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Protein

Diphosphomevalonate decarboxylase

Gene

MVD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Performs the first committed step in the biosynthesis of isoprenes.

Catalytic activityi

ATP + (R)-5-diphosphomevalonate = ADP + phosphate + isopentenyl diphosphate + CO2.1 Publication

Kineticsi

  1. KM=7.4 µM for (R)-5-diphosphomevalonate1 Publication
  2. KM=0.32 mM for ATP1 Publication

    Pathwayi: cholesterol biosynthesis

    This protein is involved in the pathway cholesterol biosynthesis, which is part of Steroid biosynthesis.
    View all proteins of this organism that are known to be involved in the pathway cholesterol biosynthesis and in Steroid biosynthesis.

    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: UniProtKB
    • dolichyl diphosphate biosynthetic process Source: Reactome
    • isopentenyl diphosphate biosynthetic process, mevalonate pathway Source: GO_Central
    • isoprenoid biosynthetic process Source: UniProtKB
    • positive regulation of cell proliferation Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Biological processi

    Cholesterol biosynthesis, Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000167508-MONOMER.
    ZFISH:ENSG00000167508-MONOMER.
    BRENDAi4.1.1.33. 2681.
    ReactomeiR-HSA-191273. Cholesterol biosynthesis.
    R-HSA-2426168. Activation of gene expression by SREBF (SREBP).
    R-HSA-446199. Synthesis of Dolichyl-phosphate.
    SABIO-RKP53602.
    UniPathwayiUPA00063.

    Chemistry databases

    SwissLipidsiSLP:000001242.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Diphosphomevalonate decarboxylase (EC:4.1.1.33)
    Alternative name(s):
    Mevalonate (diphospho)decarboxylase
    Short name:
    MDDase
    Mevalonate pyrophosphate decarboxylase
    Gene namesi
    Name:MVD
    Synonyms:MPD
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:7529. MVD.

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: UniProtKB
    Complete GO annotation...

    Pathology & Biotechi

    Involvement in diseasei

    Porokeratosis 7, multiple types (POROK7)1 Publication
    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.
    See also OMIM:614714
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_075052101P → R in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant rs200033380dbSNPEnsembl.1
    Natural variantiVAR_075053128A → V in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant rs776358937dbSNPEnsembl.1
    Natural variantiVAR_075054161R → L in POROK7; unknown pathological significance. 1 Publication1
    Natural variantiVAR_075055161R → Q in POROK7; 1000-fold diminution in specific activity. 2 PublicationsCorresponds to variant rs144010349dbSNPEnsembl.1
    Natural variantiVAR_075056228R → Q in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant rs770939767dbSNPEnsembl.1
    Natural variantiVAR_075057228R → W in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant rs776684503dbSNPEnsembl.1
    Natural variantiVAR_075058249F → S in POROK7. 1 PublicationCorresponds to variant rs761991070dbSNPEnsembl.1
    Natural variantiVAR_075059292N → S in POROK7. 1 PublicationCorresponds to variant rs755948940dbSNPEnsembl.1
    Natural variantiVAR_075060371Missing in POROK7; unknown pathological significance. 1 Publication1
    Natural variantiVAR_075061376G → R in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant rs546127665dbSNPEnsembl.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi17N → A: 15-fold inflation in K(m) for mevalonate diphosphate. 1 Publication1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi4597.
    MIMi614714. phenotype.
    OpenTargetsiENSG00000167508.
    PharmGKBiPA31330.

    Chemistry databases

    ChEMBLiCHEMBL4340.
    GuidetoPHARMACOLOGYi642.

    Polymorphism and mutation databases

    BioMutaiMVD.
    DMDMi1706681.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedCombined sources
    ChainiPRO_00000870122 – 400Diphosphomevalonate decarboxylaseAdd BLAST399

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylalanineCombined sources1
    Modified residuei96PhosphoserineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiP53602.
    MaxQBiP53602.
    PaxDbiP53602.
    PeptideAtlasiP53602.
    PRIDEiP53602.

    PTM databases

    iPTMnetiP53602.
    PhosphoSitePlusiP53602.

    Expressioni

    Tissue specificityi

    Expressed in heart, skeletal muscle, lung, liver, brain, pancreas, kidney and placenta.1 Publication

    Gene expression databases

    BgeeiENSG00000167508.
    CleanExiHS_MVD.
    ExpressionAtlasiP53602. baseline and differential.
    GenevisibleiP53602. HS.

    Organism-specific databases

    HPAiHPA041404.
    HPA048250.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    GO - Molecular functioni

    • Hsp70 protein binding Source: UniProtKB
    • protein homodimerization activity Source: UniProtKB

    Protein-protein interaction databases

    BioGridi110682. 35 interactors.
    IntActiP53602. 9 interactors.
    MINTiMINT-5004338.
    STRINGi9606.ENSP00000301012.

    Chemistry databases

    BindingDBiP53602.

    Structurei

    Secondary structure

    1400
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi10 – 14Combined sources5
    Beta strandi17 – 21Combined sources5
    Beta strandi26 – 28Combined sources3
    Turni29 – 32Combined sources4
    Beta strandi33 – 36Combined sources4
    Beta strandi38 – 43Combined sources6
    Turni45 – 47Combined sources3
    Beta strandi50 – 56Combined sources7
    Beta strandi64 – 67Combined sources4
    Helixi77 – 88Combined sources12
    Beta strandi110 – 118Combined sources9
    Turni120 – 122Combined sources3
    Helixi126 – 139Combined sources14
    Turni140 – 143Combined sources4
    Helixi149 – 155Combined sources7
    Helixi157 – 163Combined sources7
    Beta strandi164 – 170Combined sources7
    Beta strandi178 – 180Combined sources3
    Beta strandi183 – 187Combined sources5
    Helixi189 – 191Combined sources3
    Beta strandi195 – 202Combined sources8
    Helixi211 – 221Combined sources11
    Helixi223 – 231Combined sources9
    Helixi233 – 245Combined sources13
    Helixi249 – 268Combined sources20
    Beta strandi270 – 272Combined sources3
    Helixi279 – 295Combined sources17
    Beta strandi300 – 303Combined sources4
    Beta strandi306 – 308Combined sources3
    Beta strandi310 – 315Combined sources6
    Helixi316 – 318Combined sources3
    Helixi319 – 329Combined sources11
    Turni337 – 339Combined sources3
    Beta strandi340 – 343Combined sources4
    Helixi352 – 358Combined sources7
    Beta strandi366 – 375Combined sources10
    Helixi385 – 387Combined sources3
    Beta strandi392 – 394Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3D4JX-ray2.40A/B1-400[»]
    ProteinModelPortaliP53602.
    SMRiP53602.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP53602.

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG2833. Eukaryota.
    COG3407. LUCA.
    GeneTreeiENSGT00390000015359.
    HOVERGENiHBG051503.
    InParanoidiP53602.
    KOiK01597.
    OMAiGIECYYT.
    OrthoDBiEOG091G0EUU.
    PhylomeDBiP53602.
    TreeFamiTF105952.

    Family and domain databases

    Gene3Di3.30.230.10. 1 hit.
    3.30.70.890. 1 hit.
    InterProiIPR013750. GHMP_kinase_C_dom.
    IPR006204. GHMP_kinase_N_dom.
    IPR005935. Mev_decarb.
    IPR029765. Mev_diP_decarb.
    IPR020568. Ribosomal_S5_D2-typ_fold.
    IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
    [Graphical view]
    PANTHERiPTHR10977. PTHR10977. 1 hit.
    PfamiPF00288. GHMP_kinases_N. 1 hit.
    [Graphical view]
    PIRSFiPIRSF015950. Mev_P_decrbx. 1 hit.
    SUPFAMiSSF54211. SSF54211. 1 hit.
    SSF55060. SSF55060. 1 hit.
    TIGRFAMsiTIGR01240. mevDPdecarb. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P53602-1 [UniParc]FASTAAdd to basket

    « Hide

            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
    Length:400
    Mass (Da):43,405
    Last modified:October 1, 1996 - v1
    Checksum:i3FD4741BCC4B68D8
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_075052101P → R in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant rs200033380dbSNPEnsembl.1
    Natural variantiVAR_075053128A → V in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant rs776358937dbSNPEnsembl.1
    Natural variantiVAR_075054161R → L in POROK7; unknown pathological significance. 1 Publication1
    Natural variantiVAR_075055161R → Q in POROK7; 1000-fold diminution in specific activity. 2 PublicationsCorresponds to variant rs144010349dbSNPEnsembl.1
    Natural variantiVAR_075056228R → Q in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant rs770939767dbSNPEnsembl.1
    Natural variantiVAR_075057228R → W in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant rs776684503dbSNPEnsembl.1
    Natural variantiVAR_075058249F → S in POROK7. 1 PublicationCorresponds to variant rs761991070dbSNPEnsembl.1
    Natural variantiVAR_051605278N → H.Corresponds to variant rs34519538dbSNPEnsembl.1
    Natural variantiVAR_075059292N → S in POROK7. 1 PublicationCorresponds to variant rs755948940dbSNPEnsembl.1
    Natural variantiVAR_075060371Missing in POROK7; unknown pathological significance. 1 Publication1
    Natural variantiVAR_075061376G → R in POROK7; unknown pathological significance. 1 PublicationCorresponds to variant rs546127665dbSNPEnsembl.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.
    CCDSiCCDS10968.1.
    RefSeqiNP_002452.1. NM_002461.2.
    UniGeneiHs.252457.

    Genome annotation databases

    EnsembliENST00000301012; ENSP00000301012; ENSG00000167508.
    GeneIDi4597.
    KEGGihsa:4597.
    UCSCiuc002flg.2. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    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.
    CCDSiCCDS10968.1.
    RefSeqiNP_002452.1. NM_002461.2.
    UniGeneiHs.252457.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3D4JX-ray2.40A/B1-400[»]
    ProteinModelPortaliP53602.
    SMRiP53602.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi110682. 35 interactors.
    IntActiP53602. 9 interactors.
    MINTiMINT-5004338.
    STRINGi9606.ENSP00000301012.

    Chemistry databases

    BindingDBiP53602.
    ChEMBLiCHEMBL4340.
    GuidetoPHARMACOLOGYi642.
    SwissLipidsiSLP:000001242.

    PTM databases

    iPTMnetiP53602.
    PhosphoSitePlusiP53602.

    Polymorphism and mutation databases

    BioMutaiMVD.
    DMDMi1706681.

    Proteomic databases

    EPDiP53602.
    MaxQBiP53602.
    PaxDbiP53602.
    PeptideAtlasiP53602.
    PRIDEiP53602.

    Protocols and materials databases

    DNASUi4597.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000301012; ENSP00000301012; ENSG00000167508.
    GeneIDi4597.
    KEGGihsa:4597.
    UCSCiuc002flg.2. human.

    Organism-specific databases

    CTDi4597.
    DisGeNETi4597.
    GeneCardsiMVD.
    HGNCiHGNC:7529. MVD.
    HPAiHPA041404.
    HPA048250.
    MIMi603236. gene.
    614714. phenotype.
    neXtProtiNX_P53602.
    OpenTargetsiENSG00000167508.
    PharmGKBiPA31330.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2833. Eukaryota.
    COG3407. LUCA.
    GeneTreeiENSGT00390000015359.
    HOVERGENiHBG051503.
    InParanoidiP53602.
    KOiK01597.
    OMAiGIECYYT.
    OrthoDBiEOG091G0EUU.
    PhylomeDBiP53602.
    TreeFamiTF105952.

    Enzyme and pathway databases

    UniPathwayiUPA00063.
    BioCyciMetaCyc:ENSG00000167508-MONOMER.
    ZFISH:ENSG00000167508-MONOMER.
    BRENDAi4.1.1.33. 2681.
    ReactomeiR-HSA-191273. Cholesterol biosynthesis.
    R-HSA-2426168. Activation of gene expression by SREBF (SREBP).
    R-HSA-446199. Synthesis of Dolichyl-phosphate.
    SABIO-RKP53602.

    Miscellaneous databases

    ChiTaRSiMVD. human.
    EvolutionaryTraceiP53602.
    GenomeRNAii4597.
    PROiP53602.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000167508.
    CleanExiHS_MVD.
    ExpressionAtlasiP53602. baseline and differential.
    GenevisibleiP53602. HS.

    Family and domain databases

    Gene3Di3.30.230.10. 1 hit.
    3.30.70.890. 1 hit.
    InterProiIPR013750. GHMP_kinase_C_dom.
    IPR006204. GHMP_kinase_N_dom.
    IPR005935. Mev_decarb.
    IPR029765. Mev_diP_decarb.
    IPR020568. Ribosomal_S5_D2-typ_fold.
    IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
    [Graphical view]
    PANTHERiPTHR10977. PTHR10977. 1 hit.
    PfamiPF00288. GHMP_kinases_N. 1 hit.
    [Graphical view]
    PIRSFiPIRSF015950. Mev_P_decrbx. 1 hit.
    SUPFAMiSSF54211. SSF54211. 1 hit.
    SSF55060. SSF55060. 1 hit.
    TIGRFAMsiTIGR01240. mevDPdecarb. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiMVD1_HUMAN
    AccessioniPrimary (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: November 2, 2016
    This is version 148 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.