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phosphomevalonate kinase

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Target not currently curated in GtoImmuPdb

Target id: 641

Nomenclature: phosphomevalonate kinase

Family: Lanosterol biosynthesis pathway

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 192 1q21.3 PMVK phosphomevalonate kinase 5
Mouse - 192 3 F1 Pmvk phosphomevalonate kinase
Rat - 194 2q34 Pmvk phosphomevalonate kinase
Previous and Unofficial Names Click here for help
ATP:5-phosphomevalonate phosphotransferase | mevalonate-5-phosphate kinase | mevalonic acid phosphate kinase | phosphomevalonic kinase | PMK | HUMPMKI | PMKA
Database Links Click here for help
Alphafold Q15126 (Hs), Q9D1G2 (Mm), Q5RK24 (Rn)
BRENDA 2.7.4.2
Ensembl Gene ENSG00000163344 (Hs), ENSMUSG00000027952 (Mm), ENSRNOG00000020696 (Rn)
Entrez Gene 10654 (Hs), 68603 (Mm), 310645 (Rn)
Human Protein Atlas ENSG00000163344 (Hs)
KEGG Enzyme 2.7.4.2
KEGG Gene hsa:10654 (Hs), mmu:68603 (Mm), rno:310645 (Rn)
OMIM 607622 (Hs)
Pharos Q15126 (Hs)
RefSeq Nucleotide NM_006556 (Hs), NM_026784 (Mm), NM_027348 (Mm), NM_001008352 (Rn)
RefSeq Protein NP_006547 (Hs), NP_081060 (Mm), NP_081624 (Mm), NP_001008353 (Rn)
UniProtKB Q15126 (Hs), Q9D1G2 (Mm), Q5RK24 (Rn)
Wikipedia PMVK (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human phosphomevalonate kinase
PDB Id:  3CH4
Resolution:  1.76Å
Species:  Human
References:  2
Enzyme Reaction Click here for help
EC Number: 2.7.4.2 ATP + (R)-5-phosphomevalonate = ADP + (R)-5-diphosphomevalonate
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
ADP Substrate is endogenous in the given species Hs Km 4.7x10-5 M pKm 4.3 recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Reverse reaction, averaged over six measurements 3-4
ATP Substrate is endogenous in the given species Hs Km 1.07x10-4 M pKm 4.0 recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Forward reaction, figures averaged over 5 measurements 3-4
(R)-5-phosphomevalonate Substrate is endogenous in the given species Hs Km 3.4x10-5 M pKm 4.5 recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Forward reaction, figures averaged over 5 measurements 3-4
(R)-5-phosphomevalonate Substrate is endogenous in the given species Rn Km 3.57x10-5 M pKm 4.4 in vitro assay, enzyme extracted from rat liver pH 7.4, 37ºC Concentration of substrates and reagents: 10mM ATP, 12.5 MgCl2, 150 µM mevalonate 5-phosphate. 7
(R)-5-diphosphomevalonate Substrate is endogenous in the given species Hs Km 4.1x10-5 M pKm 4.4 recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Reverse reaction, averaged over six measurements 3-4
ADP Substrate is endogenous in the given species Hs Vmax 12 µmol/min/mg recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Vmax value is for the reverse reaction, averaged over six measurements 3-4
ATP Substrate is endogenous in the given species Hs Vmax 52 µmol/min/mg recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Vmax value is for the forward reaction, figures averaged over 5 measurements 3-4
(R)-5-phosphomevalonate Substrate is endogenous in the given species Hs Vmax 46.4 µmol/min/mg recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Vmax value is for the forward reaction, averaged over 5 measurements 3-4
(R)-5-phosphomevalonate Substrate is endogenous in the given species Rn Vmax 71 nmol/h/mg in vitro assay, enzyme extracted from rat liver pH 7.4, 37ºC Concentration of substrates and reagents: 10mM ATP, 12.5 MgCl2, 150 µM mevalonate 5-phosphate. 7
(R)-5-diphosphomevalonate Substrate is endogenous in the given species Hs Vmax 11.3 µmol/min/mg recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Vmax value is for the reverse reaction, averaged over six measurements 3-4
Cofactors Click here for help
Cofactor Species Comments Reference
Mg2+ Human 2,4

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
(R)-5-diphosphomevalonate Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Hs Competitive 4.8 pKi 4
⤷ pKi 4.8 (Ki 1.8x10-5 M) [4]
Conditions: ATP concentration constant and saturating, 42-105µM mevalonate 5-phosphate
3-hydroxy-3-methyl-6-phosphohexanoic acid Small molecule or natural product Rn Inhibition 3.8 pKi 6
⤷ pKi 3.8 (Ki 1.45x10-4 M) [6]
Conditions: Concentration of (R)-mevalonate: 50µM. Substrate: inhibitor ratio of 1.45.
cinnamic acid Small molecule or natural product Ligand has a PDB structure Rn Competitive 2.4 pKi 7
⤷ pKi 2.4 (Ki 3.85x10-3 M) [7]
Description: extracted from rat liver, in vitro assay
Conditions: pH 7.4, 37ºC. Concentration of substrates: 150µM mevalonate-5-phosphate, 10mM ATP, 12.5mM MgCl2
isoferulic acid Small molecule or natural product Ligand has a PDB structure Rn Competitive 2.4 pKi 7
⤷ pKi 2.4 (Ki 3.85x10-3 M) [7]
Description: extracted from rat liver, in vitro assay
Conditions: 150µM mevalonate-5-phosphate, 10mM ATP, 12.5mM MgCl2
View species-specific inhibitor tables
Tissue Distribution Click here for help
Heart, liver, skeletal muscle, kidney and pancreas
Expression level:  High
Species:  Human
Technique:  Northern blot
References:  1
Brain, lung placenta
Expression level:  Low
Species:  Human
Technique:  Northern blot
References:  1

References

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1. Chambliss KL, Slaughter CA, Schreiner R, Hoffmann GF, Gibson KM. (1996) Molecular cloning of human phosphomevalonate kinase and identification of a consensus peroxisomal targeting sequence. J Biol Chem, 271 (29): 17330-4. [PMID:8663599]

2. Chang Q, Yan XX, Gu SY, Liu JF, Liang DC. (2008) Crystal structure of human phosphomevalonate kinase at 1.8 A resolution. Proteins, 73 (1): 254-8. [PMID:18618710]

3. Herdendorf TJ, Miziorko HM. (2006) Phosphomevalonate kinase: functional investigation of the recombinant human enzyme. Biochemistry, 45 (10): 3235-42. [PMID:16519518]

4. Herdendorf TJ, Miziorko HM. (2007) Functional evaluation of conserved basic residues in human phosphomevalonate kinase. Biochemistry, 46 (42): 11780-8. [PMID:17902708]

5. Olivier LM, Chambliss KL, Gibson KM, Krisans SK. (1999) Characterization of phosphomevalonate kinase: chromosomal localization, regulation, and subcellular targeting. J Lipid Res, 40 (4): 672-9. [PMID:10191291]

6. Popjak G, Parker TS, Sarin V, Tropp BE, Engel R. (1978) Inhibition of 5-phosphomevalonate kinase by an isosteric analog of 5-phosphomevalonate. J Am Chem Soc, 100 (25): 8014-8016.

7. Shama Bhat C, Ramasarma T. (1979) Inhibition of rat liver mevalonate pyrophosphate decarboxylase and mevalonate phosphate kinase by phenyl and phenolic compounds. Biochem J, 181 (1): 143-51. [PMID:226078]

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