Biotin–protein ligase

HLCS
Identifiers
AliasesHLCS, HCS, holocarboxylase synthetase, Biotin–protein ligase, Biotin apo-protein ligase
External IDsOMIM: 609018; MGI: 894646; GeneCards: HLCS
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

3141

110948

Ensembl

ENSG00000159267

ENSMUSG00000040820

UniProt

P50747

Q920N2

RefSeq (mRNA)

NM_139145
NM_001360045

RefSeq (protein)

NP_631884
NP_001346974

Location (UCSC)Chr 21: 36.75 – 36.99 MbChr 16: 93.93 – 94.11 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse
Biotin—[propionyl-CoA-carboxylase (ATP-hydrolyzing)] ligase
Identifiers
EC no.6.3.4.10
CAS no.37318-67-5
Databases
BRENDAenzyme data
ExPASyNiceZyme view
KEGGenzyme entry
MetaCycmetabolic pathway
Rheareactions
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

Biotin–protein ligase, also called holocarboxylase synthetase, is a multi-functional enzyme that in humans is encoded by the gene HLCS. This enzyme functions to biotinylate (attach a biotin) to 4 different enzymes that the require it as a cofactor: acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase.

Biotin (B7) is a B vitamin found in foods such as liver, egg yolks, and milk. It's required as a cofactor for the above mentioned carboxylases which are involved in many critical cellular functions, including the production and breakdown of proteins, fats, and carbohydrates.

Function

HLCS biotinates four separate proteins (which themselves are enzymes), and each of these reactions has a different associated enzyme class. As part of the biotin–protein ligase enzyme class (EC 6.3.4.15), HLCS catalyses the following chemical reaction:

biotin + L-lysyl-[protein] + ATP N(6)-biotinyl-L-lysyl-[protein] + AMP + diphosphate + H+

If it is acting on a methylmalonyl-CoA carboxytransferase enzyme, it is called a biotin-transcarboxylase synthetase (EC 6.3.4.9):

ATP + biotin + apo-methylmalonyl-CoA-carboxyltransferase AMP + diphosphate + methylmalonyl-CoA-carboxyltransferase

If it's acting on a propionyl-CoA carboxylase enzyme, it's called a holocarboxylase synthetase (EC 6.3.4.10):

ATP + biotin + apo-propionyl-CoA carboxylase AMP + diphosphate + propionyl-CoA carboxylase

And finally if it is acting on methylcrotonoyl-CoA carboxylase, it is called a biotin–[methylcrotonoyl-CoA-carboxylase] ligase (EC 6.3.4.11):

ATP + biotin + apo-methylcrotonoyl-CoA-carboxylase AMP + diphosphate + methylcrotonoyl-CoA-carboxylase

Gene regulation

Holocarboxylase synthetase may also play a role in regulating the activity of genes. In the nucleus, the enzyme likely attaches biotin molecules to histones, which are structural proteins that bind to DNA and give chromosomes their shape. Changing the shape of histones may help determine whether certain genes are turned on or off; however, it is not known how adding biotin affects gene regulation.

Distribution of enzymes

Animal and fungus orthologs of the human enzyme are the only enzymes reported in expasy with biotin-transcarboxylase synthetase (EC 6.3.4.9) or holocarboxylase synthetase (EC 6.3.4.10) activity. A chloroplastic biotin–protein ligase enzyme (encoded by the plant gene HCS1) has been reported in certain plants (Mouse-ear cress) which has (EC 6.3.4.11) and (EC 6.3.4.15) activity. Finally, (EC 6.3.4.15) activity has been reported for certain multifunctional enzymes in bacteria denoted birA and birA/coaX.

Holocarboxylase synthetase deficiency: About 30 mutations in the HLCS gene have been identified in people with holocarboxylase synthetase deficiency. Most of these mutations substitute one amino acid (a building block of proteins) for another amino acid in the holocarboxylase synthetase enzyme. Many of the known mutations occur in a region of the enzyme that binds to biotin. These mutations reduce the enzyme's ability to attach biotin to carboxylases and histones. Without biotin, carboxylases remain inactive and are unable to process proteins, fats, and carbohydrates. A lack of holocarboxylase synthetase activity may also alter the regulation of certain genes that are important for normal development. Researchers believe that these disruptions in important cellular functions lead to breathing problems, skin rashes, and the other characteristic signs and symptoms of holocarboxylase synthetase deficiency.

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000159267 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000040820 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Biotin--protein ligase". UniProt consortium. Retrieved 2026-10-16.
  6. 1 2 3 EC 6.3.4.15
  7. ↑ EC 6.3.4.9
  8. ↑ EC 6.3.4.10
  9. ↑ EC 6.3.4.11

This article incorporates text from the United States National Library of Medicine, which is in the public domain.