B3GALNT2 transfers GalNAc to GlcNAc-Man-DAG1

Stable Identifier
R-HSA-8931648
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
acetylgalactosaminyltransferase activity of B3GALNT2 [endoplasmic reticulum membrane]
Physical Entity
Activity
Orthologous Events
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