Reactome | B3GALNT2 transfers GalNAc to GlcNAc-Man-DAG1

B3GALNT2 transfers GalNAc to GlcNAc-Man-DAG1

Stable Identifier

R-HSA-8931648

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum lumen, endoplasmic reticulum membrane

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B3GALNT2 transfers GalNAc to GlcNAc-Man-DAG1

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Three enzymes are involved in the biosynthesis of a phosphorylated O-mannosyl trisaccharide structure (N-acetylgalactosamine-beta-1,3-N-acetylglucosamine-beta-1,4-(phosphate-6-)mannose) present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity. Defects in any of these enzymes can lead to congenital muscular dystrophy.

The second step is catalysed by UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2 (B3GALNT2), an ER membrane-associated enzyme that transfers N-acetylgalactosamine (GalNAc) to GlcNAc-Man-DAG1 via a 1-3 glycosidic bond (Hiruma et al. 2004, Yoshida-Moriguchi et al. 2013). Defects in B3GALNT2 can cause muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A11 (MDDGA11), a hypoglycosylation defect resulting in a reduced ability of DAG1 to bind laminin and other extracellular matrix ligands. The disorder is characterised by dystroglycanopathy with muscle and brain anomolies (Stevens et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
23929950	SGK196 is a glycosylation-specific O-mannose kinase required for dystroglycan function Yoshida-Moriguchi, T, Willer, T, Anderson, ME, Venzke, D, Whyte, T, Muntoni, F, Lee, H, Nelson, SF, Yu, L, Campbell, KP	Science	2013
14724282	A novel human beta1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAcbeta1-3GlcNAc Hiruma, T, Togayachi, A, Okamura, K, Sato, T, Kikuchi, N, Kwon, YD, Nakamura, A, Fujimura, K, Gotoh, M, Tachibana, K, Ishizuka, Y, Noce, T, Nakanishi, H, Narimatsu, H	J. Biol. Chem.	2004
23453667	Mutations in B3GALNT2 cause congenital muscular dystrophy and hypoglycosylation of α-dystroglycan Stevens, E, Carss, KJ, Cirak, S, Foley, AR, Torelli, S, Willer, T, Tambunan, DE, Yau, S, Brodd, L, Sewry, CA, Feng, L, Haliloglu, G, Orhan, D, Dobyns, WB, Enns, GM, Manning, M, Krause, A, Salih, MA, Walsh, CA, Hurles, M, Campbell, KP, Manzini, MC	Am. J. Hum. Genet.	2013