POMGNT2 transfers GlcNAc to Man-DAG1

Stable Identifier
Reaction [transition]
Homo sapiens
DAG1 extension by B3GALNT2, POMGNT2, SGK196
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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.

In the first step, protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2 (POMGNT2) transfers N-acetyl-D-glucosamine (GlcNAc) to the 4-position of mannosylated DAG1 to generate N-acetyl-D-glucosamine-beta-1,4-O-D-mannosyl-DAG1 (Yoshida-Moriguchi et al. 2013). Defects in POMGNT2 can cause muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A8 (MDDGA8), a congenital muscular dystrophy that severely affects the development of the brain, eyes, and muscle, profound mental retardation, and death usually in the first years of life. This phenotype is also described as Walker-Warburg syndrome (WWS), which represents the most severe end of a phenotypic spectrum of dystroglycanopathies (Manzini et al. 2012).
Literature References
PubMed ID Title Journal Year
23929950 SGK196 is a glycosylation-specific O-mannose kinase required for dystroglycan function

Yoshida-Moriguchi, T, Lee, H, Muntoni, F, Whyte, T, Willer, T, Nelson, SF, Anderson, ME, Yu, L, Campbell, KP, Venzke, D

Science 2013
22958903 Exome sequencing and functional validation in zebrafish identify GTDC2 mutations as a cause of Walker-Warburg syndrome

Tambunan, DE, Mora, M, Eyaid, WM, Gupta, VA, Rodriguez, J, Stevens, CR, Clark, R, Heinzen, EL, Salih, MA, Barry, BJ, Manzini, MC, Gabriel, SB, Moroni, I, Al-Qudah, AK, Walsh, CA, Maynard, TM, Beggs, AH, Shianna, KV, Friedman, JM, Yu, TW, Hill, RS, Partlow, JN

Am. J. Hum. Genet. 2012
Catalyst Activity

acetylglucosaminyltransferase activity of POMGNT2 [endoplasmic reticulum membrane]

Orthologous Events
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