Reactome | POMGNT2 transfers GlcNAc to Man-DAG1

POMGNT2 transfers GlcNAc to Man-DAG1

Stable Identifier

R-HSA-8879117

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum lumen, endoplasmic reticulum membrane

Synonyms

DAG1 extension by B3GALNT2, POMGNT2, SGK196

ReviewStatus

5/5

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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