Information on EC 2.7.1.108 - dolichol kinase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.1.108
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RECOMMENDED NAME
GeneOntology No.
dolichol kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
CTP + dolichol = CDP + dolichyl phosphate
show the reaction diagram
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
Phosphorylation
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
dolichol and dolichyl phosphate biosynthesis
N-Glycan biosynthesis
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
CTP:dolichol O-phosphotransferase
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CAS REGISTRY NUMBER
COMMENTARY hide
71768-07-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
soybean
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Manually annotated by BRENDA team
Wistar
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Manually annotated by BRENDA team
strain SF402-4D (Ferro-Novick et al., 1984), temperature sensitive mutants, mutants impaired in Sec59p (sec59-1), cells are defective in CTP-dependent dolichol kinase
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Manually annotated by BRENDA team
rye
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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a deficiency of dolichol kinase, catalyzing the final step of dolichol phosphate synthesis is the first defect of the dolichyl phosphate pathway known to cause a severe hypoglycosylation phenotype in humans, length, weight and head circumference are normal at birth but secondary microcephaly, developing in the first month of life is a common finding in all patients; identifikation of 4 patients who are homozygous for one of 2 mutations (C99S and Y441S) in the corresponding hDK1 gene, the residual activity of mutant is 2-4% when compared with control cells, the mutated alleles fail to complement the temperature-sensitive phenotype of dolichol kinase-deficient yeast cells, whereas the wild-type allele restores the normal growth phenotype, affected patients present with a very severe clinical phenotype, with death in early infancy, 2 of the patients died from dilative cardiomyopathy
metabolism
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dolichol metabolim, the enzymatic product dolichyl phosphate is a lipid carrier embedded in the endoplasmic reticulum membrane essential for the synthesis of N-glycans, GPI-anchors and protein C- and O-mannosylation
physiological function
a strain impaired in dolichol kinase function shows aberrant cell wall structure and composition. the strain is resistant to itraconazole, but sensitive to 5-fluorocytosine, amphotericin B, caspofungin. The minimal inhibitory concentration of caspofungin and amphotericin B is 2fold lower for the mutant than for the respective wild-type strain. The sensitivity of the mutant can be brought back to the wild-type level by a multicopy suppressor of the thermosensitive phenotype, the RER2 gene, encoding cis-prenyltransferase involved in dolichol biosynthesis
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
CTP + dolichol
CDP + dolichyl phosphate
show the reaction diagram
CTP + ficaprenol
CDP + ficaprenyl phosphate
show the reaction diagram
CTP + polyprenol
CDP + polyprenyl phosphate
show the reaction diagram
dCTP + dolichol
dCDP + dolichyl phosphate
show the reaction diagram
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-
?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
CTP + dolichol
CDP + dolichyl phosphate
show the reaction diagram
additional information
?
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the chain length of eukaryotic dolichol molecules is species specific and differs from 14-17 isoprene units in unicellular organisms like the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, mammalian cells produce longer dolichol molecules with 18-21 isoprene units
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cd2+
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slight activation
Fe2+
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slight activation
Ni2+
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slight activation
Sr2+
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slight activation
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Ca2+
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above 6 mM
chlorpromazine
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Co2+
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above 6 mM
dCDP
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Mn2+
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above 6 mM
Trifluoperazine
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Triton X-100
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above 0.5% w/v, activation below
Zn2+
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-
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(R)-dolichol (C95)
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markedly stimulated by addition, Km 0.009 mM
(S)-dolichol (C95)
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markedly stimulated by addition, Km 0.009 mM
2-mercaptoethanol
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slight stimulation
dimyristoylphosphatidylcholine
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stimulatory in 1:1 ratio with deoxycholate
dithiothreitol
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slight stimulation of activity
monothioglycerol
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slight stimulation
phosphatidylcholine
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stimulated by after dialysis
phosphatidylethanolamine
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stimulated by after dialysis
Triton X-100
additional information
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sodium dodecylsulfate is ineffective in stimulating enzymic activity
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0065 - 4
CTP
0.0091
dCTP
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pH 7.2, 37C
0.023 - 0.075
dolichol
additional information
additional information
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.121
CDP
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pH 7.2, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.15
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relative specific activity in the soluble fraction
0.21
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relative specific activity in the mitochondrial lysosomal fraction
0.52
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relative specific activity in the nuclear fraction
3.8
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relative specific activity in the microsomal fraction, rough and smooth endoplasmic reticulum are found to have higher specific activities than the Golgi fraction
additional information
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extracts gained from patient fibroblasts show remarkably lower enzyme activity than extracts from control cells, in comparison with controls, the decrease in activity was 94.5-98.6% for all patients
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 8
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second optimum at pH 9.5
7.4 - 7.7
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7.4
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Tris/maleate buffer, second optimum at pH 9.0
7.5
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8
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shoulder at pH 6.5
8.5
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9
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glycine buffer, second optimum at pH 7.4
9.5
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second optimum at pH 7.0-8.0
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 11
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no second optimum with Tris-HCl, activity increases fairly linearly between pH 8.0 and 10.0, activity decreases about 25% between pH 9.5 and 10.0 in Chaps buffer
4 - 10
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about half-maximal activity at pH 6.0 and 8.0
6.6 - 10.2
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broad pH-activity profile with good activity observed from pH 7.0-10.0, about half-maximal activity at pH 6.6 and 10.2
6.6 - 9.6
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2 optima, about half-maximal activity at pH 6.6, pH 8.5 and pH 9.6
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30 - 37
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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polytopic membrane protein localized in the endoplasmic reticulum with an N-terminus extended into the lumen and a cytoplasmically oriented C-terminus
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
59000 - 60000
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SDS-PAGE
59270
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predicted from cDNA open reading frame
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-17C, 65% of original activity retains when stored for 6 weeks
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-17C, stable for at least 1 month
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-20C, stable for at least 15 days
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-20C, stored frozen as pellet for months with little loss of activity
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4C, no detectable loss of activity when solubilized extract is kept for 24 h
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partially
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
human cDNA complements defect in dolichol kinase activity in Saccharomyces cerevisiae sec59-1 mutant, human SEC59 gene also expressed in Sf-9 cells
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overexpression of normal or variant forms of hDK in CHO cells and in yeast sec59-1 cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE