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Information on EC 2.7.1.36 - mevalonate kinase and Organism(s) Homo sapiens

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EC Tree
IUBMB Comments
CTP, GTP and UTP can also act as donors.
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Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
mevalonate kinase, mvk, mva kinase, tcmvk, temvk, mevalonic kinase, atp:mevalonate 5-phosphotransferase, mevalonic acid kinase, atp mevalonate 5-phosphotransferase, mevalonate phosphokinase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ATP:mevalonate 5-phosphotransferase
-
-
-
-
kinase, mevalonate (phosphorylating)
-
-
-
-
mevalonate 5-phosphotransferase
-
-
-
-
mevalonate phosphokinase
-
-
-
-
mevalonic acid kinase
-
-
-
-
mevalonic kinase
-
-
-
-
MVA kinase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + (R)-mevalonate = ADP + (R)-5-phosphomevalonate
show the reaction diagram
role for residue E193 in interacting with the cation of the MgATP substrate, and for D204 as the catalytic base that facilitates deprotonation of the C5 hydroxyl of mevalonic acid
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:(R)-mevalonate 5-phosphotransferase
CTP, GTP and UTP can also act as donors.
CAS REGISTRY NUMBER
COMMENTARY hide
9026-52-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
additional information
?
-
-
mevalonate kinase is directly involved in regulation of luteinizing hormone receptor expression
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + (R)-mevalonate
ADP + (R)-5-phosphomevalonate
show the reaction diagram
ATP + mevalonate
ADP + phosphomevalonate
show the reaction diagram
additional information
?
-
-
mevalonate kinase is directly involved in regulation of luteinizing hormone receptor expression
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
25-hydroxycholesterol
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expression of mevalonate kinase is regulated by sterol response element-binding protein-1, which is sensitive to the cllular concentration of 25-hydroxycholesterol. Presence of 25-hydroxycholesterol inhibits mevalonate kinase expression and subsequently its binding to luteinizing hormone receptor mRNA
3,3-dimethylallyl diphosphate
-
-
dolichol phosphate
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-
farnesol
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-
farnesyl diphosphate
farnesyl thiodiphosphate
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feedback inhibition, competitive with ATP
geranyl diphosphate
geranylgeranyl diphosphate
-
-
isopentenyl diphosphate
-
-
lovastatin
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inhibition of isoprenoid pathway, resulting in a dose-dependent reduction of amyloid formed compared with mononuclear cells that are exposed only to serum amyloid. The inhibitory effects of lovastatin are reversible by addition of farnesol but not geranylgeraniol. Farnesyl transferase inhibition also inhibits amyloidogenesis
additional information
-
not inhibited by R-mevalonate 5-diphosphate, geraniol and dolichol up to 0.084, 0.226 and 0.68 mM, respectively
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0324 - 0.4591
(R)-mevalonate
0.15
(R,S)-mevalonate
-
pH 7.0, 25°C, recombinant mevalonate kinase
0.024 - 0.167
(R,S)mevalonate
0.025 - 1.56
ATP
0.012 - 2.5
mevalonate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02
3,3-dimethylallyl diphosphate
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pH 7.0, 25°C, recombinant mevalonate kinase
0.083
dolichol phosphate
-
pH 7.0, 25°C, recombinant mevalonate kinase
0.072
farnesol
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pH 7.0, 25°C, recombinant mevalonate kinase
0.000034 - 0.001713
farnesyl diphosphate
0.000029
farnesyl thiodiphosphate
-
pH 7.5, 30°C
0.116
geranyl diphosphate
0.059
geranylgeranyl diphosphate
-
pH 7.0, 25°C, recombinant mevalonate kinase
0.016
isopentenyl diphosphate
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pH 7.0, 25°C, recombinant mevalonate kinase
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
pH 7.0, 30°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
primary skin fibrobasts from healthy donors and patients with Zellweger syndrome
Manually annotated by BRENDA team
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cultured granulosa cell
Manually annotated by BRENDA team
-
cell line PLC/PRF/5
Manually annotated by BRENDA team
-
LPS-stimulated peripheral blood mononuclear cell
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
MVK functions downstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA) in the mevalonate pathway. The mevalonate pathway provides crucial molecules to cells, and may be an important metabolic pathway in human skin. Short-chain isoprenoids farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) are the intermediate products of the mevalonate pathway, these attach to small G proteins covalently, and serve as molecular switches in many biochemical pathways
physiological function
MVK catalyzes the phosphorylation of mevalonic acid into 5-phosphomevalonate, and functions downstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA) in the mevalonate pathway. The mevalonate pathway provides crucial molecules to cells, and may be an important metabolic pathway in human skin. Analysis of the role of MVK in differentiation, apoptosis and prenylation of keratinocytes, and in the expression of keratin 1 and involucrin, protein prenylation and the processing of small G proteins, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
KIME_HUMAN
396
0
42451
Swiss-Prot
other Location (Reliability: 3)
F5H092_HUMAN
200
0
21803
TrEMBL
other Location (Reliability: 3)
F5H8H2_HUMAN
344
0
37172
TrEMBL
other Location (Reliability: 3)
B2RDU6_HUMAN
396
0
42451
TrEMBL
other Location (Reliability: 3)
A0A1B0GWC2_HUMAN
346
0
36713
TrEMBL
other Location (Reliability: 5)
Q59ET9_HUMAN
421
0
44771
TrEMBL
other Location (Reliability: 5)
F5GXC0_HUMAN
170
0
18263
TrEMBL
other Location (Reliability: 3)
B7Z301_HUMAN
344
0
37157
TrEMBL
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
42000
-
2 * 42000, SDS-PAGE
42500
-
x * 42500, recombinant mevalonate kinase, SDS-PAGE
78000
-
gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
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2 * 42000, SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
free enzyme, 2.5 A resolution. Modeling of complex with farnesyl thiophosphate
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A148T
mutation may be responsible for the hyperimmunoglobulinemia phenotype
C152Y
identification of a mevalonate kinase heterozygous missense point mutation in exon 5 (c.455:G[A]), resulting in the substitution of tyrosine for cysteine (p.C152Y) in a predicted functional domain of the MVK enzyme. The patient shows disseminated superficial actinic porokeratosis (DSAP), which is a genodermatosis with autosomal dominant inheritance and near-complete penetrance clinically featuring uniform 3- to 7-mm annular lesions with scaly borders on sun-exposed face and extremities. The hyperkeratotic rim correlates histopathologically with the presence of a cornoid lamella. Phenotype, overview
D204A
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stable, with 40000fold diminution in kcat. Mutant is able to bind a spin-labeled ATP analogue with stoichiometries and equilibrium binding constants comparable to wild-type
D204N
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stable, with 40000fold diminution in kcat. Mutant is able to bind a spin-labeled ATP analogue with stoichiometries and equilibrium binding constants comparable to wild-type
E148Q
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mutation detected in patient with hyperimmunoglobulinemia D and periodic fever syndrome
E193A
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labile
E193Q
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50fold diminution in Vmax and 20fold increase Km values for ATP, 40fold increase in Km for mevalonate
E19A
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destabilization
E19D
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stable, decrease in Vmax to 40% of wild-type
E19Q
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destabilization
E296Q
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stable. Kinetic parameters similar to wild-type
G336S
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homozygous mutation determined in a patient with severe deficiency in mevalonate kinase associated with nephritis. Catalytic activity is less than 1% of wild-type activity
H20A
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insoluble upon expression in Escherichia coli
H20P
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
I196A
modest changes in Km and Ki values
I268T
I56A
4.5fold increase in Km value for ATP
L264F
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
L265P
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
L53A
modest changes in Km and Ki values
N301T
5-20% of wild-type activity
P165L
mutation may be responsible for the hyperimmunoglobulinemia phenotype
Q390P
-
mutation determined in patient with mevalonate kinase deficiency. Gene additionally has a four-base deletion c.475-478 delACTG
R388X
modest changes in Km and Ki values
S145A
-
37% of wild-type activity
S146A
-
0.02% of wild-type activity
S201A
-
200% of wild-type activity
S378P/V377I/R92Q
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naturally occuring mutation in the MVK gene, the mutation leads to reduced enzyme activity, which participates in the development of the hyperimmunoglobulinemia D and periodic fever syndrome, HIDS, an autosomal recessively inherited autoinflammatory disease, R92Q is a low-penetrance mutation, phenotype, overview
T104A
modest changes in Km and Ki values
T104A/I196A
39fold increase in Ki value
T104A/I196A/R388X
11fold increase in Km value for mevalonate
T243A
-
39% of wild-type activity
T243I
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
V310M
markedly decreased mevalonate kinase activity when expressed in Escherichia coli
V377I
mutation may be responsible for the hyperimmunoglobulinemia phenotype
V377I/I268T
-
mutation determined in patients with hyperimmunoglobulinemia D and periodic fever syndrome. Patients developed significant B cell cytopenia with hypogammaglobulinemia. Therapy of prednisone, azathioprine, and intravenous immunoglobulins resulted in reduced incidence and severity of febrile attacks
V377I/R92Q
-
naturally occuring mutation in the MVK gene, the mutation leads to reduced enzyme activity, which participates in the development of the hyperimmunoglobulinemia D and periodic fever syndrome, HIDS, an autosomal recessively inherited autoinflammatory disease, R92Q is a low-penetrance mutation, phenotype, overview
Y149A
8fold increase in Km value for mevalonate
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
approx. 50% and 70% loss of activity after 40 min and 90 min, respectively, H20P/V377I double mutant is only slightly more temperature sensitive
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme
-
recombinant mevalonat kinase-glutathione S-transferase fusion protein, glutathione Sepharose beads
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in HEK293 Flp-In and CV1 Flp-In cells
-
expression in Escherichia coli
expression of wild-type and N301T mutant mevalonate kinase in COS-7 cells
gene MVK, genotyping
gene MVK, location on chromosome 12q24
-
the mevalonate kinase (MVK) gene has 10 coding exons and one non-coding exon at chromosome 12q24, the MVK protein is encoded by two transcripts of MVK. Recombinant expression of the enzyme in HaCat human keratinocytes using viral vectors, quantitative reverse transcription-PCR enzyme expression analysis
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
-
mutations in the mevalonate kinase gene cause the hyperimmunoglobulin D syndrome, HIDS, and are an appropriate marker for the disease
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Graef, E.; Caselmann, W.H.; Hofschneider, P.H.; Koshy, R.
Enzymic properties of overexpressed HBV-mevalonate kinase fusion proteins and mevalonate kinase proteins in the human hepatoma cell line PLC/PRF/5
Virology
208
696-703
1995
Homo sapiens
Manually annotated by BRENDA team
Hinson, D.D.; Chambliss, K.L.; Toth, M.J.; Tanaka, R.D.; Gibson, K.M.
Post-translational regulation of mevalonate kinase by intermediates of the cholesterol and nonsterol isoprene biosynthetic pathways
J. Lipid Res.
38
2216-2223
1997
Homo sapiens
Manually annotated by BRENDA team
Bishop, R.W.; Chambliss, K.L.; Hoffmann, G.F.; Tanaka, R.D.; Gibson, K.M.
Characterization of the mevalonate kinase 5'-untranslated region provides evidence for coordinate regulation of cholesterol biosynthesis
Biochem. Biophys. Res. Commun.
242
518-524
1998
Homo sapiens
Manually annotated by BRENDA team
Schulte, A.E.; Llamas Duran, E.M.; Van der Heijden, R.; Verpoorte, R.
Mevalonate kinase activity in Catharanthus roseus plants and suspension cultured cells
Plant Sci.
150
59-69
2000
Arabidopsis thaliana, Catharanthus roseus, Homo sapiens, Nepeta cataria, Parthenium argentatum, Rattus norvegicus, Saccharomyces cerevisiae, Spinacia oleracea
-
Manually annotated by BRENDA team
Houten, S.M.; Wanders, R.J.; Waterham, H.R.
Biochemical and genetic aspects of mevalonate kinase and its deficiency
Biochim. Biophys. Acta
1529
19-32
2000
Methanocaldococcus jannaschii, Sus scrofa, Rattus norvegicus (P17256), Homo sapiens (Q03426), Homo sapiens
Manually annotated by BRENDA team
Rios, S.E.; Cho, Y.K.; Miziorko, H.M.
Characterization of mevalonate kinase V377I, a mutant implicated in defective isoprenoid biosynthesis and HIDS/periodic fever syndrome
Biochim. Biophys. Acta
1531
165-168
2001
Homo sapiens
Manually annotated by BRENDA team
Cho, Y.K.; Rios, S.E.; Kim, J.J.; Miziorko, H.M.
Investigation of invariant serine/threonine residues in mevalonate kinase. Tests of the functional significance of a proposed substrate binding motif and a site implicated in human inherited disease
J. Biol. Chem.
276
12573-12578
2001
Homo sapiens
Manually annotated by BRENDA team
Houten, S.M.; Frenkel, J.; Rijkers, G.T.; Wanders, R.J.; Kuis, W.; Waterham, H.R.
Temperature dependence of mutant mevalonate kinase activity as a pathogenic factor in hyper-IgD and periodic fever syndrome
Hum. Mol. Genet.
11
3115-3124
2002
Homo sapiens
Manually annotated by BRENDA team
Voynova, N.E.; Rios, S.E.; Miziorko, H.M.
Staphylococcus aureus mevalonate kinase: isolation and characterization of an enzyme of the isoprenoid biosynthetic pathway
J. Bacteriol.
186
61-67
2004
Homo sapiens, Staphylococcus aureus, Rattus norvegicus
Manually annotated by BRENDA team
Hogenboom, S.; Tuyp, J.J.; Espeel, M.; Koster, J.; Wanders, R.J.; Waterham, H.R.
Mevalonate kinase is a cytosolic enzyme in humans
J. Cell Sci.
117
631-639
2004
Homo sapiens
Manually annotated by BRENDA team
Hoffmann, F.; Lohse, P.; Stojanov, S.; Shin, Y.S.; Renner, E.D.; Kery, A.; Zellerer, S.; Belohradsky, B.H.
Identification of a novel mevalonate kinase gene mutation in combination with the common MVK V377I substitution and the low-penetrance TNFRSF1A R92Q mutation
Eur. J. Hum. Genet.
13
510-512
2005
Homo sapiens
Manually annotated by BRENDA team
Kone-Paut, I.; Sanchez, E.; Le Quellec, A.; Manna, R.; Touitou, I.
Autoinflammatory gene mutations in Behcet's disease
Ann. Rheum. Dis.
66
832-834
2007
Homo sapiens
Manually annotated by BRENDA team
Murphy, C.; Murray, A.M.; Meaney, S.; Gafvels, M.
Regulation by SREBP-2 defines a potential link between isoprenoid and adenosylcobalamin metabolism
Biochem. Biophys. Res. Commun.
355
359-364
2007
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Fu, Z.; Voynova, N.E.; Herdendorf, T.J.; Miziorko, H.M.; Kim, J.J.
Biochemical and structural basis for feedback inhibition of mevalonate kinase and isoprenoid metabolism
Biochemistry
47
3715-3724
2008
Rattus norvegicus (P17256), Homo sapiens (Q03426), Homo sapiens
Manually annotated by BRENDA team
Kuijk, L.M.; Beekman, J.M.; Koster, J.; Waterham, H.R.; Frenkel, J.; Coffer, P.J.
HMG-CoA reductase inhibition induces IL-1beta release through Rac1/PI3K/PKB-dependent caspase-1 activation
Blood
112
3563-3573
2008
Homo sapiens
Manually annotated by BRENDA team
Topaloglu, R.; Ayaz, N.A.; Waterham, H.R.; Yuece, A.; Gumruk, F.; Sanal, O.
Hyperimmunoglobulinemia D and periodic fever syndrome; treatment with etanercept and follow-up
Clin. Rheumatol.
27
1317-1320
2008
Homo sapiens
Manually annotated by BRENDA team
Sornsakrin, M.; Wenner, K.; Ganschow, R.
B cell cytopenia in two brothers with hyper-IgD and periodic fever syndrome
Eur. J. Pediatr.
168
825-831
2008
Homo sapiens
Manually annotated by BRENDA team
Breton Martinez, J.R.; Canovas Martinez, A.; Casana Perez, S.; Escriba Alepuz, J.; Gimenez Vazquez, F.
Mevalonic aciduria: report of two cases
J. Inherit. Metab. Dis.
30
829
2007
Homo sapiens
Manually annotated by BRENDA team
van der hilst, J.C.H.; Kluve-Beckerman, B.; Bodar, E.J.; van der Meer, J.W.M.; Drenth, J.P.H.; Simon, A.
Lovastatin inhibits formation of AA amyloid
J. Leukocyte Biol.
83
1295-1299
2008
Homo sapiens
Manually annotated by BRENDA team
Wang, L.; Nair, A.K.; Menon, K.M.
Ribonucleic acid binding protein-mediated regulation of luteinizing hormone receptor expression in granulosa cells: relationship to sterol metabolism
Mol. Endocrinol.
21
2233-2241
2007
Homo sapiens
Manually annotated by BRENDA team
Nevyjel, M.; Pontillo, A.; Calligaris, L.; Tommasini, A.; DOsualdo, A.; Waterham, H.R.; Granzotto, M.; Crovella, S.; Barbi, E.; Ventura, A.
Diagnostics and therapeutic insights in a severe case of mevalonate kinase deficiency
Pediatrics
119
e523-e527
2007
Homo sapiens
Manually annotated by BRENDA team
Ammouri, W.; Cuisset, L.; Rouaghe, S.; Rolland, M.; Delpech, M.; Grateau, G.; Ravet, N.
Diagnostic value of serum immunoglobulinaemia D level in patients with a clinical suspicion of hyper IgD syndrome
Rheumatology
46
1597-1600
2007
Homo sapiens
Manually annotated by BRENDA team
Lequerre, T.; Vittecoq, O.; Pouplin, S.; Klemmer, N.; Mejjad, O.; Daragon, A.; Prieur, A.M.; Le Loet, X.
Mevalonate kinase deficiency syndrome with structural damage responsive to anakinra
Rheumatology
46
1860-1862
2007
Homo sapiens
Manually annotated by BRENDA team
Potter, D.; Miziorko, H.M.
Identification of catalytic residues in human mevalonate kinase
J. Biol. Chem.
272
25449-25454
1997
Homo sapiens
Manually annotated by BRENDA team
Steichen, O.; van der Hilst, J.; Simon, A.; Cuisset, L.; Grateau, G.
A clinical criterion to exclude the hyperimmunoglobulin D syndrome (mild mevalonate kinase deficiency) in patients with recurrent fever
J. Rheumatol.
36
1677-1681
2009
Homo sapiens
Manually annotated by BRENDA team
Li, M.; Min, W.; Wang, J.; Wang, L.; Li, Y.; Zhou, N.; Yang, Z.; Qian, Q.
Effects of mevalonate kinase interference on cell differentiation, apoptosis, prenylation and geranylgeranylation of human keratinocytes are attenuated by farnesyl pyrophosphate or geranylgeranyl pyrophosphate
Exp. Therap. Med.
19
2861-2870
2020
Homo sapiens (Q03426), Homo sapiens
Manually annotated by BRENDA team
Glinos, G.; Pastar, I.; Giubellino, A.; Tomic-Canic, M.; Miteva, M.; Stone, R.
Novel mevalonate kinase missense mutation in a patient with disseminated superficial actinic porokeratosis
JAAD Case Rep.
4
340-343
2018
Homo sapiens (Q03426)
Manually annotated by BRENDA team