Defective DPM2 does not transfer mannose to DOLP to form DOLPman

Stable Identifier
Reaction [transition]
Homo sapiens
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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
9724629 DPM2 regulates biosynthesis of dolichol phosphate-mannose in mammalian cells: correct subcellular localization and stabilization of DPM1, and binding of dolichol phosphate

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

EMBO J. 1998
10835346 Human dolichol-phosphate-mannose synthase consists of three subunits, DPM1, DPM2 and DPM3

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

EMBO J 2000
23109149 DPM2-CDG: a muscular dystrophy-dystroglycanopathy syndrome with severe epilepsy

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

Ann. Neurol. 2012
Catalyst Activity

dolichyl-phosphate beta-D-mannosyltransferase activity of DPM1:DPM2 Y23C:DPM3 [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of DPM1:DPM2 Y23C:DPM3 [endoplasmic reticulum membrane]

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