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Information on EC 6.3.4.15 - biotin-[biotin carboxyl-carrier protein] ligase and Organism(s) Homo sapiens

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IUBMB Comments
The enzyme biotinylates a biotin carboxyl-carrier protein that is part of an acetyl-CoA carboxylase complex, enabling its subsequent carboxylation by EC 6.3.4.14, biotin carboxylase. The carboxyl group is eventually transferred to acetyl-CoA by EC 2.1.3.15, acetyl-CoA carboxytransferase. In some organisms the carrier protein is part of EC 6.4.1.2, acetyl-CoA carboxylase.
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This record set is specific for:
Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Synonyms
biotin ligase, bira protein, biotin-protein ligase, biotin holoenzyme synthetase, bacterial bira biotin ligase, biotin acetyl-coa carboxylase ligase, biotin:apocarboxylase ligase, holocarboxylase synthetase 1, group i biotin protein ligase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acetyl CoA holocarboxylase synthetase
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Acetyl coenzyme A holocarboxylase synthetase
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Biotin holoenzyme synthetase
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biotin ligase
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biotin protein ligase
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Biotin--protein ligase
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Biotin-[acetyl coenzyme A carboxylase] synthetase
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Biotin-[acetyl-CoA carboxylase] synthetase
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Biotin:apocarboxylase ligase
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Holocarboxylase synthetase
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Synthetase, biotin-[acetyl coenzyme A carboxylase]
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
amination
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
biotin:apo-[carboxyl-carrier protein] ligase (AMP-forming)
The enzyme biotinylates a biotin carboxyl-carrier protein that is part of an acetyl-CoA carboxylase complex, enabling its subsequent carboxylation by EC 6.3.4.14, biotin carboxylase. The carboxyl group is eventually transferred to acetyl-CoA by EC 2.1.3.15, acetyl-CoA carboxytransferase. In some organisms the carrier protein is part of EC 6.4.1.2, acetyl-CoA carboxylase.
CAS REGISTRY NUMBER
COMMENTARY hide
37340-95-7
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + biotin + apo-[acetyl-CoA carboxylase 1]
AMP + diphosphate + acetyl-CoA carboxylase 1
show the reaction diagram
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cytoplasmic acetyl-CoA carboxylase isozyme
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-
?
ATP + biotin + apo-[acetyl-CoA carboxylase 2]
AMP + diphosphate + acetyl-CoA carboxylase 2
show the reaction diagram
ATP + biotin + apo-[acetyl-CoA carboxylase]
AMP + diphosphate + acetyl-CoA carboxylase
show the reaction diagram
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-
-
-
?
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)]
AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)]
show the reaction diagram
ATP + biotin + apo-[biotin carboxyl carrier protein]
AMP + diphosphate + biotin carboxyl carrier protein
show the reaction diagram
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i.e. BCCP, substrate is the recombinantly expressed His-tagged biotinoyl domain, BCCP87, of Escherichia coli BCCP, binding pattern, overview
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-
?
ATP + biotin + apo-[propionyl-CoA carboxylase]
AMP + diphosphate + propionyl-CoA carboxylase
show the reaction diagram
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-
-
-
?
ATP + biotin + apocarboxylase
AMP + diphosphate + holocarboxylase
show the reaction diagram
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?
ATP + biotin + protein p67
AMP + diphosphate + biotinyl-protein p67
show the reaction diagram
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-
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?
additional information
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + biotin + apo-[acetyl-CoA carboxylase 1]
AMP + diphosphate + acetyl-CoA carboxylase 1
show the reaction diagram
-
cytoplasmic acetyl-CoA carboxylase isozyme
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-
?
ATP + biotin + apo-[acetyl-CoA carboxylase 2]
AMP + diphosphate + acetyl-CoA carboxylase 2
show the reaction diagram
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mitochondrial acetyl-CoA carboxylase isozyme
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-
?
ATP + biotin + apo-[acetyl-CoA carboxylase]
AMP + diphosphate + acetyl-CoA carboxylase
show the reaction diagram
-
-
-
-
?
ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)]
AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)]
show the reaction diagram
ATP + biotin + apocarboxylase
AMP + diphosphate + holocarboxylase
show the reaction diagram
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-
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?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
biotin
additional information
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no activity with biotin analogues desthiobiotin azide, cis-propargyl biotin, trans-propargyl biotin, iminobiotin, diaminobiotin, nitrobenzoxadiazole gamma-butyric acid, iodouracil valeric acid, thiouracil valeric acid
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.26
biotin
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reaction with ATP + apo-carboxyl carrier protein, a subunit of acetyl-CoA carboxylase from E. coli
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.3
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assay at
8
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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lung fibroblasts, quantitative determination of HCS in wild-type IMR-90 fibroblasts and in those recombinantly overexpressing human telomerase, evaluation as a cell model for investigation of HCS in epigenetic regulation, histone biotinylation in aging cells, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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the longer Met58 isoform
Manually annotated by BRENDA team
additional information
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isozyme subcellular localization, immunofluorescence study, overview
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
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HCS is responsible for attaching biotin onto the biotin-dependent enzymes that reside in the cytoplasm and mitochondria
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
BPL1_HUMAN
726
0
80760
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
265000
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acetyl-CoA carboxylase-1
82000
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SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D571N
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naturally occuring mutation, important in positioning K579 in the AMP binding site
D615Y
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naturally occuring mutation in the loop between alpha3 and beta6 that cover AMP, may coordinate oxygens of the AMP phosphate
D634Y
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naturally occuring mutation of a solvent exposed residue, distal to active site on alpha4 and alpha5, respectively
D715G
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naturally occuring mutation on beta9, may be involved in capping and stabilising the catalytic domain structure
G518E
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naturally occuring mutation close to the active site and part of the ligand-binding loop, the mutation may not allow as much flexibility of this loop. As part of the hydrophobic pocket, making this polar residue would perturb biotin binding
G581S
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naturally occuring mutation of a residue involved in hydrophobic interactions with biotin in the binding pocket
G582R
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naturally occuring mutation of a residue involved in hydrophobic interactions with biotin in the binding pocket
L470S
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naturally occuring mutation in an unstructured loop distal to the ligand-binding site
R508W/N511K
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naturally occuring mutation of a residue critical in loop covering the ligand-binding site. R508 co-ordinates to the backbone carbonyl N712 to form a salt bridge, removing this would result in a more flexible loop, analogous to EcBPL R118 and R121 that co-ordinate oxygens within the AMP phosphate group
T462I
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naturally occuring mutation in an unstructured loop distal to the ligand-binding site
V547G
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naturally occuring mutation of a buried hydrophobic residue in alpha2 that reside near the AMP-binding beta5 strand
V550M
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naturally occuring mutation of a buried hydrophobic residue in alpha2 that reside near the AMP-binding beta5 strand
Y456C
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naturally occuring mutation in an unstructured loop distal to the ligand-binding site
additional information
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HCS mutants with deletions up to Ala235 or Thr266 still show catalytic activity and can complement an enzyme-deficient Escherichia coli birA- strain. Enzyme deficiency can cause symptoms like ketoacidosis, feeding difficulties, hypotonia, seizures, developmental delay and dermal abnormalities such as rashes, dryness of the skin and alopecia, multiple carboxylase deficiency is caused by a lack of activity of the biotin-dependent enzymes, phenotypes, overview. Molecular modelling of mutations causing HCS deficiency, detailed overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from Escherichia coli, the human enzyme degrades significantly during isolation
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recombinant human HCS from Hi5 insect cells by nickel affinity chromatography, anion exchange chromatography, and gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cross-species activity of BPLs permitts functional cloning of the cDNA for human BPL through genetic complementation with a conditional lethal birA? strain of Escherichia coli
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expression of HCS in Spodoptera frugiperda Sf9 cells and in Hi5 insect cells using the baculovirus transfection system
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overexpression in Escherichia coli
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
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biotinylation of apo-carboxyl carrier protein, a subunit of acetyl-CoA carboxylase from E. coli is a sensitive and convenient assay method for biotin-[acetyl-CoA-carboxylase] ligase
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Dupuis, L.; Leon-del Rio, A.; Leclerc, D.; Campeau, E.; Sweetman, L.; Saudubray, J.M.; Herman, G.; Gibson, K.M.; Gravel, R.A.
Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency
Hum. Mol. Genet.
5
1011-1016
1996
Homo sapiens
Manually annotated by BRENDA team
Landman, A.D.; Dakshinamurti, K.
Enzymatic diagnosis of holocarboxylase synthetase deficiency using apo-carboxyl carrier protein as a substrate
Clin. Chim. Acta
251
41-52
1996
Homo sapiens
Manually annotated by BRENDA team
Gralla, M.; Camporeale, G.; Zempleni, J.
Holocarboxylase synthetase regulates expression of biotin transporters by chromatin remodeling events at the SMVT locus
J. Nutr. Biochem.
19
400-408
2008
Homo sapiens
Manually annotated by BRENDA team
Pendini, N.R.; Bailey, L.M.; Booker, G.W.; Wilce, M.C.; Wallace, J.C.; Polyak, S.W.
Microbial biotin protein ligases aid in understanding holocarboxylase synthetase deficiency
Biochim. Biophys. Acta
1784
973-982
2008
Escherichia coli (P06709), Homo sapiens, Pyrococcus horikoshii, Pyrococcus horikoshii OT-3, Saccharomyces cerevisiae
Manually annotated by BRENDA team
Slavoff, S.A.; Chen, I.; Choi, Y.; Ting, A.Y.
Expanding the substrate tolerance of biotin ligase through exploration of enzymes from diverse species
J. Am. Chem. Soc.
130
1160-1162
2008
Bacillus subtilis, Leuconostoc mesenteroides, Saccharomyces cerevisiae, Escherichia coli, Giardia intestinalis, Homo sapiens, Methanocaldococcus jannaschii, Cutibacterium acnes, Pyrococcus horikoshii, Trypanosoma cruzi
Manually annotated by BRENDA team
Bailey, L.M.; Wallace, J.C.; Polyak, S.W.
Holocarboxylase synthetase: correlation of protein localisation with biological function
Arch. Biochem. Biophys.
496
45-52
2010
Homo sapiens
Manually annotated by BRENDA team
Lee, C.K.; Cheong, C.; Jeon, Y.H.
Substrate recognition characteristics of human holocarboxylase synthetase for biotin ligation
Biochem. Biophys. Res. Commun.
391
455-460
2010
Homo sapiens
Manually annotated by BRENDA team
Zempleni, J.; Wijeratne, S.S.; Hassan, Y.I.
Biotin
Biofactors
35
36-46
2009
Homo sapiens
Manually annotated by BRENDA team
Yokoi, K.; Ito, T.; Maeda, Y.; Nakajima, Y.; Kurono, Y.; Sugiyama, N.; Togari, H.
A case of holocarboxylase synthetase deficiency with insufficient response to prenatal biotin therapy
Brain Dev.
31
775-778
2009
Homo sapiens
Manually annotated by BRENDA team
Lee, C.K.; Cheong, C.; Jeon, Y.H.
The N-terminal domain of human holocarboxylase synthetase facilitates biotinylation via direct interaction with the substrate protein
FEBS Lett.
584
675-680
2010
Homo sapiens
Manually annotated by BRENDA team
Wijeratne, S.S.; Camporeale, G.; Zempleni, J.
K12-biotinylated histone H4 is enriched in telomeric repeats from human lung IMR-90 fibroblasts
J. Nutr. Biochem.
21
310-316
2010
Homo sapiens
Manually annotated by BRENDA team