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UniProtKB - Q15126 (PMVK_HUMAN)
Protein
Phosphomevalonate kinase
Gene
PMVK
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the reversible ATP-dependent phosphorylation of mevalonate 5-phosphate to produce mevalonate diphosphate and ADP, a key step in the mevalonic acid mediated biosynthesis of isopentenyl diphosphate and other polyisoprenoid metabolites.
4 PublicationsCaution
Was originally thought to be located in the peroxisome (PubMed:10191291). However, was later shown to be cytosolic (PubMed:14729858, PubMed:27052676).1 Publication2 Publications
Catalytic activityi
- EC:2.7.4.24 Publications
Kineticsi
- KM=25 µM for (R)-5-phosphomevalonate2 Publications
- KM=0.26 mM for ATP2 Publications
- Vmax=46.4 µmol/min/mg enzyme with (R)-5-phosphomevalonate as substrate2 Publications
- Vmax=52 µmol/min/mg enzyme with ATP as substrate2 Publications
: isopentenyl diphosphate biosynthesis via mevalonate pathway Pathwayi
This protein is involved in step 2 of the subpathway that synthesizes isopentenyl diphosphate from (R)-mevalonate.Curated This subpathway is part of the pathway isopentenyl diphosphate biosynthesis via mevalonate pathway, which is itself part of Isoprenoid biosynthesis.View all proteins of this organism that are known to be involved in the subpathway that synthesizes isopentenyl diphosphate from (R)-mevalonate, the pathway isopentenyl diphosphate biosynthesis via mevalonate pathway and in Isoprenoid biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 141 | ATP2 Publications | 1 | |
Binding sitei | 170 | Substrate1 Publication | 1 | |
Binding sitei | 171 | ATP1 Publication | 1 | |
Binding sitei | 176 | ATP1 Publication | 1 | |
Binding sitei | 180 | ATP1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 17 – 23 | ATP2 Publications | 7 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- phosphomevalonate kinase activity Source: UniProtKB
GO - Biological processi
- cholesterol biosynthetic process Source: UniProtKB
- isopentenyl diphosphate biosynthetic process, mevalonate pathway Source: GO_Central
- response to cholesterol Source: UniProtKB
- sterol biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Kinase, Transferase |
Biological process | Cholesterol biosynthesis, Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.4.2, 2681 |
PathwayCommonsi | Q15126 |
Reactomei | R-HSA-191273, Cholesterol biosynthesis R-HSA-2426168, Activation of gene expression by SREBF (SREBP) |
SABIO-RKi | Q15126 |
SignaLinki | Q15126 |
UniPathwayi | UPA00057;UER00099 |
Chemistry databases
SwissLipidsi | SLP:000001241 |
Names & Taxonomyi
Protein namesi | Recommended name: Phosphomevalonate kinase (EC:2.7.4.24 Publications)Short name: PMKase Short name: hPMK |
Gene namesi | Name:PMVK Synonyms:PMKI |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9141, PMVK |
MIMi | 607622, gene |
neXtProti | NX_Q15126 |
VEuPathDBi | HostDB:ENSG00000163344 |
Subcellular locationi
Cytoplasm and Cytosol
- cytosol 2 Publications
Cytosol
- cytosol Source: UniProtKB
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Peroxisome
- peroxisome Source: UniProtKB
Other locations
- membrane Source: UniProtKB
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Involvement in diseasei
Porokeratosis 1, multiple types (POROK1)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of porokeratosis, a disorder of faulty keratinization characterized by one or more atrophic patches surrounded by a distinctive hyperkeratotic ridgelike border called the cornoid lamella. The keratotic lesions can progress to overt cutaneous neoplasms, typically squamous cell carcinomas. Multiple clinical variants of porokeratosis are recognized, including porokeratosis of Mibelli, linear porokeratosis, disseminated superficial actinic porokeratosis, palmoplantar porokeratosis, and punctate porokeratosis. Different clinical presentations can be observed among members of the same family. Individuals expressing more than one variant have also been reported.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_075051 | 69 | K → E in POROK1; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_080138 | 138 – 192 | Missing in POROK1; results in reduced expression and solubility; disturbs subcellular localization with punctate rather than diffuse cytoplasmic distribution. 1 PublicationAdd BLAST | 55 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 17 | K → M: Approximately 8-fold decrease in Vmax for MgATP and R-MVP. Approximately 5-fold increase in KM for MgATP and R-MVP. 1 Publication | 1 | |
Mutagenesisi | 18 | R → Q: Approximately 85-fold decrease in Vmax for MgATP and R-MVP. Approximately 5-fold increase in KM for MgATP and R-MVP. 1 Publication | 1 | |
Mutagenesisi | 19 | K → M: Approximately 9-fold decrease in Vmax for MgATP and R-MVP. Approximately 10-fold increase in KM for MgATP and R-MVP. 1 Publication | 1 | |
Mutagenesisi | 22 | K → M: Approximately 100000-fold decrease in Vmax for MgATP. 1 Publication | 1 | |
Mutagenesisi | 23 | 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. 1 Publication | 1 | |
Mutagenesisi | 48 | K → M: Approximately 1400-fold decrease in Vmax for MgATP and R-MVP. Approximately 3-fold increase in KM for MgATP and R-MVP. 1 Publication | 1 | |
Mutagenesisi | 69 | K → M: Approximately 500-fold decrease in Vmax for MgATP and R-MVP. Approximately 3-fold increase in KM for MgATP and R-MVP. 1 Publication | 1 | |
Mutagenesisi | 73 | 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. 1 Publication | 1 | |
Mutagenesisi | 84 | 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. 1 Publication | 1 | |
Mutagenesisi | 93 | R → M: Almost no change in KM and Vmax for MgATP and R-MVP. | 1 | |
Mutagenesisi | 110 | R → M: Approximately 20000-fold decrease in Vmax for MgATP. 1 Publication | 1 | |
Mutagenesisi | 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. 1 Publication | 1 | |
Mutagenesisi | 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. | 1 | |
Mutagenesisi | 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. | 1 | |
Mutagenesisi | 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. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 10654 |
MalaCardsi | PMVK |
MIMi | 175800, phenotype |
OpenTargetsi | ENSG00000163344 |
Orphaneti | 735, Porokeratosis of Mibelli |
PharmGKBi | PA33465 |
Miscellaneous databases
Pharosi | Q15126, Tchem |
Chemistry databases
GuidetoPHARMACOLOGYi | 641 |
Genetic variation databases
BioMutai | PMVK |
DMDMi | 3024422 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000058472 | 1 – 192 | Phosphomevalonate kinaseAdd BLAST | 192 |
Proteomic databases
EPDi | Q15126 |
jPOSTi | Q15126 |
MassIVEi | Q15126 |
PaxDbi | Q15126 |
PeptideAtlasi | Q15126 |
PRIDEi | Q15126 |
ProteomicsDBi | 60453 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00220648 |
PTM databases
iPTMneti | Q15126 |
PhosphoSitePlusi | Q15126 |
Expressioni
Tissue specificityi
Heart, liver, skeletal muscle, kidney, and pancreas. Lower level in brain, placenta and lung.1 Publication
Inductioni
By sterol.1 Publication
Gene expression databases
Bgeei | ENSG00000163344, Expressed in nucleus accumbens and 240 other tissues |
ExpressionAtlasi | Q15126, baseline and differential |
Genevisiblei | Q15126, HS |
Organism-specific databases
HPAi | ENSG00000163344, Low tissue specificity |
Interactioni
Subunit structurei
Monomer.
1 PublicationBinary interactionsi
Q15126
With | #Exp. | IntAct |
---|---|---|
DDIT4L [Q96D03] | 3 | EBI-1055562,EBI-742054 |
ZNF177 - isoform 2 [Q13360-2] | 3 | EBI-1055562,EBI-12272076 |
Protein-protein interaction databases
BioGRIDi | 115897, 60 interactors |
IntActi | Q15126, 25 interactors |
MINTi | Q15126 |
STRINGi | 9606.ENSP00000357452 |
Miscellaneous databases
RNActi | Q15126, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
AlphaFoldDBi | Q15126 |
SMRi | Q15126 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q15126 |
Family & Domainsi
Phylogenomic databases
eggNOGi | ENOG502QYPQ, Eukaryota |
GeneTreei | ENSGT00390000014801 |
HOGENOMi | CLU_092097_0_0_1 |
InParanoidi | Q15126 |
OMAi | YGFFCRA |
OrthoDBi | 1307762at2759 |
PhylomeDBi | Q15126 |
TreeFami | TF312935 |
Family and domain databases
Gene3Di | 3.40.50.300, 1 hit |
InterProi | View protein in InterPro IPR027417, P-loop_NTPase IPR005919, Pmev_kin_anim |
PANTHERi | PTHR13101, PTHR13101, 1 hit |
Pfami | View protein in Pfam PF04275, P-mevalo_kinase, 1 hit |
PIRSFi | PIRSF036639, PMK_anim, 1 hit |
SUPFAMi | SSF52540, SSF52540, 1 hit |
TIGRFAMsi | TIGR01223, Pmev_kin_anim, 1 hit |
i Sequence
Sequence statusi: Complete.
Q15126-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAPLGGAPRL VLLFSGKRKS GKDFVTEALQ SRLGADVCAV LRLSGPLKEQ
60 70 80 90 100
YAQEHGLNFQ RLLDTSTYKE AFRKDMIRWG EEKRQADPGF FCRKIVEGIS
110 120 130 140 150
QPIWLVSDTR RVSDIQWFRE AYGAVTQTVR VVALEQSRQQ RGWVFTPGVD
160 170 180 190
DAESECGLDN FGDFDWVIEN HGVEQRLEEQ LENLIEFIRS RL
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_075051 | 69 | K → E in POROK1; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_051283 | 125 | V → M1 PublicationCorresponds to variant dbSNP:rs16836525Ensembl. | 1 | |
Natural variantiVAR_080138 | 138 – 192 | Missing in POROK1; results in reduced expression and solubility; disturbs subcellular localization with punctate rather than diffuse cytoplasmic distribution. 1 PublicationAdd BLAST | 55 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS1073.1 |
RefSeqi | NP_006547.1, NM_006556.3 |
Genome annotation databases
Ensembli | ENST00000368467.4; ENSP00000357452.3; ENSG00000163344.6 |
GeneIDi | 10654 |
KEGGi | hsa:10654 |
MANE-Selecti | ENST00000368467.4; ENSP00000357452.3; NM_006556.4; NP_006547.1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS1073.1 |
RefSeqi | NP_006547.1, NM_006556.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3CH4 | X-ray | 1.76 | B | 1-192 | [»] | |
AlphaFoldDBi | Q15126 | |||||
SMRi | Q15126 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 115897, 60 interactors |
IntActi | Q15126, 25 interactors |
MINTi | Q15126 |
STRINGi | 9606.ENSP00000357452 |
Chemistry databases
GuidetoPHARMACOLOGYi | 641 |
SwissLipidsi | SLP:000001241 |
PTM databases
iPTMneti | Q15126 |
PhosphoSitePlusi | Q15126 |
Genetic variation databases
BioMutai | PMVK |
DMDMi | 3024422 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00220648 |
Proteomic databases
EPDi | Q15126 |
jPOSTi | Q15126 |
MassIVEi | Q15126 |
PaxDbi | Q15126 |
PeptideAtlasi | Q15126 |
PRIDEi | Q15126 |
ProteomicsDBi | 60453 |
Protocols and materials databases
Antibodypediai | 34158, 236 antibodies from 28 providers |
DNASUi | 10654 |
Genome annotation databases
Ensembli | ENST00000368467.4; ENSP00000357452.3; ENSG00000163344.6 |
GeneIDi | 10654 |
KEGGi | hsa:10654 |
MANE-Selecti | ENST00000368467.4; ENSP00000357452.3; NM_006556.4; NP_006547.1 |
Organism-specific databases
CTDi | 10654 |
DisGeNETi | 10654 |
GeneCardsi | PMVK |
HGNCi | HGNC:9141, PMVK |
HPAi | ENSG00000163344, Low tissue specificity |
MalaCardsi | PMVK |
MIMi | 175800, phenotype 607622, gene |
neXtProti | NX_Q15126 |
OpenTargetsi | ENSG00000163344 |
Orphaneti | 735, Porokeratosis of Mibelli |
PharmGKBi | PA33465 |
VEuPathDBi | HostDB:ENSG00000163344 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QYPQ, Eukaryota |
GeneTreei | ENSGT00390000014801 |
HOGENOMi | CLU_092097_0_0_1 |
InParanoidi | Q15126 |
OMAi | YGFFCRA |
OrthoDBi | 1307762at2759 |
PhylomeDBi | Q15126 |
TreeFami | TF312935 |
Enzyme and pathway databases
UniPathwayi | UPA00057;UER00099 |
BRENDAi | 2.7.4.2, 2681 |
PathwayCommonsi | Q15126 |
Reactomei | R-HSA-191273, Cholesterol biosynthesis R-HSA-2426168, Activation of gene expression by SREBF (SREBP) |
SABIO-RKi | Q15126 |
SignaLinki | Q15126 |
Miscellaneous databases
BioGRID-ORCSi | 10654, 297 hits in 1085 CRISPR screens |
ChiTaRSi | PMVK, human |
EvolutionaryTracei | Q15126 |
GenomeRNAii | 10654 |
Pharosi | Q15126, Tchem |
PROi | PR:Q15126 |
RNActi | Q15126, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000163344, Expressed in nucleus accumbens and 240 other tissues |
ExpressionAtlasi | Q15126, baseline and differential |
Genevisiblei | Q15126, HS |
Family and domain databases
Gene3Di | 3.40.50.300, 1 hit |
InterProi | View protein in InterPro IPR027417, P-loop_NTPase IPR005919, Pmev_kin_anim |
PANTHERi | PTHR13101, PTHR13101, 1 hit |
Pfami | View protein in Pfam PF04275, P-mevalo_kinase, 1 hit |
PIRSFi | PIRSF036639, PMK_anim, 1 hit |
SUPFAMi | SSF52540, SSF52540, 1 hit |
TIGRFAMsi | TIGR01223, Pmev_kin_anim, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PMVK_HUMAN | |
Accessioni | Q15126Primary (citable) accession number: Q15126 Secondary accession number(s): Q5TZW9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | January 23, 2007 | |
Last modified: | May 25, 2022 | |
This is version 185 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - 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