Defective DOLK does not phosphorylate DCHOL

Stable Identifier
R-HSA-4755600
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Dolichol kinase (DOLK, TMEM15) normally mediates the phosphorylation of a dolichol (DCHOL) residue to form dolichyl phosphate (DOLP) in the ER membrane (Fernandez et al. 2002). DOLP is an important substrate in the synthesis of N- and O-glycosylated proteins and GPI anchors. Defects in DOLK cause congenital disorder of glycosylation type 1m (DOLK-CDG, CDG1m, also known as dolichol kinase deficiency; MIM:610768), a severe multisystem disorder characterised by under-glycosylated serum glycoproteins. This disorder has a very severe phenotype and death can occur in early life (Kranz et al. 2007). Mutations that can cause DOLK-CDG are C99S, Y441S, H408D, W304C and M1I (Kranz et al. 2007, Lefeber et al. 2011).

Literature References
PubMed ID Title Journal Year
22242004 Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation

Lefeber, DJ, de Brouwer, AP, Morava, E, Riemersma, M, Schuurs-Hoeijmakers, JH, Absmanner, B, Verrijp, K, van den Akker, WM, Huijben, K, Steenbergen, G, van Reeuwijk, J, Jozwiak, A, Zucker, N, Lorber, A, Lammens, M, Knopf, C, van Bokhoven, H, Grünewald, S, Lehle, L, Kapusta, L, Mandel, H, Wevers, RA

PLoS Genet. 2011
17273964 A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy

Kranz, C, Jungeblut, C, Denecke, J, Erlekotte, A, Sohlbach, C, Debus, V, Kehl, HG, Harms, E, Reith, A, Reichel, S, Grobe, H, Hammersen, G, Schwarzer, U, Marquardt, T

Am J Hum Genet 2007
12213788 Expression and characterization of a human cDNA that complements the temperature-sensitive defect in dolichol kinase activity in the yeast sec59-1 mutant: the enzymatic phosphorylation of dolichol and diacylglycerol are catalyzed by separate CTP-mediated kinase activities in Saccharomyces cerevisiae

Fernandez, F, Shridas, P, Jiang, S, Aebi, M, Waechter, CJ

Glycobiology 2002
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
dolichol kinase activity of DOLK mutants [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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