ArticleProceedings of the National Academy of Sciences of the United States of America1995
Isolation of a cDNA encoding human holocarboxylase synthetase by functional complementation of a biotin auxotroph of Escherichia coli.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 108 citations in OpenAlex.
- Biotin Induces Inactive Chromosome X Reactivation and Corrects Physiopathological Alterations in Beta-Propeller-Protein-Associated Neurodegeneration.International journal of molecular sciences · 2025Article
- Review
- Biotin protein ligase as you like it: Either extraordinarily specific or promiscuous protein biotinylation.Proteins · 2024Review
- Detection of Recombinant Proteins SOX2 and OCT4 Interacting in HEK293T Cells Using Real-Time Quantitative PCR.Life (Basel, Switzerland) · 2022Article
- Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation.Biochemistry and biophysics reports · 2022Article
- Specificity and selectivity in post-translational biotin addition.Biochemical Society transactions · 2018Review
- Host biotin is required for liver stage development in malaria parasites.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Modulating the Structure and Function of an Aminoacyl-tRNA Synthetase Cofactor by Biotinylation.The Journal of biological chemistry · 2016Article
- Mechanisms of biotin-regulated gene expression in microbes.Synthetic and systems biotechnology · 2016Review
- A nutritional conditional lethal mutant due to pyridoxine 5'-phosphate oxidase deficiency in Drosophila melanogaster.G3 (Bethesda, Md.) · 2014Article
- Influences of dietary biotin and avidin on growth, survival, deficiency syndrome and hepatic gene expression of juvenile Nile tilapia Oreochromis niloticus.Fish physiology and biochemistry · 2012Article
- Selectivity in post-translational biotin addition to five human carboxylases.The Journal of biological chemistry · 2012Article
- Mutation analysis in 54 propionic acidemia patients.Journal of inherited metabolic disease · 2012Article
- The role of holocarboxylase synthetase in genome stability is mediated partly by epigenomic synergies between methylation and biotinylation events.Epigenetics · 2011Article
- Biotinylation, a post-translational modification controlled by the rate of protein-protein association.The Journal of biological chemistry · 2011Article
- Enhanced in vivo imaging of metabolically biotinylated cell surface reporters.Analytical chemistry · 2011Article
- Biotin regulates the expression of holocarboxylase synthetase in the miR-539 pathway in HEK-293 cells.The Journal of nutrition · 2010Article
- Biotin requirements are lower in human Jurkat lymphoid cells but homeostatic mechanisms are similar to those of HepG2 liver cells.The Journal of nutrition · 2010Article
- The switch regulating transcription of the Escherichia coli biotin operon does not require extensive protein-protein interactions.Chemistry & biology · 2010Article
- Distinct amino termini of two human HCS isoforms influence biotin acceptor substrate recognition.The Journal of biological chemistry · 2009Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Holocarboxylase synthetase (HCS) catalyzes the biotinylation of the four biotin-dependent carboxylases in human cells. Patients with HCS deficiency lack activity of all four carboxylases, indicating that a single HCS is targeted to the mitochondria and cytoplasm. We isolated 21 human HCS cDNA clones, in four size classes of 2.0-4.0 kb, by complementation of an Escherichia coli birA mutant defective in biotin ligase. Expression of the cDNA clones promoted biotinylation of the bacterial biotinyl carboxyl carrier protein as well as a carboxyl-terminal fragment of the alpha subunit of human propionyl-CoA carboxylase expressed from a plasmid. The open reading frame encodes a predicted protein of 726 aa and M(r) 80,759. Northern blot analysis revealed the presence of a 5.8-kb major species and 4.0-, 4.5-, and 8.5-kb minor species of poly(A)+ RNA in human tissues. Human HCS shows specific regions of homology with the BirA protein of E. coli and the presumptive biotin ligase of Paracoccus denitrificans. Several forms of HCS mRNA are generated by alternative splicing, and as a result, two mRNA molecules bear different putative translation initiation sites. A sequence upstream of the first translation initiation site encodes a peptide structurally similar to mitochondrial presequences, but it lacks an in-frame ATG codon to direct its translation. We anticipate that alternative splicing most likely mediates the mitochondrial versus cytoplasmic expression, although the elements required for directing the enzyme to the mitochondria remain to be confirmed.
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