Defective MPDU1 does not promote transfer of Man to (GlcNAc)2 (Man)5 (PP-Dol)1 by ALG3

Stable Identifier
Reaction [transition]
Homo sapiens
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Mannose-P-dolichol utilisation defect 1 protein (MPDU1) is required for the efficient utilisation of the mannose donor dolichyl-phospho-mannose (DOLPman) in the synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols by mannosyltransferases ALG3, ALG9 and ALG12. Defects in MPDU1 can cause congenital disorder of glycosylation 1f (MPDU1-CDG, CDG-1f; MIM:609180), a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterised by under-glycosylated serum glycoproteins of varying sizes. CDG type 1 diseases result in a wide phenotypic spectrum, such as poor neurological development, psychomotor retardation, dysmorphic features, hypotonia, coagulation abnormalities and immunodeficiency. In this condition, DOLPman is no longer utilised in transferase reactions extending LLOs, even as substrate levels and transferase enzyme activities appear normal (Anand et al. 2001, Schenk et al. 2001). Point mutations that can cause MPDU1-CDG are G73E, L119P, M1T, L74S as well as the frameshift mutation L171Sfs*42 (Schenk et al. 2001, Kranz et al. 2001).
Literature References
PubMed ID Title Journal Year
11733556 A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If)

Schmid, T, Ray, S, Denecke, J, Kienz, P, Peter-Katalinic, J, Harms, E, Lehrman, MA, Jackowski-Dohrmann, S, Kranz, C, Freeze, HH, Marquardt, T, Sagi, D, Kreissel, G

J. Clin. Invest. 2001
11733564 MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If

Frank, CG, Revel-Vik, S, Raymond, GV, Hurvitz, H, Imbach, T, Aebi, M, Matthijs, G, Schenk, B, Berger, EG, Raas-Rotschild, A, Grubenmann, CE, Hennet, T, Luder, AS, Korn-Lubetzki, I, Jaeken, J

J. Clin. Invest. 2001
11179430 Requirement of the Lec35 gene for all known classes of monosaccharide-P-dolichol-dependent glycosyltransferase reactions in mammals

Ware, FE, Lehrman, MA, Hofsteenge, J, Doucey, MA, Weik, J, Ray, S, Rush, JS, Waechter, CJ, Anand, M

Mol. Biol. Cell 2001
This event is regulated
Normal reaction
Functional status

Loss of function of MPDU1 mutants [endoplasmic reticulum membrane]

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