Reactome | Autoproteolysis of DAG1 to alpha and beta chains

Autoproteolysis of DAG1 to alpha and beta chains

Stable Identifier

R-HSA-9913329

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane, endoplasmic reticulum lumen

ReviewStatus

5/5

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Autoproteolysis of DAG1 to alpha and beta chains

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Dystroglycan is a trans-membrane complex of two subunits, beta–dystroglycan and alpha- dystroglycan, that form the core component of the dystrophin-glycoprotein complex (DGC). While extracellular alpha-dystroglycan binds to alpha-laminin in the extracellular matrix, beta-dystroglycan is the trans-membrane component that binds to alpha-dystroglycan and to the C-terminal domain of dystrophin within DGC (Ibraghimov et al, 1993). The Dystroglycan (DAG1) gene encodes for a single mRNA, translated into a 97 kDa pre-protein which undergoes O- and N-glycosylation, and is autocatalytically cleaved at serine residue 654 to generate alpha- and beta- dystroglycan subunits (Holt et al, 2000; Herzog et al, 2004; Akhavan et al, 2008; reviewed in Bhat et al, 2018). Alpha DAG1(30 653) is heavily O-glycosylated during passage through the secretory system and interactions with laminins in the extracellular matrix are mediated by its glycosyl groups (reviewed in Bhat et al, 2018; Praissman et al, 2014). Beta-DAG1(654 895) spans the plasma membrane and binds and recruits dystrophin, encoded by the DMD gene, which in turn nucleates interactions with numerous cytosolic membrane associated proteins and also binds to the actin cytoskeleton (reviewed in Bhat et al, 2018, Gawor and Prószyński, 2018).

Literature References

PubMed ID	Title	Journal	Year
15175026	Dystroglycan in skin and cutaneous cells: beta-subunit is shed from the cell surface Herzog, C, Has, C, Franzke, CW, Echtermeyer, FG, Schlötzer-Schrehardt, U, Kröger, S, Gustafsson, E, Fässler, R, Bruckner-Tuderman, L	J Invest Dermatol	2004
24786756	Mammalian O-mannosylation pathway: glycan structures, enzymes, and protein substrates Praissman, JL, Wells, L	Biochemistry	2014
28464259	ABC of multifaceted dystrophin glycoprotein complex (DGC) Bhat, HF, Mir, SS, Dar, KB, Bhat, ZF, Shah, RA, Ganai, NA	J Cell Physiol	2018
29068540	The molecular cross talk of the dystrophin-glycoprotein complex Gawor, M, Prószyński, TJ	Ann N Y Acad Sci	2018
10683445	Biosynthesis of dystroglycan: processing of a precursor propeptide Holt, KH, Crosbie, RH, Venzke, DP, Campbell, KP	FEBS Lett	2000
8268918	Human dystroglycan: skeletal muscle cDNA, genomic structure, origin of tissue specific isoforms and chromosomal localization Ibraghimov-Beskrovnaya, O, Milatovich, A, Ozcelik, T, Yang, B, Koepnick, K, Francke, U, Campbell, KP	Hum Mol Genet	1993
17905726	SEA domain proteolysis determines the functional composition of dystroglycan Akhavan, A, Crivelli, SN, Singh, M, Lingappa, VR, Muschler, JL	FASEB J	2008