repressor activities. It may orient the active site and thereby play an important role in enzymatic activity. Ref.12 Ref.14 Ref.15 Ref.16

Sequence similarities

Belongs to the biotin--protein ligase family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 321321Bifunctional ligase/repressor BirA HAMAP-Rule MF_00978
PRO_0000064932

Regions

DNA binding22 – 4120H-T-H motif Ref.11
Region89 – 913Biotin binding HAMAP-Rule MF_00978
Region116 – 1183Biotin binding HAMAP-Rule MF_00978

Sites

Binding site1121Biotin
Binding site1831Biotin

Natural variations

Natural variant611P → A in strain: RDD012.
Natural variant701K → E in strain: RDD012.

Experimental info

Mutagenesis521T → I: Does not affect repressor activity. Ref.12
Mutagenesis521T → S: 5-fold increase of repressor activity. Increases binding to DNA. Ref.12
Mutagenesis571G → S: Lack of repressor activity. Does not bind DNA. Ref.12
Mutagenesis581Y → F: Lack of repressor activity. Ref.12
Mutagenesis581Y → T: Does not affect repressor activity. Ref.12

Secondary structure

.............................................................. 321
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P06709 [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: B80AEBCEEE1BD2D4

FASTA32135,312
        10         20         30         40         50         60 
MKDNTVPLKL IALLANGEFH SGEQLGETLG MSRAAINKHI QTLRDWGVDV FTVPGKGYSL 

        70         80         90        100        110        120 
PEPIQLLNAK QILGQLDGGS VAVLPVIDST NQYLLDRIGE LKSGDACIAE YQQAGRGRRG 

       130        140        150        160        170        180 
RKWFSPFGAN LYLSMFWRLE QGPAAAIGLS LVIGIVMAEV LRKLGADKVR VKWPNDLYLQ 

       190        200        210        220        230        240 
DRKLAGILVE LTGKTGDAAQ IVIGAGINMA MRRVEESVVN QGWITLQEAG INLDRNTLAA 

       250        260        270        280        290        300 
MLIRELRAAL ELFEQEGLAP YLSRWEKLDN FINRPVKLII GDKEIFGISR GIDKQGALLL 

       310        320 
EQDGIIKPWM GGEISLRSAE K 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of the birA gene encoding the biotin operon repressor and biotin holoenzyme synthetase functions of Escherichia coli."
Howard P.K., Shaw J., Otsuka A.J.
Gene 35:321-331(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"DNA-binding and enzymatic domains of the bifunctional biotin operon repressor (BirA) of Escherichia coli."
Buoncristiani M.R., Howard P.K., Otsuka A.J.
Gene 44:255-261(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes."
Blattner F.R., Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L.
Nucleic Acids Res. 21:5408-5417(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[4]"The complete genome sequence of Escherichia coli K-12."
Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y.
Science 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[5]"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[6]"Cloning and identification of the Escherichia coli murB DNA sequence, which encodes UDP-N-acetylenolpyruvoylglucosamine reductase."
Pucci M.J., Discotto L.F., Dougherty T.J.
J. Bacteriol. 174:1690-1693(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-76.
Strain: RDD012.
[7]"Cloning, sequencing, and expression of the pantothenate kinase (coaA) gene of Escherichia coli."
Song W.-J., Jackowski S.
J. Bacteriol. 174:6411-6417(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 226-321.
[8]"Purification and properties of the biotin repressor. A bifunctional protein."
Eisenberg M.A., Prakash O., Hsiung S.C.
J. Biol. Chem. 257:15167-15173(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBUNIT.
[9]"The E. coli bio operon: transcriptional repression by an essential protein modification enzyme."
Cronan J.E. Jr.
Cell 58:427-429(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Kinetics of biotinyl-5'-adenylate synthesis catalyzed by the Escherichia coli repressor of biotin biosynthesis and the stability of the enzyme-product complex."
Xu Y., Beckett D.
Biochemistry 33:7354-7360(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY.
[11]"Coupling of protein assembly and DNA binding: biotin repressor dimerization precedes biotin operator binding."
Streaker E.D., Beckett D.
J. Mol. Biol. 325:937-948(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING, SUBUNIT.
[12]"The wing of a winged helix-turn-helix transcription factor organizes the active site of BirA, a bifunctional repressor/ligase."
Chakravartty V., Cronan J.E.
J. Biol. Chem. 288:36029-36039(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN, MUTAGENESIS OF THR-52; GLY-57 AND TYR-58.
Strain: K12.
[13]"Protein:protein interactions in control of a transcriptional switch."
Adikaram P.R., Beckett D.
J. Mol. Biol. 425:4584-4594(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, SUBUNIT, INTERACTION WITH BCCP.
[14]"Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains."
Wilson K.P., Shewchuk L.M., Brennan R.G., Otsuka A.J., Matthews B.W.
Proc. Natl. Acad. Sci. U.S.A. 89:9257-9261(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH BIOTIN, DOMAIN.
[15]"Corepressor-induced organization and assembly of the biotin repressor: a model for allosteric activation of a transcriptional regulator."
Weaver L.H., Kwon K., Beckett D., Matthews B.W.
Proc. Natl. Acad. Sci. U.S.A. 98:6045-6050(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH BIOTIN, SUBUNIT, DOMAIN.
[16]"Co-repressor induced order and biotin repressor dimerization: a case for divergent followed by convergent evolution."
Wood Z.A., Weaver L.H., Brown P.H., Beckett D., Matthews B.W.
J. Mol. Biol. 357:509-523(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH BIOTINOL-5'-AMP, SUBUNIT, DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M10123 Genomic DNA. Translation: AAA23520.1.
M15820 Genomic DNA. Translation: AAA23521.1.
L14557 Genomic DNA. Translation: AAA24186.1.
U00006 Genomic DNA. Translation: AAC43075.1.
U00096 Genomic DNA. Translation: AAC76951.1.
AP009048 Genomic DNA. Translation: BAE77342.1.
PIRBVECBF. B24029.
RefSeqNP_418404.1. NC_000913.3.
YP_491483.1. NC_007779.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BIAX-ray2.30A1-321[»]
1BIBX-ray2.80A1-321[»]
1HXDX-ray2.40A/B1-321[»]
1K67model-A65-317[»]
2EWNX-ray2.80A/B1-321[»]
DisProtDP00349.
ProteinModelPortalP06709.
SMRP06709. Positions 3-320.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-9224N.
IntActP06709. 7 interactions.
MINTMINT-1254106.
STRING511145.b3973.

Proteomic databases

PaxDbP06709.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC76951; AAC76951; b3973.
BAE77342; BAE77342; BAE77342.
GeneID12934397.
948469.
KEGGecj:Y75_p3219.
eco:b3973.
PATRIC32123467. VBIEscCol129921_4090.

Organism-specific databases

EchoBASEEB0121.
EcoGeneEG10123. birA.

Phylogenomic databases

eggNOGCOG0340.
HOGENOMHOG000041812.
KOK03524.
OMAADVCHVV.
OrthoDBEOG6DNTBX.
PhylomeDBP06709.

Enzyme and pathway databases

BioCycEcoCyc:BIOTINLIG-MONOMER.
ECOL316407:JW3941-MONOMER.
MetaCyc:BIOTINLIG-MONOMER.

Gene expression databases

GenevestigatorP06709.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
HAMAPMF_00978. Bifunct_BirA.
InterProIPR004408. Biotin_CoA_COase_ligase.
IPR004409. Biotin_operon_repress_HTH.
IPR003142. BPL_C.
IPR004143. BPL_LipA_LipB.
IPR013196. HTH_11.
IPR008988. Transcriptional_repressor_C.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERPTHR12835. PTHR12835. 1 hit.
PfamPF02237. BPL_C. 1 hit.
PF03099. BPL_LplA_LipB. 1 hit.
PF08279. HTH_11. 1 hit.
[Graphical view]
SUPFAMSSF50037. SSF50037. 1 hit.
TIGRFAMsTIGR00121. birA_ligase. 1 hit.
TIGR00122. birA_repr_reg. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP06709.
PROP06709.

Entry information

Entry nameBIRA_ECOLI
AccessionPrimary (citable) accession number: P06709
Secondary accession number(s): Q2M8R4
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: May 14, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene