P53602 (MVD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	400 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Cholesterol biosynthesis Cholesterol metabolism Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Lyase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol biosynthetic process Non-traceable author statement PubMed 14680974. Source: UniProtKB 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
Cellular_component	cytosol Inferred from direct assay PubMed 14972328. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 400

400

Diphosphomevalonate decarboxylase

PRO_0000087012

Amino acid modifications

Modified residue

96

1

Phosphoserine Ref.6

Natural variations

Natural variant

278

1

N → H.
Corresponds to variant rs34519538 [ dbSNP | Ensembl ].

VAR_051605

Experimental info

Mutagenesis

17

1

N → A: 15-fold inflation in K(m) for mevalonate diphosphate. Ref.8

Mutagenesis

161

1

R → Q: 1000-fold diminution in specific activity. Ref.8

Secondary structure

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400

Helix Strand Turn

Details...

Beta strand

10 – 14

5

Beta strand

17 – 21

5

Beta strand

26 – 28

3

Turn

29 – 32

4

Beta strand

33 – 36

4

Beta strand

38 – 43

6

Turn

45 – 47

3

Beta strand

50 – 56

7

Beta strand

64 – 67

4

Helix

77 – 88

12

Beta strand

110 – 118

9

Turn

120 – 122

3

Helix

126 – 139

14

Turn

140 – 143

4

Helix

149 – 155

7

Helix

157 – 163

7

Beta strand

164 – 170

7

Beta strand

178 – 180

3

Beta strand

183 – 187

5

Helix

189 – 191

3

Beta strand

195 – 202

8

Helix

211 – 221

11

Helix

223 – 231

9

Helix

233 – 245

13

Helix

249 – 268

20

Beta strand

270 – 272

3

Helix

279 – 295

17

Beta strand

300 – 303

4

Beta strand

306 – 308

3

Beta strand

310 – 315

6

Helix

316 – 318

3

Helix

319 – 329

11

Turn

337 – 339

3

Beta strand

340 – 343

4

Helix

352 – 358

7

Beta strand

366 – 375

10

Helix

385 – 387

3

Beta strand

392 – 394

3

Sequences

	Sequence		Length	Mass (Da)
	P53602 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 3FD4741BCC4B68D8	FASTA	400	43,405
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"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].
[8]	"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.

IPI

IPI00022745.

RefSeq

NP_002452.1. NM_002461.1.

UniGene

Hs.252457.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3D4J	X-ray	2.40	A/B	1-400	[»]

ProteinModelPortal

P53602.

ModBase

Search...

Protein-protein interaction databases

IntAct

P53602. 3 interactions.

MINT

MINT-5004338.

STRING

9606.ENSP00000301012.

PTM databases

PhosphoSite

P53602.

Polymorphism databases

DMDM

1706681.

Proteomic databases

PaxDb

P53602.

PRIDE

P53602.

Protocols and materials databases

DNASU

4597.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301012; ENSP00000301012; ENSG00000167508.

GeneID

4597.

KEGG

hsa:4597.

UCSC

uc002flf.1. human.

Organism-specific databases

CTD

4597.

GeneCards

GC16M088718.

HGNC

HGNC:7529. MVD.

HPA

HPA041404.
HPA048250.

MIM

603236. gene.

neXtProt

NX_P53602.

PharmGKB

PA31330.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG3407.

HOVERGEN

HBG051503.

InParanoid

P53602.

KO

K01597.

OMA

GIECYYT.

OrthoDB

EOG4CZBG5.

PhylomeDB

P53602.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000167508-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P53602.

UniPathway

UPA00063.

Gene expression databases

ArrayExpress

P53602.

Bgee

P53602.

CleanEx

HS_MVD.

Genevestigator

P53602.

GermOnline

ENSG00000167508. Homo sapiens.

Family and domain databases

Gene3D

3.30.230.10. 1 hit.

InterPro

IPR006204. GHMP_kinase_N_dom.
IPR005935. Mev_diP_decarb.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
[Graphical view]

PANTHER

PTHR10977. PTHR10977. 1 hit.

Pfam

PF00288. GHMP_kinases_N. 1 hit.
[Graphical view]

PIRSF

PIRSF015950. Mev_P_decrbx. 1 hit.

SUPFAM

SSF54211. Ribosomal_S5_D2-typ_fold. 1 hit.

TIGRFAMs

TIGR01240. mevDPdecarb. 1 hit.

ProtoNet

Search...

Other

BindingDB

P53602.

ChEMBL

CHEMBL4340.

ChiTaRS

MVD. human.

EvolutionaryTrace

P53602.

GenomeRNAi

4597.

NextBio

17676.

SOURCE

Search...

Entry information

Entry name

MVD1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.