Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q15126 (PMVK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phosphomevalonate kinase

Short name=PMKase
Short name=hPMK
EC=2.7.4.2
Gene names
Name:PMVK
Synonyms:PMKI
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length192 AA.
Sequence statusComplete.
Protein existenceEvidence 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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 192192Phosphomevalonate kinase
PRO_0000058472

Regions

Nucleotide binding17 – 237ATP Probable
Motif190 – 1923Microbody targeting signal Potential

Sites

Binding site1411ATP Probable
Binding site1701Substrate
Binding site1711ATP Probable
Binding site1761ATP Probable
Binding site1801ATP Probable

Natural variations

Natural variant1251V → M. Ref.2
Corresponds to variant rs16836525 [ dbSNP | Ensembl ].
VAR_051283

Experimental info

Mutagenesis171K → 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
Mutagenesis181R → 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
Mutagenesis191K → 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
Mutagenesis221K → M: Approximately 100000-fold decrease in Vmax for MgATP. Ref.6
Mutagenesis231D → 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
Mutagenesis481K → 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
Mutagenesis691K → 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
Mutagenesis731R → 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
Mutagenesis841R → 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
Mutagenesis931R → M: Almost no change in Km and Vmax for MgATP and R-MVP.
Mutagenesis1101R → M: Approximately 20000-fold decrease in Vmax for MgATP. Ref.7
Mutagenesis1111R → 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
Mutagenesis1301R → M: Approximately 4-fold decrease in Vmax for MgATP and R-MVP. Approximately 3-fold increase in Km for MgATP and R-MVP.
Mutagenesis1381R → 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.
Mutagenesis1411R → 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 LengthMass (Da)Tools
Q15126 [UniParc].

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

FASTA19221,995
        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' 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]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"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.
CCDSCCDS1073.1.
RefSeqNP_006547.1. NM_006556.3.
UniGeneHs.30954.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3CH4X-ray1.76B1-192[»]
ProteinModelPortalQ15126.
SMRQ15126. Positions 1-192.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115897. 10 interactions.
IntActQ15126. 2 interactions.
MINTMINT-7034566.
STRING9606.ENSP00000357452.

Chemistry

GuidetoPHARMACOLOGY641.

PTM databases

PhosphoSiteQ15126.

Polymorphism databases

DMDM3024422.

2D gel databases

REPRODUCTION-2DPAGEIPI00220648.

Proteomic databases

MaxQBQ15126.
PaxDbQ15126.
PeptideAtlasQ15126.
PRIDEQ15126.

Protocols and materials databases

DNASU10654.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368467; ENSP00000357452; ENSG00000163344.
GeneID10654.
KEGGhsa:10654.
UCSCuc001ffq.3. human.

Organism-specific databases

CTD10654.
GeneCardsGC01M154897.
HGNCHGNC:9141. PMVK.
HPAHPA029900.
MIM607622. gene.
neXtProtNX_Q15126.
PharmGKBPA33465.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG71763.
HOGENOMHOG000261666.
HOVERGENHBG003277.
InParanoidQ15126.
KOK13273.
OMARISEPIK.
OrthoDBEOG7Z95NC.
PhylomeDBQ15126.
TreeFamTF312935.

Enzyme and pathway databases

BioCycMetaCyc:HS08830-MONOMER.
BRENDA2.7.4.2. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ15126.
UniPathwayUPA00057; UER00099.

Gene expression databases

ArrayExpressQ15126.
BgeeQ15126.
CleanExHS_PMVK.
GenevestigatorQ15126.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR027417. P-loop_NTPase.
IPR005919. Pmev_kin_anim.
[Graphical view]
PANTHERPTHR13101. PTHR13101. 1 hit.
PfamPF04275. P-mevalo_kinase. 1 hit.
[Graphical view]
PIRSFPIRSF036639. PMK_anim. 1 hit.
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR01223. Pmev_kin_anim. 1 hit.
ProtoNetSearch...

Other

ChiTaRSPMVK. human.
EvolutionaryTraceQ15126.
GenomeRNAi10654.
NextBio40503.
PROQ15126.
SOURCESearch...

Entry information

Entry namePMVK_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 126 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

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