UniProtKB - P53602 (MVD1_HUMAN)
Protein
Diphosphomevalonate decarboxylase
Gene
MVD
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the ATP dependent decarboxylation of (R)-5-diphosphomevalonate to form isopentenyl diphosphate (IPP). Functions in the mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP), a key precursor for the biosynthesis of isoprenoids and sterol synthesis.3 Publications
Caution
Was originally thought to be located in the peroxisome (PubMed:11108725). However, was later shown to be cytosolic (PubMed:14972328).2 Publications
Catalytic activityi
- EC:4.1.1.333 Publications
Kineticsi
- KM=7.4 µM for (R)-5-diphosphomevalonate1 Publication
- KM=28.9 µM for (S,R)-5-diphosphomevalonate1 Publication
- KM=0.69 mM for ATP1 Publication
- KM=0.32 mM for ATP1 Publication
: cholesterol biosynthesis Pathwayi
This protein is involved in the pathway cholesterol biosynthesis, which is part of Steroid biosynthesis.CuratedView all proteins of this organism that are known to be involved in the pathway cholesterol biosynthesis and in Steroid biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 78 | (R)-5-diphosphomevalonateBy similarity | 1 | |
Binding sitei | 212 | (R)-5-diphosphomevalonateBy similarity | 1 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- diphosphomevalonate decarboxylase activity Source: UniProtKB
- Hsp70 protein binding Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
GO - Biological processi
- cholesterol biosynthetic process Source: Reactome
- dolichyl diphosphate biosynthetic process Source: Reactome
- isopentenyl diphosphate biosynthetic process, mevalonate pathway Source: GO_Central
- isoprenoid biosynthetic process Source: UniProtKB
- positive regulation of cell population proliferation Source: UniProtKB
- regulation of cholesterol biosynthetic process Source: Reactome
Keywordsi
Molecular function | Lyase |
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
BioCyci | MetaCyc:ENSG00000167508-MONOMER |
BRENDAi | 4.1.1.33, 2681 |
PathwayCommonsi | P53602 |
Reactomei | R-HSA-191273, Cholesterol biosynthesis R-HSA-2426168, Activation of gene expression by SREBF (SREBP) R-HSA-446199, Synthesis of Dolichyl-phosphate |
SABIO-RKi | P53602 |
UniPathwayi | UPA00063 |
Chemistry databases
SwissLipidsi | SLP:000001242 |
Names & Taxonomyi
Protein namesi | Recommended name: Diphosphomevalonate decarboxylase (EC:4.1.1.333 Publications)Alternative name(s): Mevalonate (diphospho)decarboxylase Short name: MDDase Mevalonate pyrophosphate decarboxylase |
Gene namesi | Name:MVD Synonyms:MPD1 Publication |
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
EuPathDBi | HostDB:ENSG00000167508.10 |
HGNCi | HGNC:7529, MVD |
MIMi | 603236, gene |
neXtProti | NX_P53602 |
Subcellular locationi
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Involvement in diseasei
Porokeratosis 7, multiple types (POROK7)2 Publications
The disease is caused by mutations 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_075052 | 101 | P → R in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs200033380Ensembl. | 1 | |
Natural variantiVAR_075053 | 128 | A → V in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs776358937Ensembl. | 1 | |
Natural variantiVAR_075054 | 161 | R → L in POROK7; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_075055 | 161 | R → Q in POROK7; 1000-fold diminution in diphosphomevalonate decarboxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs144010349Ensembl. | 1 | |
Natural variantiVAR_075056 | 228 | R → Q in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs770939767Ensembl. | 1 | |
Natural variantiVAR_075057 | 228 | R → W in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs776684503Ensembl. | 1 | |
Natural variantiVAR_075058 | 249 | F → S in POROK7. 1 PublicationCorresponds to variant dbSNP:rs761991070EnsemblClinVar. | 1 | |
Natural variantiVAR_075059 | 292 | N → S in POROK7. 1 PublicationCorresponds to variant dbSNP:rs755948940EnsemblClinVar. | 1 | |
Natural variantiVAR_075060 | 371 | Missing in POROK7; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_075061 | 376 | G → R in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs546127665Ensembl. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 17 | N → A: 15-fold inflation in KM for mevalonate diphosphate. 1 Publication | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 4597 |
MalaCardsi | MVD |
MIMi | 614714, phenotype |
OpenTargetsi | ENSG00000167508 |
Orphaneti | 79152, Disseminated superficial actinic porokeratosis |
PharmGKBi | PA31330 |
Miscellaneous databases
Pharosi | P53602, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4340 |
GuidetoPHARMACOLOGYi | 642 |
Polymorphism and mutation databases
BioMutai | MVD |
DMDMi | 1706681 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000087012 | 2 – 400 | Diphosphomevalonate decarboxylaseAdd BLAST | 399 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 96 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | P53602 |
jPOSTi | P53602 |
MassIVEi | P53602 |
MaxQBi | P53602 |
PaxDbi | P53602 |
PeptideAtlasi | P53602 |
PRIDEi | P53602 |
ProteomicsDBi | 56588 |
PTM databases
iPTMneti | P53602 |
PhosphoSitePlusi | P53602 |
Expressioni
Tissue specificityi
Expressed in heart, skeletal muscle, lung, liver, brain, pancreas, kidney and placenta.1 Publication
Gene expression databases
Bgeei | ENSG00000167508, Expressed in right adrenal gland cortex and 150 other tissues |
ExpressionAtlasi | P53602, baseline and differential |
Genevisiblei | P53602, HS |
Organism-specific databases
HPAi | ENSG00000167508, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer.
1 PublicationGO - Molecular functioni
- Hsp70 protein binding Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 110682, 40 interactors |
IntActi | P53602, 10 interactors |
STRINGi | 9606.ENSP00000301012 |
Chemistry databases
BindingDBi | P53602 |
Miscellaneous databases
RNActi | P53602, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P53602 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P53602 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 23 – 26 | (R)-5-diphosphomevalonate bindingBy similarity | 4 | |
Regioni | 156 – 161 | (R)-5-diphosphomevalonate bindingBy similarity | 6 |
Sequence similaritiesi
Belongs to the diphosphomevalonate decarboxylase family.Curated
Phylogenomic databases
eggNOGi | KOG2833, Eukaryota |
GeneTreei | ENSGT00390000015359 |
HOGENOMi | CLU_040369_4_4_1 |
InParanoidi | P53602 |
OMAi | LTLHAMM |
OrthoDBi | 1065019at2759 |
PhylomeDBi | P53602 |
TreeFami | TF105952 |
Family and domain databases
Gene3Di | 3.30.230.10, 1 hit 3.30.70.890, 1 hit |
InterProi | View protein in InterPro IPR036554, GHMP_kinase_C_sf IPR006204, GHMP_kinase_N_dom IPR005935, Mev_decarb IPR029765, Mev_diP_decarb IPR041431, Mvd1_C IPR020568, Ribosomal_S5_D2-typ_fold IPR014721, Ribosomal_S5_D2-typ_fold_subgr |
Pfami | View protein in Pfam PF00288, GHMP_kinases_N, 1 hit PF18376, MDD_C, 1 hit |
PIRSFi | PIRSF015950, Mev_P_decrbx, 1 hit |
SUPFAMi | SSF54211, SSF54211, 1 hit SSF55060, SSF55060, 1 hit |
TIGRFAMsi | TIGR01240, mevDPdecarb, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
P53602-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MASEKPLAAV TCTAPVNIAV IKYWGKRDEE LVLPINSSLS VTLHQDQLKT
60 70 80 90 100
TTTAVISKDF TEDRIWLNGR EEDVGQPRLQ ACLREIRCLA RKRRNSRDGD
110 120 130 140 150
PLPSSLSCKV HVASVNNFPT AAGLASSAAG YACLAYTLAR VYGVESDLSE
160 170 180 190 200
VARRGSGSAC RSLYGGFVEW QMGEQADGKD SIARQVAPES HWPELRVLIL
210 220 230 240 250
VVSAEKKLTG STVGMRASVE TSPLLRFRAE SVVPARMAEM ARCIRERDFP
260 270 280 290 300
SFAQLTMKDS NQFHATCLDT FPPISYLNAI SWRIIHLVHR FNAHHGDTKV
310 320 330 340 350
AYTFDAGPNA VIFTLDDTVA EFVAAVWHGF PPGSNGDTFL KGLQVRPAPL
360 370 380 390 400
SAELQAALAM EPTPGGVKYI IVTQVGPGPQ ILDDPCAHLL GPDGLPKPAA
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH3BP35 | H3BP35_HUMAN | Diphosphomevalonate decarboxylase | MVD | 271 | Annotation score: | ||
H3BQ47 | H3BQ47_HUMAN | Diphosphomevalonate decarboxylase | MVD | 91 | Annotation score: | ||
H3BVC4 | H3BVC4_HUMAN | Diphosphomevalonate decarboxylase | MVD | 51 | Annotation score: | ||
H3BRZ1 | H3BRZ1_HUMAN | Diphosphomevalonate decarboxylase | MVD | 41 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_075052 | 101 | P → R in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs200033380Ensembl. | 1 | |
Natural variantiVAR_075053 | 128 | A → V in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs776358937Ensembl. | 1 | |
Natural variantiVAR_075054 | 161 | R → L in POROK7; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_075055 | 161 | R → Q in POROK7; 1000-fold diminution in diphosphomevalonate decarboxylase activity. 2 PublicationsCorresponds to variant dbSNP:rs144010349Ensembl. | 1 | |
Natural variantiVAR_075056 | 228 | R → Q in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs770939767Ensembl. | 1 | |
Natural variantiVAR_075057 | 228 | R → W in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs776684503Ensembl. | 1 | |
Natural variantiVAR_075058 | 249 | F → S in POROK7. 1 PublicationCorresponds to variant dbSNP:rs761991070EnsemblClinVar. | 1 | |
Natural variantiVAR_051605 | 278 | N → H. Corresponds to variant dbSNP:rs34519538Ensembl. | 1 | |
Natural variantiVAR_075059 | 292 | N → S in POROK7. 1 PublicationCorresponds to variant dbSNP:rs755948940EnsemblClinVar. | 1 | |
Natural variantiVAR_075060 | 371 | Missing in POROK7; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_075061 | 376 | G → R in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs546127665Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U49260 mRNA Translation: AAC50440.1 BT006930 mRNA Translation: AAP35576.1 CH471184 Genomic DNA Translation: EAW66792.1 BC000011 mRNA Translation: AAH00011.1 |
CCDSi | CCDS10968.1 |
RefSeqi | NP_002452.1, NM_002461.2 |
Genome annotation databases
Ensembli | ENST00000301012; ENSP00000301012; ENSG00000167508 |
GeneIDi | 4597 |
KEGGi | hsa:4597 |
UCSCi | uc002flg.2, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U49260 mRNA Translation: AAC50440.1 BT006930 mRNA Translation: AAP35576.1 CH471184 Genomic DNA Translation: EAW66792.1 BC000011 mRNA Translation: AAH00011.1 |
CCDSi | CCDS10968.1 |
RefSeqi | NP_002452.1, NM_002461.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3D4J | X-ray | 2.40 | A/B | 1-400 | [»] | |
SMRi | P53602 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110682, 40 interactors |
IntActi | P53602, 10 interactors |
STRINGi | 9606.ENSP00000301012 |
Chemistry databases
BindingDBi | P53602 |
ChEMBLi | CHEMBL4340 |
GuidetoPHARMACOLOGYi | 642 |
SwissLipidsi | SLP:000001242 |
PTM databases
iPTMneti | P53602 |
PhosphoSitePlusi | P53602 |
Polymorphism and mutation databases
BioMutai | MVD |
DMDMi | 1706681 |
Proteomic databases
EPDi | P53602 |
jPOSTi | P53602 |
MassIVEi | P53602 |
MaxQBi | P53602 |
PaxDbi | P53602 |
PeptideAtlasi | P53602 |
PRIDEi | P53602 |
ProteomicsDBi | 56588 |
Protocols and materials databases
Antibodypediai | 30739, 189 antibodies |
DNASUi | 4597 |
Genome annotation databases
Ensembli | ENST00000301012; ENSP00000301012; ENSG00000167508 |
GeneIDi | 4597 |
KEGGi | hsa:4597 |
UCSCi | uc002flg.2, human |
Organism-specific databases
CTDi | 4597 |
DisGeNETi | 4597 |
EuPathDBi | HostDB:ENSG00000167508.10 |
GeneCardsi | MVD |
HGNCi | HGNC:7529, MVD |
HPAi | ENSG00000167508, Low tissue specificity |
MalaCardsi | MVD |
MIMi | 603236, gene 614714, phenotype |
neXtProti | NX_P53602 |
OpenTargetsi | ENSG00000167508 |
Orphaneti | 79152, Disseminated superficial actinic porokeratosis |
PharmGKBi | PA31330 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2833, Eukaryota |
GeneTreei | ENSGT00390000015359 |
HOGENOMi | CLU_040369_4_4_1 |
InParanoidi | P53602 |
OMAi | LTLHAMM |
OrthoDBi | 1065019at2759 |
PhylomeDBi | P53602 |
TreeFami | TF105952 |
Enzyme and pathway databases
UniPathwayi | UPA00063 |
BioCyci | MetaCyc:ENSG00000167508-MONOMER |
BRENDAi | 4.1.1.33, 2681 |
PathwayCommonsi | P53602 |
Reactomei | R-HSA-191273, Cholesterol biosynthesis R-HSA-2426168, Activation of gene expression by SREBF (SREBP) R-HSA-446199, Synthesis of Dolichyl-phosphate |
SABIO-RKi | P53602 |
Miscellaneous databases
BioGRID-ORCSi | 4597, 448 hits in 845 CRISPR screens |
ChiTaRSi | MVD, human |
EvolutionaryTracei | P53602 |
GenomeRNAii | 4597 |
Pharosi | P53602, Tchem |
PROi | PR:P53602 |
RNActi | P53602, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000167508, Expressed in right adrenal gland cortex and 150 other tissues |
ExpressionAtlasi | P53602, baseline and differential |
Genevisiblei | P53602, HS |
Family and domain databases
Gene3Di | 3.30.230.10, 1 hit 3.30.70.890, 1 hit |
InterProi | View protein in InterPro IPR036554, GHMP_kinase_C_sf IPR006204, GHMP_kinase_N_dom IPR005935, Mev_decarb IPR029765, Mev_diP_decarb IPR041431, Mvd1_C IPR020568, Ribosomal_S5_D2-typ_fold IPR014721, Ribosomal_S5_D2-typ_fold_subgr |
Pfami | View protein in Pfam PF00288, GHMP_kinases_N, 1 hit PF18376, MDD_C, 1 hit |
PIRSFi | PIRSF015950, Mev_P_decrbx, 1 hit |
SUPFAMi | SSF54211, SSF54211, 1 hit SSF55060, SSF55060, 1 hit |
TIGRFAMsi | TIGR01240, mevDPdecarb, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MVD1_HUMAN | |
Accessioni | P53602Primary (citable) accession number: P53602 Secondary accession number(s): Q53Y65 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | October 1, 1996 | |
Last modified: | December 2, 2020 | |
This is version 173 of the entry and version 1 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 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 - SIMILARITY comments
Index of protein domains and families - Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations