Defective DPM2 does not transfer mannose to DOLP to form DOLPman

Stable Identifier
R-HSA-4719375
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Dolichyl-phosphate mannosyltransferase (DPM), a heterotrimeric protein embedded in the endoplasmic reticulum membrane, mediates the transfer of mannose (from cytosolic GDP-mannose) to dolichyl phosphate (DOLP) to form dolichyl-phosphate-mannose (DOLPman). The first subunit of the heterotrimer (DPM1) appears to be the actual catalyst, and the other two subunits (DPM2 and 3) appear to stabilise it (Maeda et al. 2000). DPM2 is essential for the ER localisation and stable expression of DPM1 and it enhances binding of the substrate dolichyl phosphate (Maeda et al. 1998). Defects in DPM2 can cause congenital disorder of glycosylation 1u (DPM2-CDG, CDG1u; MIM:615042), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins (Barone et al. 2012). CDG type 1 diseases result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. One mutation, a tyr23-cys (Y23C) substitution at a highly conserved residue encoding a transmembrane domain, can result in the clinical features of DPM2-CDG (Barone et al. 2012).

Literature References
PubMed ID Title Journal Year
10835346 Human dolichol-phosphate-mannose synthase consists of three subunits, DPM1, DPM2 and DPM3

Maeda, Y, Tanaka, S, Hino, J, Kangawa, K, Kinoshita, T

EMBO J 2000
9724629 DPM2 regulates biosynthesis of dolichol phosphate-mannose in mammalian cells: correct subcellular localization and stabilization of DPM1, and binding of dolichol phosphate

Maeda, Y, Tomita, S, Watanabe, R, Ohishi, K, Kinoshita, T

EMBO J. 1998
23109149 DPM2-CDG: a muscular dystrophy-dystroglycanopathy syndrome with severe epilepsy

Barone, R, Aiello, C, Race, V, Morava, E, Foulquier, F, Riemersma, M, Passarelli, C, Concolino, D, Carella, M, Santorelli, F, Vleugels, W, Mercuri, E, Garozzo, D, Sturiale, L, Messina, S, Jaeken, J, Fiumara, A, Wevers, RA, Bertini, E, Matthijs, G, Lefeber, DJ

Ann. Neurol. 2012
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
dolichyl-phosphate beta-D-mannosyltransferase activity of DPM1:DPM2 Y23C:DPM3 [endoplasmic reticulum membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
congenital disorder of glycosylation type I 0050570
Authored
Reviewed
Created
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