BIRA_ECOLI
ID BIRA_ECOLI Reviewed; 321 AA.
AC P06709; Q2M8R4;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Bifunctional ligase/repressor BirA {ECO:0000255|HAMAP-Rule:MF_00978};
DE AltName: Full=Biotin operon repressor {ECO:0000255|HAMAP-Rule:MF_00978};
DE AltName: Full=Biotin--[acetyl-CoA-carboxylase] ligase {ECO:0000255|HAMAP-Rule:MF_00978};
DE EC=6.3.4.15 {ECO:0000255|HAMAP-Rule:MF_00978};
DE AltName: Full=Biotin--protein ligase {ECO:0000255|HAMAP-Rule:MF_00978};
DE AltName: Full=Biotin-[acetyl-CoA carboxylase] synthetase {ECO:0000255|HAMAP-Rule:MF_00978};
GN Name=birA {ECO:0000255|HAMAP-Rule:MF_00978}; Synonyms=bioR, dhbB;
GN OrderedLocusNames=b3973, JW3941;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3899863; DOI=10.1016/0378-1119(85)90011-3;
RA Howard P.K., Shaw J., Otsuka A.J.;
RT "Nucleotide sequence of the birA gene encoding the biotin operon repressor
RT and biotin holoenzyme synthetase functions of Escherichia coli.";
RL Gene 35:321-331(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3536662; DOI=10.1016/0378-1119(86)90189-7;
RA Buoncristiani M.R., Howard P.K., Otsuka A.J.;
RT "DNA-binding and enzymatic domains of the bifunctional biotin operon
RT repressor (BirA) of Escherichia coli.";
RL Gene 44:255-261(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=8265357; DOI=10.1093/nar/21.23.5408;
RA Blattner F.R., Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L.;
RT "Analysis of the Escherichia coli genome. IV. DNA sequence of the region
RT from 89.2 to 92.8 minutes.";
RL Nucleic Acids Res. 21:5408-5417(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-76.
RC STRAIN=RDD012;
RX PubMed=1311302; DOI=10.1128/jb.174.5.1690-1693.1992;
RA Pucci M.J., Discotto L.F., Dougherty T.J.;
RT "Cloning and identification of the Escherichia coli murB DNA sequence,
RT which encodes UDP-N-acetylenolpyruvoylglucosamine reductase.";
RL J. Bacteriol. 174:1690-1693(1992).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 226-321.
RX PubMed=1328157; DOI=10.1128/jb.174.20.6411-6417.1992;
RA Song W.-J., Jackowski S.;
RT "Cloning, sequencing, and expression of the pantothenate kinase (coaA) gene
RT of Escherichia coli.";
RL J. Bacteriol. 174:6411-6417(1992).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=6129246; DOI=10.1016/s0021-9258(18)33408-2;
RA Eisenberg M.A., Prakash O., Hsiung S.C.;
RT "Purification and properties of the biotin repressor. A bifunctional
RT protein.";
RL J. Biol. Chem. 257:15167-15173(1982).
RN [9]
RP FUNCTION.
RX PubMed=2667763; DOI=10.1016/0092-8674(89)90421-2;
RA Cronan J.E. Jr.;
RT "The E. coli bio operon: transcriptional repression by an essential protein
RT modification enzyme.";
RL Cell 58:427-429(1989).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8003500; DOI=10.1021/bi00189a041;
RA Xu Y., Beckett D.;
RT "Kinetics of biotinyl-5'-adenylate synthesis catalyzed by the Escherichia
RT coli repressor of biotin biosynthesis and the stability of the enzyme-
RT product complex.";
RL Biochemistry 33:7354-7360(1994).
RN [11]
RP FUNCTION, DNA-BINDING, AND SUBUNIT.
RX PubMed=12527300; DOI=10.1016/s0022-2836(02)01308-6;
RA Streaker E.D., Beckett D.;
RT "Coupling of protein assembly and DNA binding: biotin repressor
RT dimerization precedes biotin operator binding.";
RL J. Mol. Biol. 325:937-948(2003).
RN [12]
RP DOMAIN, AND MUTAGENESIS OF THR-52; GLY-57 AND TYR-58.
RC STRAIN=K12;
RX PubMed=24189073; DOI=10.1074/jbc.m113.525618;
RA Chakravartty V., Cronan J.E.;
RT "The wing of a winged helix-turn-helix transcription factor organizes the
RT active site of BirA, a bifunctional repressor/ligase.";
RL J. Biol. Chem. 288:36029-36039(2013).
RN [13]
RP ACTIVITY REGULATION, SUBUNIT, AND INTERACTION WITH BCCP.
RX PubMed=23896299; DOI=10.1016/j.jmb.2013.07.029;
RA Adikaram P.R., Beckett D.;
RT "Protein:protein interactions in control of a transcriptional switch.";
RL J. Mol. Biol. 425:4584-4594(2013).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH BIOTIN, AND DOMAIN.
RX PubMed=1409631; DOI=10.1073/pnas.89.19.9257;
RA Wilson K.P., Shewchuk L.M., Brennan R.G., Otsuka A.J., Matthews B.W.;
RT "Escherichia coli biotin holoenzyme synthetase/bio repressor crystal
RT structure delineates the biotin- and DNA-binding domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:9257-9261(1992).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH BIOTIN, SUBUNIT, AND
RP DOMAIN.
RX PubMed=11353844; DOI=10.1073/pnas.111128198;
RA Weaver L.H., Kwon K., Beckett D., Matthews B.W.;
RT "Corepressor-induced organization and assembly of the biotin repressor: a
RT model for allosteric activation of a transcriptional regulator.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:6045-6050(2001).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH BIOTINOL-5'-AMP,
RP SUBUNIT, AND DOMAIN.
RX PubMed=16438984; DOI=10.1016/j.jmb.2005.12.066;
RA Wood Z.A., Weaver L.H., Brown P.H., Beckett D., Matthews B.W.;
RT "Co-repressor induced order and biotin repressor dimerization: a case for
RT divergent followed by convergent evolution.";
RL J. Mol. Biol. 357:509-523(2006).
CC -!- FUNCTION: Acts both as a biotin--[acetyl-CoA-carboxylase] ligase and a
CC biotin-operon repressor. In the presence of ATP, BirA activates biotin
CC to form the BirA-biotinyl-5'-adenylate (BirA-bio-5'-AMP or holoBirA)
CC complex. HoloBirA can either transfer the biotinyl moiety to the biotin
CC carboxyl carrier protein (BCCP) subunit of acetyl-CoA carboxylase, or
CC bind to the biotin operator site and inhibit transcription of the
CC operon. {ECO:0000255|HAMAP-Rule:MF_00978, ECO:0000269|PubMed:12527300,
CC ECO:0000269|PubMed:2667763, ECO:0000269|PubMed:6129246,
CC ECO:0000269|PubMed:8003500}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + biotin + L-lysyl-[protein] = AMP + diphosphate + H(+) +
CC N(6)-biotinyl-L-lysyl-[protein]; Xref=Rhea:RHEA:11756, Rhea:RHEA-
CC COMP:9752, Rhea:RHEA-COMP:10505, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29969, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57586, ChEBI:CHEBI:83144, ChEBI:CHEBI:456215;
CC EC=6.3.4.15; Evidence={ECO:0000255|HAMAP-Rule:MF_00978,
CC ECO:0000269|PubMed:6129246, ECO:0000269|PubMed:8003500};
CC -!- ACTIVITY REGULATION: The switch between the enzymatic activity and the
CC repressor activity is regulated by cellular demand for biotin. The
CC switch occurs by swapping of protein interaction partners by holoBirA.
CC In conditions of high biotin demand, holoBirA associates with apoBCCP
CC to transfer biotin. In conditions of low biotin demand, holoBirA
CC dimerizes, binds DNA and represses transcription of the biotin operon.
CC {ECO:0000269|PubMed:23896299}.
CC -!- SUBUNIT: Monomer in solution. Interacts with BCCP. Homodimerizes to
CC bind DNA. Interaction with the corepressor bio-5'-AMP increases
CC dimerization. {ECO:0000269|PubMed:11353844,
CC ECO:0000269|PubMed:12527300, ECO:0000269|PubMed:1409631,
CC ECO:0000269|PubMed:16438984, ECO:0000269|PubMed:23896299,
CC ECO:0000269|PubMed:6129246}.
CC -!- INTERACTION:
CC P06709; P0A761: nanE; NbExp=2; IntAct=EBI-545740, EBI-561432;
CC -!- DOMAIN: Contains an N-terminal helix-turn-helix DNA-binding domain,
CC connected via a linker to the central catalytic domain and the C-
CC terminal domain, which plays roles in dimerization, catalytic function
CC and DNA binding. The N-terminal domain is required for both ligase and
CC repressor activities. It may orient the active site and thereby play an
CC important role in enzymatic activity. {ECO:0000269|PubMed:11353844,
CC ECO:0000269|PubMed:1409631, ECO:0000269|PubMed:16438984,
CC ECO:0000269|PubMed:24189073}.
CC -!- SIMILARITY: Belongs to the biotin--protein ligase family.
CC {ECO:0000255|HAMAP-Rule:MF_00978}.
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DR EMBL; M10123; AAA23520.1; -; Genomic_DNA.
DR EMBL; M15820; AAA23521.1; -; Genomic_DNA.
DR EMBL; L14557; AAA24186.1; -; Genomic_DNA.
DR EMBL; U00006; AAC43075.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76951.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77342.1; -; Genomic_DNA.
DR PIR; B24029; BVECBF.
DR RefSeq; NP_418404.1; NC_000913.3.
DR RefSeq; WP_000654630.1; NZ_SSZK01000084.1.
DR PDB; 1BIA; X-ray; 2.30 A; A=1-321.
DR PDB; 1BIB; X-ray; 2.80 A; A=1-321.
DR PDB; 1HXD; X-ray; 2.40 A; A/B=1-321.
DR PDB; 2EWN; X-ray; 2.80 A; A/B=1-321.
DR PDB; 4WF2; X-ray; 2.31 A; A=1-321.
DR PDBsum; 1BIA; -.
DR PDBsum; 1BIB; -.
DR PDBsum; 1HXD; -.
DR PDBsum; 2EWN; -.
DR PDBsum; 4WF2; -.
DR AlphaFoldDB; P06709; -.
DR SMR; P06709; -.
DR BioGRID; 4263391; 269.
DR DIP; DIP-9224N; -.
DR IntAct; P06709; 7.
DR STRING; 511145.b3973; -.
DR BindingDB; P06709; -.
DR ChEMBL; CHEMBL3559644; -.
DR DrugBank; DB04651; BIOTINOL-5-AMP.
DR MoonProt; P06709; -.
DR jPOST; P06709; -.
DR PaxDb; P06709; -.
DR PRIDE; P06709; -.
DR EnsemblBacteria; AAC76951; AAC76951; b3973.
DR EnsemblBacteria; BAE77342; BAE77342; BAE77342.
DR GeneID; 58463579; -.
DR GeneID; 948469; -.
DR KEGG; ecj:JW3941; -.
DR KEGG; eco:b3973; -.
DR PATRIC; fig|1411691.4.peg.2735; -.
DR EchoBASE; EB0121; -.
DR eggNOG; COG0340; Bacteria.
DR eggNOG; COG1654; Bacteria.
DR HOGENOM; CLU_051096_4_0_6; -.
DR InParanoid; P06709; -.
DR OMA; AVWKHIE; -.
DR PhylomeDB; P06709; -.
DR BioCyc; EcoCyc:BIOTINLIG-MON; -.
DR BioCyc; MetaCyc:BIOTINLIG-MON; -.
DR BRENDA; 6.3.4.15; 2026.
DR EvolutionaryTrace; P06709; -.
DR PRO; PR:P06709; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0017053; C:transcription repressor complex; IDA:CAFA.
DR GO; GO:0005524; F:ATP binding; IMP:CAFA.
DR GO; GO:0009374; F:biotin binding; IDA:CAFA.
DR GO; GO:0004077; F:biotin-[acetyl-CoA-carboxylase] ligase activity; IDA:EcoliWiki.
DR GO; GO:0003677; F:DNA binding; IDA:EcoliWiki.
DR GO; GO:0042803; F:protein homodimerization activity; IMP:CAFA.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IMP:CAFA.
DR GO; GO:0009102; P:biotin biosynthetic process; IMP:EcoliWiki.
DR GO; GO:0006768; P:biotin metabolic process; IMP:CAFA.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-UniRule.
DR CDD; cd16442; BPL; 1.
DR DisProt; DP00349; -.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR HAMAP; MF_00978; Bifunct_BirA; 1.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR030855; Bifunct_BirA.
DR InterPro; IPR004408; Biotin_CoA_COase_ligase.
DR InterPro; IPR004409; Biotin_operon_repress_HTH.
DR InterPro; IPR003142; BPL_C.
DR InterPro; IPR004143; BPL_LPL_catalytic.
DR InterPro; IPR013196; HTH_11.
DR InterPro; IPR008988; Transcriptional_repressor_C.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF02237; BPL_C; 1.
DR Pfam; PF03099; BPL_LplA_LipB; 1.
DR Pfam; PF08279; HTH_11; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF50037; SSF50037; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR TIGRFAMs; TIGR00121; birA_ligase; 1.
DR TIGRFAMs; TIGR00122; birA_repr_reg; 1.
DR PROSITE; PS51733; BPL_LPL_CATALYTIC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Biotin; DNA-binding; Ligase; Nucleotide-binding;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..321
FT /note="Bifunctional ligase/repressor BirA"
FT /id="PRO_0000064932"
FT DOMAIN 67..254
FT /note="BPL/LPL catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01067"
FT DNA_BIND 22..41
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00978"
FT BINDING 89..91
FT /ligand="biotin"
FT /ligand_id="ChEBI:CHEBI:57586"
FT BINDING 112
FT /ligand="biotin"
FT /ligand_id="ChEBI:CHEBI:57586"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00978,
FT ECO:0000269|PubMed:11353844, ECO:0000269|PubMed:1409631"
FT BINDING 116..118
FT /ligand="biotin"
FT /ligand_id="ChEBI:CHEBI:57586"
FT BINDING 183
FT /ligand="biotin"
FT /ligand_id="ChEBI:CHEBI:57586"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00978,
FT ECO:0000269|PubMed:11353844, ECO:0000269|PubMed:1409631"
FT VARIANT 61
FT /note="P -> A (in strain: RDD012)"
FT VARIANT 70
FT /note="K -> E (in strain: RDD012)"
FT MUTAGEN 52
FT /note="T->I: Does not affect repressor activity."
FT /evidence="ECO:0000269|PubMed:24189073"
FT MUTAGEN 52
FT /note="T->S: 5-fold increase of repressor activity.
FT Increases binding to DNA."
FT /evidence="ECO:0000269|PubMed:24189073"
FT MUTAGEN 57
FT /note="G->S: Lack of repressor activity. Does not bind
FT DNA."
FT /evidence="ECO:0000269|PubMed:24189073"
FT MUTAGEN 58
FT /note="Y->F: Lack of repressor activity."
FT /evidence="ECO:0000269|PubMed:24189073"
FT MUTAGEN 58
FT /note="Y->T: Does not affect repressor activity."
FT /evidence="ECO:0000269|PubMed:24189073"
FT HELIX 5..14
FT /evidence="ECO:0007829|PDB:1BIA"
FT HELIX 22..29
FT /evidence="ECO:0007829|PDB:1BIA"
FT HELIX 33..45
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:1BIA"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:1BIA"
FT HELIX 69..74
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:2EWN"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:1BIA"
FT HELIX 90..95
FT /evidence="ECO:0007829|PDB:1BIA"
FT HELIX 96..100
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 106..110
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 129..139
FT /evidence="ECO:0007829|PDB:1BIA"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:2EWN"
FT HELIX 147..163
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:1BIA"
FT TURN 173..175
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 176..179
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 182..192
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:1HXD"
FT STRAND 199..208
FT /evidence="ECO:0007829|PDB:1BIA"
FT TURN 216..218
FT /evidence="ECO:0007829|PDB:2EWN"
FT TURN 226..230
FT /evidence="ECO:0007829|PDB:1BIA"
FT HELIX 235..256
FT /evidence="ECO:0007829|PDB:1BIA"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:1BIA"
FT HELIX 262..268
FT /evidence="ECO:0007829|PDB:1BIA"
FT TURN 270..273
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 274..280
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 283..292
FT /evidence="ECO:0007829|PDB:1BIA"
FT TURN 294..296
FT /evidence="ECO:0007829|PDB:1HXD"
FT STRAND 298..302
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 305..311
FT /evidence="ECO:0007829|PDB:1BIA"
FT STRAND 313..316
FT /evidence="ECO:0007829|PDB:1BIA"
SQ SEQUENCE 321 AA; 35312 MW; B80AEBCEEE1BD2D4 CRC64;
MKDNTVPLKL IALLANGEFH SGEQLGETLG MSRAAINKHI QTLRDWGVDV FTVPGKGYSL
PEPIQLLNAK QILGQLDGGS VAVLPVIDST NQYLLDRIGE LKSGDACIAE YQQAGRGRRG
RKWFSPFGAN LYLSMFWRLE QGPAAAIGLS LVIGIVMAEV LRKLGADKVR VKWPNDLYLQ
DRKLAGILVE LTGKTGDAAQ IVIGAGINMA MRRVEESVVN QGWITLQEAG INLDRNTLAA
MLIRELRAAL ELFEQEGLAP YLSRWEKLDN FINRPVKLII GDKEIFGISR GIDKQGALLL
EQDGIIKPWM GGEISLRSAE K