Q15126 (PMVK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphomevalonate kinase
Short name=PMKase
Short name=hPMK
EC=2.7.4.2

Gene names

Name:	PMVK
Synonyms:	PMKI

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	192 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	ATP + (R)-5-phosphomevalonate = ADP + (R)-5-diphosphomevalonate. Ref.1
Pathway	Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: step 2/3.
Subunit structure	Monomer By similarity.
Subcellular location	Peroxisome Ref.4.
Tissue specificity	Heart, liver, skeletal muscle, kidney, and pancreas. Lower level in brain, placenta and lung. Ref.1
Induction	By sterol. Ref.4
Biophysicochemical properties	Kinetic parameters: KM=25 µM for (R)-5-phosphomevalonate Ref.5 Ref.6 KM=0.26 mM for ATP Vmax=46.4 µmol/min/mg enzyme with (R)-5-phosphomevalonate as substrate Vmax=52 µmol/min/mg enzyme with ATP as substrate

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Peroxisome
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Traceable author statement. Source: Reactome protein phosphorylation Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: Reactome peroxisome Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW phosphomevalonate kinase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 192

191

Phosphomevalonate kinase

PRO_0000058472

Regions

Nucleotide binding

17 – 23

7

ATP Probable

Motif

190 – 192

3

Microbody targeting signal Potential

Sites

Binding site

141

1

ATP Probable

Binding site

170

1

Substrate

Binding site

171

1

ATP Probable

Binding site

176

1

ATP Probable

Binding site

180

1

ATP Probable

Natural variations

Natural variant

125

1

V → M. Ref.2
Corresponds to variant rs16836525 [ dbSNP | Ensembl ].

VAR_051283

Experimental info

Mutagenesis

17

1

K → M: Approximately 8-fold decrease in Vmax for MgATP and R-MVP. Approximately 5-fold increase in Km for MgATP and R-MVP. Ref.6

Mutagenesis

18

1

R → Q: Approximately 85-fold decrease in Vmax for MgATP and R-MVP. Approximately 5-fold increase in Km for MgATP and R-MVP. Ref.6

Mutagenesis

19

1

K → M: Approximately 9-fold decrease in Vmax for MgATP and R-MVP. Approximately 10-fold increase in Km for MgATP and R-MVP. Ref.6

Mutagenesis

22

1

K → M: Approximately 100000-fold decrease in Vmax for MgATP. Ref.6

Mutagenesis

23

1

D → N: Approximately 7-fold decrease in Vmax for MgATP and R-MVP. Approximately 10-fold increase in Km for MgATP and 5-fold increase in Km for R-MVP. Ref.6

Mutagenesis

48

1

K → M: Approximately 1400-fold decrease in Vmax for MgATP and R-MVP. Approximately 3-fold increase in Km for MgATP and R-MVP. Ref.7

Mutagenesis

69

1

K → M: Approximately 500-fold decrease in Vmax for MgATP and R-MVP. Approximately 3-fold increase in Km for MgATP and R-MVP. Ref.7

Mutagenesis

73

1

R → M: Approximately 3000-fold decrease in Vmax for MgATP and R-MVP. No change in Km for MgATP and approximately 3-fold increase in Km for R-MVP. Ref.7

Mutagenesis

84

1

R → M: Approximately 10-fold decrease in Vmax for MgATP and R-MVP. Approximately 3-fold increase in Km for MgATP and 50-fold increase in Km for R-MVP. Ref.7

Mutagenesis

93

1

R → M: Almost no change in Km and Vmax for MgATP and R-MVP.

Mutagenesis

110

1

R → M: Approximately 20000-fold decrease in Vmax for MgATP. Ref.7

Mutagenesis

111

1

R → M: Approximately 65-fold decrease in Vmax for MgATP and R-MVP. Approximately 8-fold increase in Km for MgATP and 60-fold increase in Km for R-MVP. Ref.7

Mutagenesis

130

1

R → M: Approximately 4-fold decrease in Vmax for MgATP and R-MVP. Approximately 3-fold increase in Km for MgATP and R-MVP.

Mutagenesis

138

1

R → M: Approximately 3-fold decrease in Vmax for MgATP and R-MVP. Approximately 5-fold increase in Km for MgATP and no change in Km for R-MVP.

Mutagenesis

141

1

R → M: Approximately 15-fold decrease in Vmax for MgATP and R-MVP. Approximately 50-fold increase in Km for MgATP and approximately 7-fold in Km for R-MVP. Ref.7

Secondary structure

1

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192

Helix Strand Turn

Details...

Beta strand

9 – 15

7

Helix

23 – 32

10

Beta strand

37 – 41

5

Helix

47 – 53

7

Helix

72 – 78

7

Helix

82 – 86

5

Helix

92 – 95

4

Beta strand

102 – 106

5

Helix

112 – 121

10

Beta strand

126 – 133

8

Helix

135 – 140

6

Turn

153 – 155

3

Beta strand

165 – 170

6

Helix

174 – 189

16

Sequences

	Sequence		Length	Mass (Da)
	Q15126 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: D7E720D0DDCCA249	FASTA	192	21,995
	10 20 30 40 50 60 MAPLGGAPRL VLLFSGKRKS GKDFVTEALQ SRLGADVCAV LRLSGPLKEQ YAQEHGLNFQ 70 80 90 100 110 120 RLLDTSTYKE AFRKDMIRWG EEKRQADPGF FCRKIVEGIS QPIWLVSDTR RVSDIQWFRE 130 140 150 160 170 180 AYGAVTQTVR VVALEQSRQQ RGWVFTPGVD DAESECGLDN FGDFDWVIEN HGVEQRLEEQ 190 LENLIEFIRS RL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of human phosphomevalonate kinase and identification of a consensus peroxisomal targeting sequence." Chambliss K.L., Slaughter C.A., Schreiner R., Hoffmann G.F., Gibson K.M. J. Biol. Chem. 271:17330-17334(1996) [PubMed: 8663599] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, TISSUE SPECIFICITY. Tissue: Liver.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-125.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin and Uterus.
[4]	"Characterization of phosphomevalonate kinase: chromosomal localization, regulation, and subcellular targeting." Olivier L.M., Chambliss K.L., Gibson K.M., Krisans S.K. J. Lipid Res. 40:672-679(1999) [PubMed: 10191291] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 33-192, INDUCTION, SUBCELLULAR LOCATION.
[5]	"Post-translational regulation of mevalonate kinase by intermediates of the cholesterol and nonsterol isoprene biosynthetic pathways." Hinson D.D., Chambliss K.L., Toth M.J., Tanaka R.D., Gibson K.M. J. Lipid Res. 38:2216-2223(1997) [PubMed: 9392419] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[6]	"Phosphomevalonate kinase: functional investigation of the recombinant human enzyme." Herdendorf T.J., Miziorko H.M. Biochemistry 45:3235-3242(2006) [PubMed: 16519518] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-17; ARG-18; LYS-19; LYS-22 AND ASP-23, BIOPHYSICOCHEMICAL PROPERTIES.
[7]	"Functional evaluation of conserved basic residues in human phosphomevalonate kinase." Herdendorf T.J., Miziorko H.M. Biochemistry 46:11780-11788(2007) [PubMed: 17902708] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-48; LYS-69; ARG-73; ARG-84; ARG-110; ARG-111 AND ARG-141.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Crystal structure of human phosphomevalonate kinase at 1.8 A resolution." Chang Q., Yan X.-X., Gu S.-Y., Liu J.-F., Liang D.-C. Proteins 73:254-258(2008) [PubMed: 18618710] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L77213 mRNA. Translation: AAC37593.1.
BT019976 mRNA. Translation: AAV38779.1.
BC006089 mRNA. Translation: AAH06089.1.
BC007694 mRNA. Translation: AAH07694.1.
AF026069 Genomic DNA. Translation: AAC60791.1.

IPI

IPI00220648.

RefSeq

NP_006547.1. NM_006556.3.

UniGene

Hs.30954.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3CH4	X-ray	1.76	B	1-192	[»]

ProteinModelPortal

Q15126.

SMR

Q15126. Positions 1-192.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-7034566.

STRING

Q15126.

PTM databases

PhosphoSite

Q15126.

Polymorphism databases

DMDM

3024422.

2D gel databases

REPRODUCTION-2DPAGE

IPI00220648.

Proteomic databases

PeptideAtlas

Q15126.

PRIDE

Q15126.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368467; ENSP00000357452; ENSG00000163344.

GeneID

10654.

KEGG

hsa:10654.

UCSC

uc001ffq.1. human.

Organism-specific databases

CTD

10654.

GeneCards

GC01M154897.

H-InvDB

HIX0001026.

HGNC

HGNC:9141. PMVK.

HPA

HPA029900.

MIM

607622. gene.

neXtProt

NX_Q15126.

PharmGKB

PA33465.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16222.

HOGENOM

HBG716709.

HOVERGEN

HBG003277.

InParanoid

Q15126.

OMA

GKRKCGK.

OrthoDB

EOG466VMX.

PhylomeDB

Q15126.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000163344-MONOMER.

BRENDA

2.7.4.2. 2681.

Reactome

REACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

Q15126.

Bgee

Q15126.

CleanEx

HS_PMVK.

Genevestigator

Q15126.

GermOnline

ENSG00000163344. Homo sapiens.

Family and domain databases

InterPro

IPR005919. Pmev_kin_anim.
[Graphical view]

KO

K13273.

PANTHER

PTHR13101. Pmev_kin_anim. 1 hit.

Pfam

PF04275. P-mevalo_kinase. 1 hit.
[Graphical view]

PIRSF

PIRSF036639. PMK_anim. 1 hit.

TIGRFAMs

TIGR01223. Pmev_kin_anim. 1 hit.

ProtoNet

Search...

Other

NextBio

40503.

SOURCE

Search...

Entry information

Entry name

PMVK_HUMAN

Accession

Primary (citable) accession number: Q15126
Secondary accession number(s): Q5TZW9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 101 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.