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Protein

Bifunctional ligase/repressor BirA

Gene

birA

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.UniRule annotation4 Publications

Catalytic activityi

ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] = AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)].UniRule annotation2 Publications

Enzyme regulationi

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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei112 – 1121BiotinUniRule annotation2 Publications
Binding sitei183 – 1831BiotinUniRule annotation2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi22 – 4120H-T-H motifUniRule annotationAdd
BLAST

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. biotin-[acetyl-CoA-carboxylase] ligase activity Source: EcoliWiki
  3. DNA binding Source: EcoliWiki

GO - Biological processi

  1. biotin biosynthetic process Source: EcoliWiki
  2. protein biotinylation Source: CACAO
  3. regulation of transcription, DNA-templated Source: UniProtKB-KW
  4. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Ligase, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Biotin, DNA-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciEcoCyc:BIOTINLIG-MONOMER.
ECOL316407:JW3941-MONOMER.
MetaCyc:BIOTINLIG-MONOMER.
BRENDAi6.3.4.15. 2026.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional ligase/repressor BirAUniRule annotation
Alternative name(s):
Biotin operon repressorUniRule annotation
Biotin--[acetyl-CoA-carboxylase] ligaseUniRule annotation (EC:6.3.4.15UniRule annotation)
Biotin--protein ligaseUniRule annotation
Biotin-[acetyl-CoA carboxylase] synthetaseUniRule annotation
Gene namesi
Name:birAUniRule annotation
Synonyms:bioR, dhbB
Ordered Locus Names:b3973, JW3941
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
ProteomesiUP000000318 Componenti: Chromosome UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10123. birA.

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi52 – 521T → I: Does not affect repressor activity. 1 Publication
Mutagenesisi52 – 521T → S: 5-fold increase of repressor activity. Increases binding to DNA. 1 Publication
Mutagenesisi57 – 571G → S: Lack of repressor activity. Does not bind DNA. 1 Publication
Mutagenesisi58 – 581Y → F: Lack of repressor activity. 1 Publication
Mutagenesisi58 – 581Y → T: Does not affect repressor activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 321321Bifunctional ligase/repressor BirAPRO_0000064932Add
BLAST

Proteomic databases

PaxDbiP06709.

Expressioni

Gene expression databases

GenevestigatoriP06709.

Interactioni

Subunit structurei

Monomer in solution. Interacts with BCCP. Homodimerizes to bind DNA. Interaction with the corepressor bio-5'-AMP increases dimerization.6 Publications

Protein-protein interaction databases

DIPiDIP-9224N.
IntActiP06709. 7 interactions.
MINTiMINT-1254106.
STRINGi511145.b3973.

Structurei

Secondary structure

1
321
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi5 – 1410Combined sources
Helixi22 – 298Combined sources
Helixi33 – 4513Combined sources
Beta strandi51 – 533Combined sources
Turni54 – 563Combined sources
Beta strandi57 – 593Combined sources
Helixi69 – 746Combined sources
Beta strandi76 – 794Combined sources
Beta strandi81 – 833Combined sources
Beta strandi85 – 884Combined sources
Helixi90 – 956Combined sources
Helixi96 – 1005Combined sources
Beta strandi106 – 1105Combined sources
Beta strandi129 – 13911Combined sources
Helixi143 – 1453Combined sources
Helixi147 – 16317Combined sources
Beta strandi170 – 1723Combined sources
Turni173 – 1753Combined sources
Beta strandi176 – 1794Combined sources
Beta strandi182 – 19211Combined sources
Beta strandi195 – 1973Combined sources
Beta strandi199 – 20810Combined sources
Turni216 – 2183Combined sources
Turni226 – 2305Combined sources
Helixi235 – 25622Combined sources
Helixi259 – 2613Combined sources
Helixi262 – 2687Combined sources
Turni270 – 2734Combined sources
Beta strandi274 – 2807Combined sources
Beta strandi283 – 29210Combined sources
Turni294 – 2963Combined sources
Beta strandi298 – 3025Combined sources
Beta strandi305 – 3117Combined sources
Beta strandi313 – 3164Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BIAX-ray2.30A1-321[»]
1BIBX-ray2.80A1-321[»]
1HXDX-ray2.40A/B1-321[»]
1K67model-A65-317[»]
2EWNX-ray2.80A/B1-321[»]
4WF2X-ray2.31A1-321[»]
DisProtiDP00349.
ProteinModelPortaliP06709.
SMRiP06709. Positions 3-320.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06709.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini67 – 254188BPL/LPL catalyticPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni89 – 913Biotin binding
Regioni116 – 1183Biotin binding

Domaini

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.4 Publications

Sequence similaritiesi

Belongs to the biotin--protein ligase family.UniRule annotation
Contains 1 BPL/LPL catalytic domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0340.
HOGENOMiHOG000041812.
InParanoidiP06709.
KOiK03524.
OMAiIYSADIE.
OrthoDBiEOG6DNTBX.
PhylomeDBiP06709.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
HAMAPiMF_00978. Bifunct_BirA.
InterProiIPR004408. 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]
PANTHERiPTHR12835. PTHR12835. 1 hit.
PfamiPF02237. BPL_C. 1 hit.
PF03099. BPL_LplA_LipB. 1 hit.
PF08279. HTH_11. 1 hit.
[Graphical view]
SUPFAMiSSF50037. SSF50037. 1 hit.
TIGRFAMsiTIGR00121. birA_ligase. 1 hit.
TIGR00122. birA_repr_reg. 1 hit.
PROSITEiPS51733. BPL_LPL_CATALYTIC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P06709-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKDNTVPLKL IALLANGEFH SGEQLGETLG MSRAAINKHI QTLRDWGVDV
60 70 80 90 100
FTVPGKGYSL PEPIQLLNAK QILGQLDGGS VAVLPVIDST NQYLLDRIGE
110 120 130 140 150
LKSGDACIAE YQQAGRGRRG RKWFSPFGAN LYLSMFWRLE QGPAAAIGLS
160 170 180 190 200
LVIGIVMAEV LRKLGADKVR VKWPNDLYLQ DRKLAGILVE LTGKTGDAAQ
210 220 230 240 250
IVIGAGINMA MRRVEESVVN QGWITLQEAG INLDRNTLAA MLIRELRAAL
260 270 280 290 300
ELFEQEGLAP YLSRWEKLDN FINRPVKLII GDKEIFGISR GIDKQGALLL
310 320
EQDGIIKPWM GGEISLRSAE K
Length:321
Mass (Da):35,312
Last modified:January 1, 1988 - v1
Checksum:iB80AEBCEEE1BD2D4
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti61 – 611P → A in strain: RDD012.
Natural varianti70 – 701K → E in strain: RDD012.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiB24029. BVECBF.
RefSeqiNP_418404.1. NC_000913.3.
YP_491483.1. NC_007779.1.

Genome annotation databases

EnsemblBacteriaiAAC76951; AAC76951; b3973.
BAE77342; BAE77342; BAE77342.
GeneIDi12934397.
948469.
KEGGiecj:Y75_p3219.
eco:b3973.
PATRICi32123467. VBIEscCol129921_4090.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiB24029. BVECBF.
RefSeqiNP_418404.1. NC_000913.3.
YP_491483.1. NC_007779.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BIAX-ray2.30A1-321[»]
1BIBX-ray2.80A1-321[»]
1HXDX-ray2.40A/B1-321[»]
1K67model-A65-317[»]
2EWNX-ray2.80A/B1-321[»]
4WF2X-ray2.31A1-321[»]
DisProtiDP00349.
ProteinModelPortaliP06709.
SMRiP06709. Positions 3-320.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-9224N.
IntActiP06709. 7 interactions.
MINTiMINT-1254106.
STRINGi511145.b3973.

Proteomic databases

PaxDbiP06709.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC76951; AAC76951; b3973.
BAE77342; BAE77342; BAE77342.
GeneIDi12934397.
948469.
KEGGiecj:Y75_p3219.
eco:b3973.
PATRICi32123467. VBIEscCol129921_4090.

Organism-specific databases

EchoBASEiEB0121.
EcoGeneiEG10123. birA.

Phylogenomic databases

eggNOGiCOG0340.
HOGENOMiHOG000041812.
InParanoidiP06709.
KOiK03524.
OMAiIYSADIE.
OrthoDBiEOG6DNTBX.
PhylomeDBiP06709.

Enzyme and pathway databases

BioCyciEcoCyc:BIOTINLIG-MONOMER.
ECOL316407:JW3941-MONOMER.
MetaCyc:BIOTINLIG-MONOMER.
BRENDAi6.3.4.15. 2026.

Miscellaneous databases

EvolutionaryTraceiP06709.
PROiP06709.

Gene expression databases

GenevestigatoriP06709.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
HAMAPiMF_00978. Bifunct_BirA.
InterProiIPR004408. 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]
PANTHERiPTHR12835. PTHR12835. 1 hit.
PfamiPF02237. BPL_C. 1 hit.
PF03099. BPL_LplA_LipB. 1 hit.
PF08279. HTH_11. 1 hit.
[Graphical view]
SUPFAMiSSF50037. SSF50037. 1 hit.
TIGRFAMsiTIGR00121. birA_ligase. 1 hit.
TIGR00122. birA_repr_reg. 1 hit.
PROSITEiPS51733. BPL_LPL_CATALYTIC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1984) [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(1985) [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(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  4. 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(2005) [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(1991) [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(1991) [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(1981) [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(1988) [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(1993) [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(2002) [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(2012) [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(2012) [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(1991) [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(2000) [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(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH BIOTINOL-5'-AMP, SUBUNIT, DOMAIN.

Entry informationi

Entry nameiBIRA_ECOLI
AccessioniPrimary (citable) accession number: P06709
Secondary accession number(s): Q2M8R4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: April 1, 2015
This is version 148 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.