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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	400 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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 Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Lyase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Non-traceable author statement. Source: UniProtKB positive regulation of cell proliferation Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW Hsp70 protein binding Inferred from physical interaction. Source: UniProtKB diphosphomevalonate decarboxylase activity Inferred from direct assay. Source: UniProtKB kinase activity Inferred from electronic annotation. Source: InterPro 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

Initiator methionine

1

1

Removed

Chain

2 – 400

399

Diphosphomevalonate decarboxylase

PRO_0000087012

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.8

Modified residue

96

1

Phosphoserine Ref.6 Ref.7

Natural variations

Natural variant

278

1

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

VAR_051605

Secondary structure

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400

Helix Strand Turn

Details...

Beta strand

10 – 14

5

Beta strand

17 – 21

5

Turn

29 – 32

4

Beta strand

38 – 42

5

Turn

45 – 47

3

Beta strand

50 – 56

7

Beta strand

64 – 67

4

Helix

77 – 88

12

Beta strand

110 – 118

9

Turn

126 – 128

3

Helix

132 – 139

8

Helix

149 – 153

5

Helix

159 – 163

5

Beta strand

168 – 170

3

Beta strand

183 – 187

5

Helix

189 – 191

3

Beta strand

195 – 201

7

Helix

216 – 221

6

Helix

223 – 231

9

Helix

233 – 245

13

Helix

249 – 268

20

Beta strand

270 – 272

3

Helix

279 – 294

16

Beta strand

300 – 303

4

Beta strand

310 – 315

6

Helix

316 – 318

3

Helix

319 – 327

9

Beta strand

339 – 341

3

Helix

352 – 358

7

Beta strand

369 – 374

6

Helix

385 – 387

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: 8626466] [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: 15489334] [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: 9392419] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[6]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[7]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[9]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	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.

SMR

P53602. Positions 8-396.

ModBase

Search...

Protein-protein interaction databases

IntAct

P53602. 3 interactions.

MINT

MINT-5004338.

STRING

P53602.

PTM databases

PhosphoSite

P53602.

Polymorphism databases

DMDM

1706681.

Proteomic databases

PRIDE

P53602.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301012; ENSP00000301012; ENSG00000167508.

GeneID

4597.

KEGG

hsa:4597.

NMPDR

fig|9606.3.peg.12716.

UCSC

uc002flg.1. human.

Organism-specific databases

CTD

4597.

GeneCards

GC16M088718.

H-InvDB

HIX0202291.

HGNC

HGNC:7529. MVD.

MIM

603236. gene.

neXtProt

NX_P53602.

PharmGKB

PA31330.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04954.

GeneTree

ENSGT00390000015359.

HOGENOM

HBG502799.

HOVERGEN

HBG051503.

InParanoid

P53602.

OMA

FGGYVAW.

OrthoDB

EOG4CZBG5.

PhylomeDB

P53602.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000167508-MONOMER.

Reactome

REACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

P53602.

Bgee

P53602.

CleanEx

HS_MVD.

Genevestigator

P53602.

GermOnline

ENSG00000167508. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:3.30.230.10. Ribosomal_S5_D2-type_fold. 1 hit.

KO

K01597.

PANTHER

PTHR10977. Mev_diP_decarb. 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

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:	January 25, 2012
This is version 103 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.