HLCS biotinylates 6x(PCCA:PCCB)

Stable Identifier
Reaction [transition]
Homo sapiens
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Biotin (Btn) acts as a coenzyme to 4 carboxylases which exist in their inactive apo forms. These apo-carboxylases are biotinylated to their active halo forms by the activity of biotin-protein ligase (HCLS) (Ingaramo & Beckett 2012, Hiratsuka et al. 1998, Bailey et al. 2010). HCLS is localised to the cytosol and mitochondrion so can perform this activity in either of these locations. Defects in HLCS causes holocarboxylase synthetase deficiency (HLCS deficiency aka biotin-responsive multiple carboxylase deficiency; MIM:253270). HLCS deficiency is an autosomal recessive disorder whereby deficient HLCS activity results in reduced activity of multiple carboxylases. Symptoms include metabolic acidosis, organic aciduria, lethargy, hypotonia, convulsions and dermatitis (Suzuki et al. 2005). Propionyl-CoA carboxylase is most likely functional as a dodecamer, composed of six Btn-containing alpha subunits (PCCA) and six beta subunits (PCCB). The exact order in which this complex is constructed is unknown.

Literature References
PubMed ID Title Journal Year
20153287 Holocarboxylase synthetase: correlation of protein localisation with biological function

Polyak, SW, Bailey, LM, Wallace, JC

Arch. Biochem. Biophys. 2010
9630604 Identification of holocarboxylase synthetase (HCS) proteins in human placenta

Suzuki, Y, Li, X, Narisawa, K, Sakamoto, O, Hiratsuka, M, Aoki, Y

Biochim. Biophys. Acta 1998
22123817 Selectivity in post-translational biotin addition to five human carboxylases

Ingaramo, M, Beckett, D

J. Biol. Chem. 2012
16134170 Mutations in the holocarboxylase synthetase gene HLCS

Suzuki, Y, Aoki, Y, Kure, S, Yang, X, Matsubara, Y

Hum. Mutat. 2005
Catalyst Activity

biotin-protein ligase activity of HLCS [cytosol]

Orthologous Events
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