Dolichol kinase explained

dolichol kinase
Ec Number:	2.7.1.108
Cas Number:	71768-07-5
Go Code:	0004168

In enzymology, a dolichol kinase is an enzyme that catalyzes the chemical reaction

CTP + dolichol

\rightleftharpoons CDP + dolichyl phosphate

Thus, the two substrates of this enzyme are CTP and dolichol, whereas its two products are CDP and dolichyl phosphate.

This enzyme belongs to the family of transferases, to be specific, those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. The systematic name of this enzyme class is CTP:dolichol O-phosphotransferase. This enzyme is also called dolichol phosphokinase. This enzyme participates in N-glycan biosynthesis.

In humans dolichol kinase is encoded by the DOLK gene.^{[1] [2] [3]}

Function

Dolichyl monophosphate is an essential glycosyl carrier lipid for C- and O-mannosylation and N-glycosylation of proteins and for biosynthesis of glycosylphosphatidylinositol anchors in endoplasmic reticulum (ER). Dolichol kinase catalyzes CTP-mediated phosphorylation of dolichol, the terminal step in de novo dolichyl monophosphate biosynthesis.^[4]

Clinical significance

Mutations in DOLK cause a subtype of the congenital disorders of glycosylation, DOLK-CDG (CDG-Im).^[5]

See also

• Dolichol kinase deficiency

Further reading

• Burton WA, Scher MG, Waechter CJ . 1979 . Enzymatic phosphorylation of dolichol in central nervous tissue . J. Biol. Chem. . 254 . 7129 - 36 . 457672 . 15 . 10.1016/S0021-9258(18)50294-5 . free .
• 10.1139/o80-142 . Rip JW, Carroll KK . 1980 . Properties of a dolichol phosphokinase activity associated with rat liver microsomes . Can. J. Biochem. . 58 . 1051 - 6 . 6257336 . 10 .
• Kranz C, Jungeblut C, Denecke J . A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy. . Am. J. Hum. Genet. . 80 . 3 . 433–40 . 2007 . 17273964 . 10.1086/512130 . 1821118 . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Humphray SJ, Oliver K, Hunt AR . DNA sequence and analysis of human chromosome 9. . Nature . 429 . 6990 . 369–74 . 2004 . 15164053 . 10.1038/nature02465 . 2734081 . 2004Natur.429..369H . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Kikuno R, Nagase T, Ishikawa K . Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. . DNA Res. . 6 . 3 . 197–205 . 1999 . 10470851 . 10.1093/dnares/6.3.197 . etal. free .

External links

• GeneReviews/NCBI/NIH/UW entry on Congenital Disorders of Glycosylation Overview

Notes and References

1. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment . Genome Res . 13 . 10 . 2265–70 . Oct 2003 . 12975309 . 403697 . 10.1101/gr.1293003 .
2. Shridas P, Waechter CJ . Human dolichol kinase, a polytopic endoplasmic reticulum membrane protein with a cytoplasmically oriented CTP-binding site . J Biol Chem . 281 . 42 . 31696–704 . Oct 2006 . 16923818 . 10.1074/jbc.M604087200 . free.
3. Web site: Entrez Gene: DOLK dolichol kinase.
4. Fernandez F, Shridas P, Jiang S, Aebi M, Waechter CJ . 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 . Glycobiology . 12 . 9 . 555–62 . September 2002 . 12213788 . 10.1093/glycob/cwf068. Submitted manuscript .
5. 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 . A defect in dolichol phosphate biosynthesis causes a new inherited disorder with death in early infancy . Am. J. Hum. Genet. . 80 . 3 . 433–40 . March 2007 . 17273964 . 1821118 . 10.1086/512130 .