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P53602 (MVD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | 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:
Diphosphomevalonate decarboxylase

EC=4.1.1.33
Alternative name(s):
Mevalonate (diphospho)decarboxylase
Short name=MDDase
Mevalonate pyrophosphate decarboxylase
Gene names
Name:MVD
Synonyms:MPD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length400 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Performs the first committed step in the biosynthesis of isoprenes.

Catalytic activity

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

Pathway

Steroid biosynthesis; cholesterol biosynthesis.

Subunit structure

Homodimer. Ref.1

Tissue specificity

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

Sequence similarities

Belongs to the diphosphomevalonate decarboxylase family.

Biophysicochemical properties

Kinetic parameters:

KM=7.4 µM for (R)-5-diphosphomevalonate Ref.5

KM=0.32 mM for ATP

Ontologies

Keywords
   Biological processCholesterol biosynthesis
Cholesterol metabolism
Lipid biosynthesis
Lipid metabolism
Steroid biosynthesis
Steroid metabolism
Sterol biosynthesis
Sterol metabolism
   Coding sequence diversityPolymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionLyase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular protein metabolic process

Traceable author statement. Source: Reactome

cholesterol biosynthetic process

Non-traceable author statement PubMed 14680974. Source: UniProtKB

dolichol-linked oligosaccharide biosynthetic process

Traceable author statement. Source: Reactome

dolichyl diphosphate biosynthetic process

Traceable author statement. Source: Reactome

isoprenoid biosynthetic process

Inferred from direct assay PubMed 11792727PubMed 14680974. Source: UniProtKB

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 9270019. Source: UniProtKB

post-translational protein modification

Traceable author statement. Source: Reactome

protein N-linked glycosylation via asparagine

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Inferred from direct assay PubMed 14972328. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Hsp70 protein binding

Inferred from physical interaction PubMed 12646231. Source: UniProtKB

diphosphomevalonate decarboxylase activity

Inferred from direct assay PubMed 11792727PubMed 14680974. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.7
Chain2 – 400399Diphosphomevalonate decarboxylase
PRO_0000087012

Amino acid modifications

Modified residue21N-acetylalanine Ref.7 Ref.9
Modified residue961Phosphoserine Ref.6

Natural variations

Natural variant2781N → H.
Corresponds to variant rs34519538 [ dbSNP | Ensembl ].
VAR_051605

Experimental info

Mutagenesis171N → A: 15-fold inflation in K(m) for mevalonate diphosphate. Ref.10
Mutagenesis1611R → Q: 1000-fold diminution in specific activity. Ref.10

Secondary structure

...................................................................... 400
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P53602 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 3FD4741BCC4B68D8

FASTA40043,405
        10         20         30         40         50         60 
MASEKPLAAV TCTAPVNIAV IKYWGKRDEE LVLPINSSLS VTLHQDQLKT TTTAVISKDF 

        70         80         90        100        110        120 
TEDRIWLNGR EEDVGQPRLQ ACLREIRCLA RKRRNSRDGD PLPSSLSCKV HVASVNNFPT 

       130        140        150        160        170        180 
AAGLASSAAG YACLAYTLAR VYGVESDLSE VARRGSGSAC RSLYGGFVEW QMGEQADGKD 

       190        200        210        220        230        240 
SIARQVAPES HWPELRVLIL VVSAEKKLTG STVGMRASVE TSPLLRFRAE SVVPARMAEM 

       250        260        270        280        290        300 
ARCIRERDFP SFAQLTMKDS NQFHATCLDT FPPISYLNAI SWRIIHLVHR FNAHHGDTKV 

       310        320        330        340        350        360 
AYTFDAGPNA VIFTLDDTVA EFVAAVWHGF PPGSNGDTFL KGLQVRPAPL SAELQAALAM 

       370        380        390        400 
EPTPGGVKYI IVTQVGPGPQ ILDDPCAHLL GPDGLPKPAA 

« Hide

References

« Hide 'large scale' references
[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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"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]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U49260 mRNA. Translation: AAC50440.1.
BT006930 mRNA. Translation: AAP35576.1.
CH471184 Genomic DNA. Translation: EAW66792.1.
BC000011 mRNA. Translation: AAH00011.1.
CCDSCCDS10968.1.
RefSeqNP_002452.1. NM_002461.1.
UniGeneHs.252457.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3D4JX-ray2.40A/B1-400[»]
ProteinModelPortalP53602.
SMRP53602. Positions 8-396.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110682. 28 interactions.
IntActP53602. 3 interactions.
MINTMINT-5004338.
STRING9606.ENSP00000301012.

Chemistry

BindingDBP53602.
ChEMBLCHEMBL4340.
GuidetoPHARMACOLOGY642.

PTM databases

PhosphoSiteP53602.

Polymorphism databases

DMDM1706681.

Proteomic databases

MaxQBP53602.
PaxDbP53602.
PRIDEP53602.

Protocols and materials databases

DNASU4597.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000301012; ENSP00000301012; ENSG00000167508.
GeneID4597.
KEGGhsa:4597.
UCSCuc002flf.1. human.

Organism-specific databases

CTD4597.
GeneCardsGC16M088718.
HGNCHGNC:7529. MVD.
HPAHPA041404.
HPA048250.
MIM603236. gene.
neXtProtNX_P53602.
PharmGKBPA31330.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3407.
HOVERGENHBG051503.
InParanoidP53602.
KOK01597.
OMADTDPPIF.
OrthoDBEOG7K0ZCW.
PhylomeDBP53602.
TreeFamTF105952.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000167508-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_17015. Metabolism of proteins.
SABIO-RKP53602.
UniPathwayUPA00063.

Gene expression databases

ArrayExpressP53602.
BgeeP53602.
CleanExHS_MVD.
GenevestigatorP53602.

Family and domain databases

Gene3D3.30.230.10. 1 hit.
3.30.70.890. 1 hit.
InterProIPR013750. GHMP_kinase_C_dom.
IPR006204. GHMP_kinase_N_dom.
IPR005935. Mev_diP_decarb.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
[Graphical view]
PANTHERPTHR10977. PTHR10977. 1 hit.
PfamPF00288. GHMP_kinases_N. 1 hit.
[Graphical view]
PIRSFPIRSF015950. Mev_P_decrbx. 1 hit.
SUPFAMSSF54211. SSF54211. 1 hit.
SSF55060. SSF55060. 1 hit.
TIGRFAMsTIGR01240. mevDPdecarb. 1 hit.
ProtoNetSearch...

Other

ChiTaRSMVD. human.
EvolutionaryTraceP53602.
GenomeRNAi4597.
NextBio17676.
PROP53602.
SOURCESearch...

Entry information

Entry nameMVD1_HUMAN
AccessionPrimary (citable) accession number: P53602
Secondary accession number(s): Q53Y65
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 127 of the entry and version 1 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

SIMILARITY comments

Index of protein domains and families

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 16

Human chromosome 16: entries, gene names and cross-references to MIM