Q03426 (KIME_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mevalonate kinase
Short name=MK
EC=2.7.1.36

Gene names

Name:

MVK

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	396 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be a regulatory site in cholesterol biosynthetic pathway.
Catalytic activity	ATP + (R)-mevalonate = ADP + (R)-5-phosphomevalonate.
Enzyme regulation	Farnesyl- and geranyl-pyrophosphates are competitive inhibitors.
Pathway	Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: step 1/3.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm. Peroxisome.
Involvement in disease	Defects in MVK are the cause of mevalonic aciduria (MEVA) [MIM:610377]. It is an accumulation of mevalonic acid which causes a variety of symptoms such as psychomotor retardation, dysmorphic features, cataracts, hepatosplenomegaly, lymphadenopathy, anemia, hypotonia, myopathy, and ataxia. Ref.1 Ref.3 Ref.7 Ref.8 Ref.11 Defects in MVK are the cause of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) [MIM:260920]. HIDS is an autosomal recessive disease characterized by recurrent episodes of unexplained high fever associated with skin rash, diarrhea, adenopathy (swollen, tender lymph nodes), athralgias and/or arthritis. Concentration of IgD, and often IgA, are above normal. Ref.3 Ref.9 Ref.10 Ref.11 Ref.12
Sequence similarities	Belongs to the GHMP kinase family. Mevalonate kinase subfamily.
Sequence caution	The sequence CAA53059.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Cytoplasm Peroxisome
Coding sequence diversity	Polymorphism
Disease	Cataract Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Traceable author statement. Source: Reactome isoprenoid biosynthetic process Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: Reactome peroxisome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW identical protein binding Inferred from physical interaction. Source: IntAct mevalonate kinase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-740630,EBI-740630

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 396

396

Mevalonate kinase

PRO_0000156657

Regions

Nucleotide binding

138 – 148

11

ATP By similarity

Sites

Binding site

55

1

ATP By similarity

Binding site

135

1

ATP By similarity

Natural variations

Natural variant

20

1

H → N in HIDS. Ref.11
Corresponds to variant rs11544299 [ dbSNP | Ensembl ].

VAR_010956

Natural variant

20

1

H → P in HIDS and MEVA. Ref.3 Ref.9 Ref.11

VAR_004022

Natural variant

20

1

H → Q in HIDS. Ref.12

VAR_029519

Natural variant

39

1

L → P in HIDS. Ref.3 Ref.11

VAR_010957

Natural variant

52

1

S → N. Ref.11 Ref.12
Corresponds to variant rs7957619 [ dbSNP | Ensembl ].

VAR_010958

Natural variant

132

1

V → I in HIDS. Ref.12

VAR_029520

Natural variant

135

1

S → L in HIDS. Ref.3

VAR_010959

Natural variant

148

1

A → T in HIDS. Ref.3 Ref.12

VAR_010960

Natural variant

150

1

S → L in HIDS. Ref.11

VAR_010961

Natural variant

167

1

P → L in HIDS. Ref.10 Ref.11

VAR_004023

Natural variant

171

1

G → R in HIDS. Ref.12

VAR_029521

Natural variant

202

1

G → R in HIDS. Ref.11

VAR_010962

Natural variant

211

1

G → E in HIDS. Ref.12

VAR_029522

Natural variant

215

1

R → Q in HIDS. Ref.11 Ref.12

VAR_010963

Natural variant

243

1

T → I in MEVA. Ref.7

VAR_010964

Natural variant

250

1

V → I in HIDS. Ref.12

VAR_029523

Natural variant

264

1

L → F in MEVA. Ref.3 Ref.7

VAR_010965

Natural variant

265

1

L → P in MEVA. Ref.7

VAR_010966

Natural variant

265

1

L → R in HIDS. Ref.12

VAR_029524

Natural variant

268

1

I → T in HIDS and MEVA. Ref.3 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12

VAR_004024

Natural variant

301

1

N → T in MEVA; diminished activity. Ref.1
Corresponds to variant rs28934896 [ dbSNP | Ensembl ].

VAR_004025

Natural variant

309

1

G → S in HIDS. Ref.11

VAR_010967

Natural variant

310

1

V → M in MEVA and HIDS. Ref.3 Ref.8 Ref.12

VAR_009068

Natural variant

326

1

G → R in HIDS. Ref.11

VAR_010968

Natural variant

334

1

A → T in MEVA. Ref.3 Ref.8 Ref.11

VAR_004026

Natural variant

335

1

G → S.
Corresponds to variant rs11614976 [ dbSNP | Ensembl ].

VAR_029525

Natural variant

356

1

T → M. Ref.12

VAR_029526

Natural variant

376

1

G → V in HIDS. Ref.12

VAR_029527

Natural variant

377

1

V → I in HIDS; most frequent mutation. Ref.3 Ref.9 Ref.10 Ref.11 Ref.12
Corresponds to variant rs28934897 [ dbSNP | Ensembl ].

VAR_004027

Secondary structure

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396

Helix Strand Turn

Details...

Beta strand

4 – 10

7

Beta strand

14 – 17

4

Beta strand

28 – 31

4

Beta strand

37 – 43

7

Beta strand

49 – 52

4

Beta strand

59 – 62

4

Helix

64 – 69

6

Helix

85 – 94

10

Helix

103 – 119

17

Beta strand

122 – 125

4

Beta strand

129 – 137

9

Helix

146 – 160

15

Helix

179 – 190

12

Turn

194 – 196

3

Helix

204 – 209

6

Beta strand

214 – 216

3

Beta strand

221 – 223

3

Beta strand

230 – 236

7

Helix

243 – 247

5

Helix

251 – 256

6

Helix

258 – 278

21

Helix

288 – 307

20

Helix

313 – 323

11

Helix

350 – 361

12

Beta strand

366 – 372

7

Beta strand

378 – 380

3

Helix

387 – 392

6

Sequences

	Sequence		Length	Mass (Da)
	Q03426 [UniParc]. Last modified October 1, 1993. Version 1. Checksum: C8F6B629B58CD229	FASTA	396	42,451
	10 20 30 40 50 60 MLSEVLLVSA PGKVILHGEH AVVHGKVALA VSLNLRTFLR LQPHSNGKVD LSLPNIGIKR 70 80 90 100 110 120 AWDVARLQSL DTSFLEQGDV TTPTSEQVEK LKEVAGLPDD CAVTERLAVL AFLYLYLSIC 130 140 150 160 170 180 RKQRALPSLD IVVWSELPPG AGLGSSAAYS VCLAAALLTV CEEIPNPLKD GDCVNRWTKE 190 200 210 220 230 240 DLELINKWAF QGERMIHGNP SGVDNAVSTW GGALRYHQGK ISSLKRSPAL QILLTNTKVP 250 260 270 280 290 300 RNTRALVAGV RNRLLKFPEI VAPLLTSIDA ISLECERVLG EMGEAPAPEQ YLVLEELIDM 310 320 330 340 350 360 NQHHLNALGV GHASLDQLCQ VTRARGLHSK LTGAGGGGCG ITLLKPGLEQ PEVEATKQAL 370 380 390 TSCGFDCLET SIGAPGVSIH SATSLDSRVQ QALDGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of human mevalonate kinase and identification of a missense mutation in the genetic disease mevalonic aciduria." Schafer B.L., Bishop R.W., Kratunis V.J., Kalinowski S.S., Mosley S.T., Gibson K.M., Tanaka R.D. J. Biol. Chem. 267:13229-13238(1992) [PubMed: 1377680] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MEVA THR-301.
[2]	"Insertional activation of mevalonate kinase by hepatitis B virus DNA in a human hepatoma cell line." Graef E., Caselmann W.H., Wells J., Koshy R. Oncogene 9:81-87(1994) [PubMed: 8302606] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hepatoma.
[3]	"Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome." Houten S.M., Koster J., Romeijn G.-J., Frenkel J., Di Rocco M., Caruso U., Landrieu P., Kelley R.I., Kuis W., Poll-The B.T., Gibson K.M., Wanders R.J.A., Waterham H.R. Eur. J. Hum. Genet. 9:253-259(2001) [PubMed: 11313768] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIDS PRO-20; PRO-39; LEU-135; THR-148; THR-268 AND ILE-377, VARIANTS MEVA PRO-20; PHE-264; THR-268; MET-310 AND THR-334.
[4]	Erratum Houten S.M., Koster J., Romeijn G.-J., Frenkel J., Di Rocco M., Caruso U., Landrieu P., Kelley R.I., Kuis W., Poll-The B.T., Gibson K.M., Wanders R.J.A., Waterham H.R. Eur. J. Hum. Genet. 9:651-651(2001)
[5]	"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: Skin.
[6]	"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].
[7]	"Identification of a mutation cluster in mevalonate kinase deficiency, including a new mutation in a patient of Mennonite ancestry." Hinson D.D., Ross R.M., Krisans S., Shaw J.L., Kozich V., Rolland M.-O., Divry P., Mancini J., Hoffmann G.F., Gibson K.M. Am. J. Hum. Genet. 65:327-335(1999) [PubMed: 10417275] [Abstract] Cited for: VARIANTS MEVA ILE-243; PHE-264; PRO-265 AND THR-268.
[8]	"Identification and characterization of three novel missense mutations in mevalonate kinase cDNA causing mevalonic aciduria, a disorder of isoprene biosynthesis." Houten S.M., Romeijn G.J., Koster J., Gray R.G.F., Darbyshire P., Smit G.P.A., de Klerk J.B.C., Duran R., Gibson K.M., Wanders R.J.A., Waterham H.R. Hum. Mol. Genet. 8:1523-1528(1999) [PubMed: 10401001] [Abstract] Cited for: VARIANTS MEVA MET-310 AND THR-334.
[9]	"Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome." Houten S.M., Kuis W., Duran M., de Koning T.J., van Royen-Kerkhof A., Romeijn G.J., Frenkel J., Dorland L., de Barse M.M.J., Huijbers W.A.R., Rijkers G.T., Waterham H.R., Wanders R.J.A., Poll-The B.T. Nat. Genet. 22:175-177(1999) [PubMed: 10369261] [Abstract] Cited for: VARIANTS HIDS PRO-20; THR-268 AND ILE-377.
[10]	"Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome." Drenth J.P.H., Cuisset L., Grateau G., Vasseur C., van der Velde-Visser S.D., de Jong J.G.N., Beckmann J.S., van der Meer J.W.M., Delpech M. Nat. Genet. 22:178-181(1999) [PubMed: 10369262] [Abstract] Cited for: VARIANTS HIDS LEU-167; THR-268 AND ILE-377.
[11]	"Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome." Cuisset L., Drenth J.P.H., Simon A., Vincent M.-F., van der Velde-Visser S.D., van der Meer J.W.M., Grateau G., Delpech M. Eur. J. Hum. Genet. 9:260-266(2001) [PubMed: 11313769] [Abstract] Cited for: VARIANTS HIDS ASN-20; PRO-20; PRO-39; LEU-150; LEU-167; ARG-202; GLN-215; THR-268; SER-309; ARG-326 AND ILE-377, VARIANT MEVA THR-334, VARIANT ASN-52.
[12]	"MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever." D'Osualdo A., Picco P., Caroli F., Gattorno M., Giacchino R., Fortini P., Corona F., Tommasini A., Salvi G., Specchia F., Obici L., Meini A., Ricci A., Seri M., Ravazzolo R., Martini A., Ceccherini I. Eur. J. Hum. Genet. 13:314-320(2005) [PubMed: 15536479] [Abstract] Cited for: VARIANTS HIDS GLN-20; ILE-132; THR-148; ARG-171; GLU-211; GLN-215; ILE-250; ARG-265; THR-268; MET-310; VAL-376 AND ILE-377, VARIANTS ASN-52 AND MET-356.
+	Additional computationally mapped references.

Web resources

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M88468 mRNA. Translation: AAB59362.1.
X75311 mRNA. Translation: CAA53060.1.
X75311 mRNA. Translation: CAA53059.1. Different initiation.
AF217535 , AF217528, AF217529, AF217530, AF217531, AF217532, AF217533, AF217534 Genomic DNA. Translation: AAF82407.1.
BC016140 mRNA. Translation: AAH16140.1.

IPI

IPI00010717.

PIR

A42919.

RefSeq

NP_000422.1. NM_000431.2.
NP_001107657.1. NM_001114185.1.

UniGene

Hs.130607.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2R3V	X-ray	2.50	A/B/C/D	1-396	[»]

ProteinModelPortal

Q03426.

SMR

Q03426. Positions 2-395.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q03426. 2 interactions.

MINT

MINT-1473671.

STRING

Q03426.

PTM databases

PhosphoSite

Q03426.

Polymorphism databases

DMDM

417215.

Proteomic databases

PRIDE

Q03426.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000228510; ENSP00000228510; ENSG00000110921.
ENST00000392727; ENSP00000376487; ENSG00000110921.
ENST00000447878; ENSP00000415555; ENSG00000110921.

GeneID

4598.

KEGG

hsa:4598.

NMPDR

fig|9606.3.peg.8216.

UCSC

uc001toy.2. human.

Organism-specific databases

CTD

4598.

GeneCards

GC12P110012.

H-InvDB

HIX0010979.

HGNC

HGNC:7530. MVK.

HPA

HPA016961.

MIM

251170. gene.
260920. phenotype.
610377. phenotype.

neXtProt

NX_Q03426.

Orphanet

343. Hyperimmunoglobinemia D with recurrent fever.
29. Mevalonic aciduria.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG11699.

HOVERGEN

HBG000402.

InParanoid

Q03426.

OMA

TVCEEIP.

PhylomeDB

Q03426.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000110921-MONOMER.

Reactome

REACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

Q03426.

Bgee

Q03426.

CleanEx

HS_MVK.

Genevestigator

Q03426.

GermOnline

ENSG00000110921. Homo sapiens.

Family and domain databases

InterPro

IPR006204. GHMP_kinase.
IPR013750. GHMP_kinase_C.
IPR006203. GHMP_knse_ATP-bd_CS.
IPR006205. Mev_gal_kin.
IPR006206. Mevalonate/galactokinase.
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

K00869.

Pfam

PF08544. GHMP_kinases_C. 1 hit.
PF00288. GHMP_kinases_N. 1 hit.
[Graphical view]

PRINTS

PR00959. MEVGALKINASE.

SUPFAM

SSF54211. Ribosomal_S5_D2-typ_fold. 1 hit.

TIGRFAMs

TIGR00549. Mevalon_kin. 1 hit.

PROSITE

PS00627. GHMP_KINASES_ATP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

17680.

SOURCE

Search...

Entry information

Entry name

KIME_HUMAN

Accession

Primary (citable) accession number: Q03426

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	October 1, 1993
Last modified:	January 25, 2012
This is version 136 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.