Mevalonate kinase

Mammalian protein found in Homo sapiens

Mevalonate Kinase

Crystallographic structure of mevalonate kinase from Staphylococcus aureus.^[1]

Identifiers

EC no.

2.7.1.36

CAS no.

9026-52-2

Databases

IntEnz

IntEnz view

BRENDA

BRENDA entry

ExPASy

NiceZyme view

KEGG

KEGG entry

MetaCyc

metabolic pathway

PRIAM

profile

PDB structures

RCSB PDB PDBe PDBsum

Gene Ontology

AmiGO / QuickGO

Search
PMC	articles
PubMed	articles
NCBI	proteins

MVK

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
2R3V

Identifiers

Aliases

MVK, LRBP, MK, MVLK, POROK3, mevalonate kinase

External IDs

OMIM: 251170, 260920, 610377, 175900; MGI: 107624; HomoloGene: 372; GeneCards: MVK; OMA:MVK - orthologs

Gene location (Human)

Chr.	Chromosome 12 (human)^[2]

Band	12q24.11	Start	109,573,255 bp^[2]
Band	12q24.11	End	109,598,125 bp^[2]

Gene location (Mouse)

Chr.	Chromosome 5 (mouse)^[3]

Band	5 F\|5 55.99 cM	Start	114,582,330 bp^[3]
Band	5 F\|5 55.99 cM	End	114,598,652 bp^[3]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

right lobe of liver

pancreatic ductal cell

skin of abdomen

tibialis anterior muscle

right lobe of thyroid gland

olfactory bulb

left lobe of thyroid gland

kidney

hypothalamus

endothelial cell

Top expressed in

tongue

yolk sac

Meckel's cartilage

neural tube

esophagus

entorhinal cortex

left lobe of liver

lens

More reference expression data

BioGPS

n/a

Gene ontology
Molecular function	transferase activity nucleotide binding kinase activity protein binding mevalonate kinase activity magnesium ion binding ATP binding identical protein binding metal ion binding
Cellular component	cytoplasm cytosol peroxisome
Biological process	steroid metabolic process sterol biosynthetic process phosphorylation lipid metabolism cholesterol metabolic process isoprenoid biosynthetic process cholesterol biosynthetic process negative regulation of inflammatory response steroid biosynthetic process isopentenyl diphosphate biosynthetic process, mevalonate pathway regulation of cholesterol biosynthetic process metabolism
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


4598


17855

Ensembl


ENSG00000110921


ENSMUSG00000041939

UniProt


Q03426


Q9R008

RefSeq (mRNA)


NM_000431 NM_001114185 NM_001301182


NM_023556 NM_001306205

RefSeq (protein)


NP_000422 NP_001107657 NP_001288111


NP_001293134 NP_076045

Location (UCSC)

Chr 12: 109.57 – 109.6 Mb

Chr 5: 114.58 – 114.6 Mb

PubMed search

^[4]

^[5]

Wikidata

View/Edit Human

View/Edit Mouse

Mevalonate kinase is an enzyme (specifically a kinase) that in humans is encoded by the MVK gene.^[6]^[7] Mevalonate kinases are found in a wide variety of organisms from bacteria to mammals. This enzyme catalyzes the following reaction:

{\displaystyle \rightleftharpoons } — 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.^[6] As the second enzyme in the Mevalonate pathway, it catalyzes the phosphorylation of Mevalonic acid to produce Mevalonate-5-phosphate.^[8] A reduction in mevalonate kinase activity to around 5-10% of its typical value is associated with the mevalonate kinase deficiency (MVD) resulting in accumulation of intermediate mevalonic acid.^[9]

Clinical significance

Defects can be associated with hyperimmunoglobulinemia D with recurrent fever.^[10]

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.^[6] The symptoms of the disease typically start at infancy and may be additionally triggered by stress or bacterial infection. Children with mevalonate kinase deficiency may remain undiagnosed for a long time as there is not enough scientific data at the moment to accurately diagnose children with the disease.^[9]

References

^ PDB: 2X7I; Oke M, Carter LG, Johnson KA, Liu H, McMahon SA, Yan X, et al. (June 2010). "The Scottish Structural Proteomics Facility: targets, methods and outputs". Journal of Structural and Functional Genomics. 11 (2): 167–80. doi:10.1007/s10969-010-9090-y. PMC 2883930. PMID 20419351.
^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000110921 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000041939 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c "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". The Journal of Biological Chemistry. 267 (19): 13229–38. doi:10.1016/S0021-9258(18)42199-0. PMID 1377680.
^ Mulders-Manders CM, Simon A (July 2015). "Hyper-IgD syndrome/mevalonate kinase deficiency: what is new?". Seminars in Immunopathology. 37 (4): 371–6. doi:10.1007/s00281-015-0492-6. PMC 4491100. PMID 25990874.
^ ^a ^b Stabile A, Compagnone A, Napodano S, Raffaele CG, Patti M, Rigante D (December 2013). "Mevalonate kinase genotype in children with recurrent fevers and high serum IgD level". Rheumatology International. 33 (12): 3039–42. doi:10.1007/s00296-012-2577-z. PMID 23239036. S2CID 3220012.
^ Online Mendelian Inheritance in Man (OMIM): 260920

External links

mevalonate+kinase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
PDBe-KB provides an overview of all the structure information available in the PDB for Human Mevalonate kinase

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

Cholesterol side-chain cleavage

To corticosteroids

aldosterone: 18-Hydroxylase

cortisol/cortisone: 17α-Hydroxylase
11β-HSD
- 1
- 2

both: 3β-HSD
- 1
- 2
21-Hydroxylase
11β-Hydroxylase

To sex hormones

To androgens	17α-Hydroxylase 17,20-Lyase 3β-HSD 17β-HSD 5α-Reductase 1 2
To estrogens	Aromatase 17β-HSD

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/A γ θ ν T7 Taq II/B α δ ε ζ Pfu III/C IV/X β λ μ TDT V/Y η ι κ RNA-directed DNA polymerase Reverse transcriptase Telomerase
RNA polymerase	Template-directed RNA polymerase I II III IV V ssRNAP POLRMT Primase 1 2 PrimPol RNA-dependent RNA polymerase Polyadenylation PAP 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

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)