Reactome | HGSNAT oligomer acetylates Heparan chain(1)

HGSNAT oligomer acetylates Heparan chain(1)

Stable Identifier

R-HSA-2090085

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal membrane, cytosol, lysosomal lumen

ReviewStatus

5/5

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HGSNAT oligomer acetylates Heparan chain(1)

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Heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT) acetylates another non-reducing terminal alpha-glucosamine residue of heparan sulfate. This is a critical reaction for the degradation of heparan sulfate because there is no enzyme that can act on the unacetylated glucosamine molecule. The mechanism by which HGSNAT uses cytosolic acetyl-CoA to transfer the acetyl group to the lysosomal luminal substrate is unknown (Fan et al. 2006). A catalytically inactive 77kDa precursor is transported to the lysosome and is cleaved into a 29kDa N-terminal alpha-chain and a 48kDa C-terminal beta-chain, which are assembled into active 440kDa oligomers in the lysosomal membrane (Durand et al. 2010). Defects in HGSNAT cause mucopolysaccharidosis type IIIC (MPSIIIC, MIM:252930), also called Sanfilippo C syndrome (Fan et al. 2006, Hrebicek et al. 2006).

Literature References

PubMed ID	Title	Journal	Year
16960811	Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C) Fan, X, Zhang, H, Zhang, S, Bagshaw, RD, Tropak, MB, Callahan, JW, Mahuran, DJ	Am J Hum Genet	2006
17033958	Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome) Hrebícek, M, Mrázová, L, Seyrantepe, V, Durand, S, Roslin, NM, Nosková, L, Hartmannová, H, Ivánek, R, Cízkova, A, Poupetová, H, Sikora, J, Urinovská, J, Stranecký, V, Zeman, J, Lepage, P, Roquis, D, Verner, A, Ausseil, J, Beesley, CE, Maire, I, Poorthuis, BJ, van de Kamp, J, van Diggelen, OP, Wevers, RA, Hudson, TJ, Fujiwara, TM, Majewski, J, Morgan, K, Kmoch, S, Pshezhetsky, AV	Am J Hum Genet	2006
20650889	Analysis of the biogenesis of heparan sulfate acetyl-CoA:alpha-glucosaminide N-acetyltransferase provides insights into the mechanism underlying its complete deficiency in mucopolysaccharidosis IIIC Durand, S, Feldhammer, M, Bonneil, E, Thibault, P, Pshezhetsky, AV	J Biol Chem	2010