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

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

Stable Identifier

R-HSA-8931653

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum lumen, endoplasmic reticulum membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

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

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
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
24925318	POMK mutations disrupt muscle development leading to a spectrum of neuromuscular presentations Di Costanzo, S, Yu, TW, Sunu, CM, Pond, HL, Mora, M, Saredi, S, Balasubramanian, A, Kang, PB, Gupta, VA, Gussoni, E, Salih, MA, Manzini, MC, Pantaleoni, C, Walsh, CA, Rozkalne, A	Hum. Mol. Genet.	2014