Phosphomevalonate kinase - Homo sapiens (Human)

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Q15126 (PMVK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 115. History...

Clusters with 100%, 90%, 50% identity |

Documents (6) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

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) [Reference proteome]

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: K_M=25 µM for (R)-5-phosphomevalonate Ref.5 Ref.6 K_M=0.26 mM for ATP V_max=46.4 µmol/min/mg enzyme with (R)-5-phosphomevalonate as substrate V_max=52 µmol/min/mg enzyme with ATP as substrate

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Cholesterol metabolism Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism
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 Inferred from direct assay Ref.1. Source: UniProtKB isopentenyl diphosphate biosynthetic process, mevalonate pathway Inferred from electronic annotation. Source: UniProtKB-UniPathway response to cholesterol Inferred from expression pattern Ref.4. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay PubMed 14729858. Source: UniProtKB peroxisome Inferred from direct assay Ref.4 PubMed 17180682. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay Ref.6. Source: UniProtKB phosphomevalonate kinase activity Inferred from direct assay PubMed 14680974 Ref.6 Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed By similarity

Chain

2 – 192

191

Phosphomevalonate kinase

PRO_0000058472

Regions

Nucleotide binding

17 – 23

ATP Probable

Motif

190 – 192

Microbody targeting signal Potential

Sites

Binding site

141

ATP Probable

Binding site

170

Substrate

Binding site

171

ATP Probable

Binding site

176

ATP Probable

Binding site

180

ATP Probable

Natural variations

Natural variant

125

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

VAR_051283

Experimental info

Mutagenesis

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

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

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

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

Mutagenesis

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

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

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

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

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

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

Mutagenesis

110

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

Mutagenesis

111

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

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

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

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

192

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

Q15126 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: D7E720D0DDCCA249
Show »

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

« Hide

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q15126. 1 interaction.

MINT

MINT-7034566.

STRING

9606.ENSP00000357452.

PTM databases

PhosphoSite

Q15126.

Polymorphism databases

DMDM

3024422.

2D gel databases

REPRODUCTION-2DPAGE

IPI00220648.

Proteomic databases

PaxDb

Q15126.

PeptideAtlas

Q15126.

PRIDE

Q15126.

Protocols and materials databases

DNASU

10654.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368467; ENSP00000357452; ENSG00000163344.

GeneID

10654.

KEGG

hsa:10654.

UCSC

uc001ffq.3. human.

Organism-specific databases

CTD

10654.

GeneCards

GC01M154897.

HGNC

HGNC:9141. PMVK.

HPA

HPA029900.

MIM

607622. gene.

neXtProt

NX_Q15126.

PharmGKB

PA33465.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG71763.

HOGENOM

HOG000261666.

HOVERGEN

HBG003277.

InParanoid

Q15126.

K13273.

OMA

QPVWLVS.

OrthoDB

EOG466VMX.

PhylomeDB

Q15126.

Enzyme and pathway databases

BioCyc

MetaCyc:HS08830-MONOMER.

BRENDA

2.7.4.2. 2681.

Reactome

REACT_111217. Metabolism.

SABIO-RK

Q15126.

UniPathway

UPA00057; UER00099.

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]

PANTHER

PTHR13101. PTHR13101. 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

ChiTaRS

PMVK. human.

EvolutionaryTrace

Q15126.

GenomeRNAi

10654.

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:	May 1, 2013
This is version 115 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.

Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

2D gel databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents