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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

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. diphosphomevalonate decarboxylase activity Source: UniProtKB
  3. Hsp70 protein binding Source: UniProtKB
  4. protein homodimerization activity Source: UniProtKB

GO - Biological processi

  1. cellular protein metabolic process Source: Reactome
  2. cholesterol biosynthetic process Source: UniProtKB
  3. dolichol-linked oligosaccharide biosynthetic process Source: Reactome
  4. dolichyl diphosphate biosynthetic process Source: Reactome
  5. isopentenyl diphosphate biosynthetic process, mevalonate pathway Source: InterPro
  6. isoprenoid biosynthetic process Source: UniProtKB
  7. positive regulation of cell proliferation Source: UniProtKB
  8. post-translational protein modification Source: Reactome
  9. protein N-linked glycosylation via asparagine Source: Reactome
  10. small molecule metabolic process Source: Reactome
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.
ReactomeiREACT_147904. Activation of gene expression by SREBF (SREBP).
REACT_22230. Synthesis of Dolichyl-phosphate.
REACT_9405. Cholesterol biosynthesis.
SABIO-RKP53602.
UniPathwayiUPA00063.

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
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:7529. MVD.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi17 – 171N → A: 15-fold inflation in K(m) for mevalonate diphosphate. 1 Publication
Mutagenesisi161 – 1611R → Q: 1000-fold diminution in specific activity. 1 Publication

Organism-specific databases

PharmGKBiPA31330.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed2 Publications
Chaini2 – 400399Diphosphomevalonate decarboxylasePRO_0000087012Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine2 Publications
Modified residuei96 – 961Phosphoserine1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP53602.
PaxDbiP53602.
PRIDEiP53602.

PTM databases

PhosphoSiteiP53602.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiP53602.
CleanExiHS_MVD.
ExpressionAtlasiP53602. baseline and differential.
GenevestigatoriP53602.

Organism-specific databases

HPAiHPA041404.
HPA048250.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi110682. 27 interactions.
IntActiP53602. 3 interactions.
MINTiMINT-5004338.
STRINGi9606.ENSP00000301012.

Structurei

Secondary structure

1
400
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi10 – 145Combined sources
Beta strandi17 – 215Combined sources
Beta strandi26 – 283Combined sources
Turni29 – 324Combined sources
Beta strandi33 – 364Combined sources
Beta strandi38 – 436Combined sources
Turni45 – 473Combined sources
Beta strandi50 – 567Combined sources
Beta strandi64 – 674Combined sources
Helixi77 – 8812Combined sources
Beta strandi110 – 1189Combined sources
Turni120 – 1223Combined sources
Helixi126 – 13914Combined sources
Turni140 – 1434Combined sources
Helixi149 – 1557Combined sources
Helixi157 – 1637Combined sources
Beta strandi164 – 1707Combined sources
Beta strandi178 – 1803Combined sources
Beta strandi183 – 1875Combined sources
Helixi189 – 1913Combined sources
Beta strandi195 – 2028Combined sources
Helixi211 – 22111Combined sources
Helixi223 – 2319Combined sources
Helixi233 – 24513Combined sources
Helixi249 – 26820Combined sources
Beta strandi270 – 2723Combined sources
Helixi279 – 29517Combined sources
Beta strandi300 – 3034Combined sources
Beta strandi306 – 3083Combined sources
Beta strandi310 – 3156Combined sources
Helixi316 – 3183Combined sources
Helixi319 – 32911Combined sources
Turni337 – 3393Combined sources
Beta strandi340 – 3434Combined sources
Helixi352 – 3587Combined sources
Beta strandi366 – 37510Combined sources
Helixi385 – 3873Combined sources
Beta strandi392 – 3943Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3D4JX-ray2.40A/B1-400[»]
ProteinModelPortaliP53602.
SMRiP53602. Positions 8-396.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP53602.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG3407.
GeneTreeiENSGT00390000015359.
HOVERGENiHBG051503.
InParanoidiP53602.
KOiK01597.
OMAiDTDPPIF.
OrthoDBiEOG7K0ZCW.
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti278 – 2781N → H.
Corresponds to variant rs34519538 [ dbSNP | Ensembl ].
VAR_051605

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_002461.1.
UniGeneiHs.252457.

Genome annotation databases

EnsembliENST00000301012; ENSP00000301012; ENSG00000167508.
GeneIDi4597.
KEGGihsa:4597.
UCSCiuc002flf.1. human.

Polymorphism databases

DMDMi1706681.

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_002461.1.
UniGeneiHs.252457.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3D4JX-ray2.40A/B1-400[»]
ProteinModelPortaliP53602.
SMRiP53602. Positions 8-396.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110682. 27 interactions.
IntActiP53602. 3 interactions.
MINTiMINT-5004338.
STRINGi9606.ENSP00000301012.

Chemistry

BindingDBiP53602.
ChEMBLiCHEMBL4340.
GuidetoPHARMACOLOGYi642.

PTM databases

PhosphoSiteiP53602.

Polymorphism databases

DMDMi1706681.

Proteomic databases

MaxQBiP53602.
PaxDbiP53602.
PRIDEiP53602.

Protocols and materials databases

DNASUi4597.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301012; ENSP00000301012; ENSG00000167508.
GeneIDi4597.
KEGGihsa:4597.
UCSCiuc002flf.1. human.

Organism-specific databases

CTDi4597.
GeneCardsiGC16M088718.
HGNCiHGNC:7529. MVD.
HPAiHPA041404.
HPA048250.
MIMi603236. gene.
neXtProtiNX_P53602.
PharmGKBiPA31330.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG3407.
GeneTreeiENSGT00390000015359.
HOVERGENiHBG051503.
InParanoidiP53602.
KOiK01597.
OMAiDTDPPIF.
OrthoDBiEOG7K0ZCW.
PhylomeDBiP53602.
TreeFamiTF105952.

Enzyme and pathway databases

UniPathwayiUPA00063.
BioCyciMetaCyc:ENSG00000167508-MONOMER.
ReactomeiREACT_147904. Activation of gene expression by SREBF (SREBP).
REACT_22230. Synthesis of Dolichyl-phosphate.
REACT_9405. Cholesterol biosynthesis.
SABIO-RKP53602.

Miscellaneous databases

ChiTaRSiMVD. human.
EvolutionaryTraceiP53602.
GenomeRNAii4597.
NextBioi17676.
PROiP53602.
SOURCEiSearch...

Gene expression databases

BgeeiP53602.
CleanExiHS_MVD.
ExpressionAtlasiP53602. baseline and differential.
GenevestigatoriP53602.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and expression of the cDNAs encoding human and yeast mevalonate pyrophosphate decarboxylase."
    Toth M.J., Huwyler L.
    J. Biol. Chem. 271:7895-7898(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, SUBUNIT, 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 (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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: Placenta.
  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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  7. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
    Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
    Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. "Human mevalonate diphosphate decarboxylase: characterization, investigation of the mevalonate diphosphate binding site, and crystal structure."
    Voynova N.E., Fu Z., Battaile K.P., Herdendorf T.J., Kim J.J., Miziorko H.M.
    Arch. Biochem. Biophys. 480:58-67(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), MUTAGENESIS OF ASN-17 AND ARG-161.

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: January 7, 2015
This is version 131 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

External Data

Dasty 3

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 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.