Defective DOLK does not phosphorylate DCHOL

Stable Identifier
Reaction [transition]
Homo sapiens
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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
17273964 A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy

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

Am J Hum Genet 2007
22242004 Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation

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

PLoS Genet. 2011
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

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

Glycobiology 2002
Catalyst Activity

dolichol kinase activity of DOLK mutants [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of DOLK mutants [endoplasmic reticulum membrane]

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