POMK 6-phosphorylates Mannose in GalNAc-GlcNAc-Man-DAG1

Stable Identifier
R-HSA-8931653
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.

Once the mannosyl residue attached to DAG1 has had GlcNAc and GalNAc added to it by POMGNT2 and B3GALNT2 respectively, protein O-mannose kinase (POMK, SGK196) can phosphorylate position 6 of the mannosyl residue (Yoshida-Moriguchi et al. 2013). Defects in POMK can cause muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A12 (MDDGA12), a congenital muscular dystrophy that disrupts normal muscle development leading to locomotor dysfuction (Di Costanzo et al. 2014).

Literature References
PubMed ID Title Journal Year
24925318 POMK mutations disrupt muscle development leading to a spectrum of neuromuscular presentations

Di Costanzo, S, Balasubramanian, A, Pond, HL, Rozkalne, A, Pantaleoni, C, Saredi, S, Gupta, VA, Sunu, CM, Yu, TW, Kang, PB, Salih, MA, Mora, M, Gussoni, E, Walsh, CA, Manzini, MC

Hum. Mol. Genet. 2014
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
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
carbohydrate kinase activity of POMK [endoplasmic reticulum membrane]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created
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