Mevalonate kinase

Gene ontology
Molecular function	• mevalonate kinase activity • ATP binding • identical protein binding
Cellular component	• peroxisome • cytosol • extracellular exosome
Biological process	• cholesterol biosynthetic process • isoprenoid biosynthetic process • phosphorylation • isopentenyl diphosphate biosynthetic process, mevalonate pathway • small molecule metabolic process • negative regulation of inflammatory response
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 12:
109.57 – 109.6 Mb

Chr 5:
114.44 – 114.46 Mb

PubMed search

Mevalonate kinase is an enzyme that in humans is encoded by the MVK gene.^[2]^[3] Mevalonate kinases are found in a wide variety of organisms from bacteria to mammals. This enzyme catalyzes the following reaction:

ATP + (R)-mevalonate

\rightleftharpoons

ADP + (R)-5-phosphomevalonate

Function

Mevalonate is a key intermediate, and mevalonate kinase a key early enzyme, in isoprenoid and sterol synthesis.^[2]

Mevalonate pathway

Clinical significance

Defects can be associated with hyperimmunoglobulinemia D with recurrent fever.^[4]

Mevalonate kinase deficiency caused by mutation of this gene results in mevalonic aciduria, a disease characterized psychomotor retardation, failure to thrive, hepatosplenomegaly, anemia and recurrent febrile crises. Defects in this gene also cause hyperimmunoglobulinaemia D and periodic fever syndrome, a disorder characterized by recurrent episodes of fever associated with lymphadenopathy, arthralgia, gastrointestinal dismay and skin rash.^[2]

References

↑ PDB: 2X7I; Oke M, Carter LG, Johnson KA, Liu H, McMahon SA, Yan X, Kerou M, Weikart ND, Kadi N, Sheikh MA, Schmelz S, Dorward M, Zawadzki M, Cozens C, Falconer H, Powers H, Overton IM, van Niekerk CA, Peng X, Patel P, Garrett RA, Prangishvili D, Botting CH, Coote PJ, Dryden DT, Barton GJ, Schwarz-Linek U, Challis GL, Taylor GL, White MF, Naismith JH (June 2010). "The Scottish Structural Proteomics Facility: targets, methods and outputs". J. Struct. Funct. Genomics 11 (2): 167–80. doi:10.1007/s10969-010-9090-y. PMC 2883930. PMID 20419351.
1 2 3 "Entrez Gene: mevalonate kinase".
↑ Schafer BL, Bishop RW, Kratunis VJ, Kalinowski SS, Mosley ST, Gibson KM, Tanaka RD (July 1992). "Molecular cloning of human mevalonate kinase and identification of a missense mutation in the genetic disease mevalonic aciduria". J. Biol. Chem. 267 (19): 13229–38. PMID 1377680.
↑ Online 'Mendelian Inheritance in Man' (OMIM) 260920

External links

mevalonate kinase at the US National Library of Medicine Medical Subject Headings (MeSH)

Metabolism: lipid metabolism – ketones/cholesterol synthesis enzymes/steroid metabolism

Mevalonate pathway

To HMG-CoA	Acetyl-Coenzyme A acetyltransferase HMG-CoA synthase (regulated step)

Ketogenesis	HMG-CoA lyase 3-hydroxybutyrate dehydrogenase Thiophorase

To Mevalonic acid	HMG-CoA reductase

To DMAPP	Mevalonate kinase Phosphomevalonate kinase Pyrophosphomevalonate decarboxylase Isopentenyl-diphosphate delta isomerase

Geranyl-	Dimethylallyltranstransferase Geranyl pyrophosphate

To cholesterol

To lanosterol	Farnesyl-diphosphate farnesyltransferase Squalene monooxygenase Lanosterol synthase

7-Dehydrocholesterol path	Lanosterol 14α-demethylase Sterol-C5-desaturase-like 7-Dehydrocholesterol reductase

Desmosterol path	24-dehydrocholesterol reductase

To Bile acids

Steroidogenesis

To pregnenolone

Side-chain cleavage

To corticosteroids

aldosterone: 18-hydroxylase

To sex hormones

To androgens	17α-hydroxylase/17,20 lyase 3β dehydrogenase 17β dehydrogenase 5α reductase 1 2

To estrogens	Aromatase

Other/ungrouped

Transferases: phosphorus-containing groups (EC 2.7)

2.7.1-2.7.4:
phosphotransferase/kinase
(PO₄)

2.7.1: OH acceptor	Hexo- Gluco- Fructo- Hepatic Galacto- Phosphofructo- 1 Liver Muscle Platelet 2 Riboflavin Shikimate Thymidine ADP-thymidine NAD⁺ Glycerol Pantothenate Mevalonate Pyruvate Deoxycytidine PFP Diacylglycerol Phosphoinositide 3 Class I PI 3 Class II PI 3 Sphingosine Glucose-1,6-bisphosphate synthase

2.7.2: COOH acceptor	Phosphoglycerate Aspartate kinase

2.7.3: N acceptor	Creatine

2.7.4: PO₄ acceptor	Phosphomevalonate Adenylate Nucleoside-diphosphate Uridylate Guanylate Thiamine-diphosphate

2.7.6: diphosphotransferase
(P₂O₇)

2.7.7: nucleotidyltransferase
(PO₄-nucleoside)

Polymerase

DNA polymerase	DNA-directed DNA polymerase I II III IV V RNA-directed DNA polymerase Reverse transcriptase Telomerase DNA nucleotidylexotransferase/Terminal deoxynucleotidyl transferase

RNA nucleotidyltransferase	RNA polymerase/DNA-directed RNA polymerase RNA polymerase I RNA polymerase II RNA polymerase III RNA polymerase IV Primase RNA-dependent RNA polymerase PNPase

Phosphorolytic
3' to 5' exoribonuclease

Nucleotidyltransferase

Guanylyltransferase

mRNA capping enzyme

Other

2.7.8: miscellaneous

Phosphatidyltransferases	CDP-diacylglycerol—glycerol-3-phosphate 3-phosphatidyltransferase CDP-diacylglycerol—serine O-phosphatidyltransferase CDP-diacylglycerol—inositol 3-phosphatidyltransferase CDP-diacylglycerol—choline O-phosphatidyltransferase

Glycosyl-1-phosphotransferase	N-acetylglucosamine-1-phosphate transferase

2.7.10-2.7.13: protein kinase
(PO₄; protein acceptor)

2.7.10: protein-tyrosine	see tyrosine kinases

2.7.11: protein-serine/threonine	see serine/threonine-specific protein kinases

2.7.12: protein-dual-specificity	see serine/threonine-specific protein kinases

2.7.13: protein-histidine	Protein-histidine pros-kinase Protein-histidine tele-kinase Histidine kinase

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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Mevalonate kinase

Function

Clinical significance

See also

References

Further reading

External links