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Protein

Mevalonate kinase

Gene

Mvk

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May be a regulatory site in cholesterol biosynthetic pathway.

Catalytic activityi

ATP + (R)-mevalonate = ADP + (R)-5-phosphomevalonate.

Enzyme regulationi

Farnesyl- and geranyl-pyrophosphates are competitive inhibitors.

Pathwayi: isopentenyl diphosphate biosynthesis via mevalonate pathway

This protein is involved in step 1 of the subpathway that synthesizes isopentenyl diphosphate from (R)-mevalonate.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. Mevalonate kinase (Mvk)
  2. Phosphomevalonate kinase (Pmvk)
  3. no protein annotated in this organism
This subpathway is part of the pathway isopentenyl diphosphate biosynthesis via mevalonate pathway, which is itself part of Isoprenoid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes isopentenyl diphosphate from (R)-mevalonate, the pathway isopentenyl diphosphate biosynthesis via mevalonate pathway and in Isoprenoid biosynthesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei55 – 551ATP1 Publication
Binding sitei104 – 1041ATP1 Publication
Binding sitei108 – 1081ATP1 Publication
Binding sitei135 – 1351ATP1 Publication
Active sitei204 – 2041Proton acceptorBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi138 – 14811ATP1 PublicationAdd
BLAST

GO - Molecular functioni

  • ATP binding Source: RGD
  • mevalonate kinase activity Source: RGD
  • mRNA binding Source: RGD

GO - Biological processi

  • cholesterol biosynthetic process Source: RGD
  • isopentenyl diphosphate biosynthetic process, mevalonate pathway Source: RGD
  • isoprenoid biosynthetic process Source: RGD
  • isoprenoid metabolic process Source: RGD
  • negative regulation of translation Source: RGD
  • regulation of cholesterol biosynthetic process Source: RGD
  • sterol metabolic process Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

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

BRENDAi2.7.1.36. 5301.
SABIO-RKP17256.
UniPathwayiUPA00057; UER00098.

Protein family/group databases

MoonProtiP17256.

Names & Taxonomyi

Protein namesi
Recommended name:
Mevalonate kinase (EC:2.7.1.36)
Short name:
MK
Gene namesi
Name:Mvk
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621295. Mvk.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: RGD
  • peroxisome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Peroxisome

Pathology & Biotechi

Involvement in diseasei

Mutation in the mevalonate kinase gene causes mevalonicaciduria.

Chemistry

ChEMBLiCHEMBL4274.
GuidetoPHARMACOLOGYi640.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 395395Mevalonate kinasePRO_0000156659Add
BLAST

Proteomic databases

PRIDEiP17256.

PTM databases

iPTMnetiP17256.
PhosphoSiteiP17256.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi249600. 5 interactions.

Chemistry

BindingDBiP17256.

Structurei

Secondary structure

1
395
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi6 – 1712Combined sources
Helixi21 – 244Combined sources
Beta strandi28 – 4316Combined sources
Beta strandi45 – 539Combined sources
Turni54 – 574Combined sources
Beta strandi58 – 636Combined sources
Helixi64 – 685Combined sources
Helixi90 – 956Combined sources
Helixi106 – 12015Combined sources
Beta strandi123 – 1253Combined sources
Beta strandi129 – 1379Combined sources
Beta strandi141 – 1433Combined sources
Helixi145 – 16016Combined sources
Helixi167 – 1704Combined sources
Beta strandi173 – 1753Combined sources
Helixi179 – 19719Combined sources
Helixi203 – 2108Combined sources
Beta strandi212 – 2198Combined sources
Beta strandi221 – 2233Combined sources
Beta strandi230 – 2367Combined sources
Helixi243 – 25614Combined sources
Helixi258 – 28225Combined sources
Helixi288 – 30821Combined sources
Helixi313 – 32412Combined sources
Beta strandi328 – 3314Combined sources
Beta strandi336 – 3449Combined sources
Helixi350 – 36213Combined sources
Beta strandi366 – 3738Combined sources
Beta strandi377 – 3804Combined sources
Turni382 – 3843Combined sources
Helixi387 – 3937Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KVKX-ray2.40A1-395[»]
2R42X-ray2.40A1-395[»]
ProteinModelPortaliP17256.
SMRiP17256. Positions 1-395.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17256.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

HOVERGENiHBG000402.
InParanoidiP17256.
KOiK00869.
PhylomeDBiP17256.

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.
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]
PANTHERiPTHR10457. PTHR10457. 1 hit.
PTHR10457:SF4. PTHR10457:SF4. 1 hit.
PfamiPF08544. GHMP_kinases_C. 1 hit.
PF00288. GHMP_kinases_N. 1 hit.
[Graphical view]
PRINTSiPR00959. MEVGALKINASE.
SUPFAMiSSF54211. SSF54211. 1 hit.
SSF55060. SSF55060. 1 hit.
TIGRFAMsiTIGR00549. mevalon_kin. 1 hit.
PROSITEiPS00627. GHMP_KINASES_ATP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P17256-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLSEVLLVSA PGKVILHGEH AVVHGKVALA VALNLRTFLV LRPQSNGKVS
60 70 80 90 100
LNLPNVGIKQ VWDVATLQLL DTGFLEQGDV PAPTLEQLEK LKKVAGLPRD
110 120 130 140 150
CVGNEGLSLL AFLYLYLAIC RKQRTLPSLD IMVWSELPPG AGLGSSAAYS
160 170 180 190 200
VCVAAALLTA CEEVTNPLKD RGSIGSWPEE DLKSINKWAY EGERVIHGNP
210 220 230 240 250
SGVDNSVSTW GGALRYQQGK MSSLKRLPAL QILLTNTKVP RSTKALVAGV
260 270 280 290 300
RSRLIKFPEI MAPLLTSIDA ISLECERVLG EMAAAPVPEQ YLVLEELMDM
310 320 330 340 350
NQHHLNALGV GHASLDQLCQ VTAAHGLHSK LTGAGGGGCG ITLLKPGLER
360 370 380 390
AKVEAAKQAL TGCGFDCWET SIGAPGVSMH SATSIEDPVR QALGL
Length:395
Mass (Da):41,988
Last modified:August 1, 1990 - v1
Checksum:i803D1F44E3C525FC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M29472 mRNA. Translation: AAA41588.1.
PIRiA35629.
RefSeqiNP_112325.1. NM_031063.1.
UniGeneiRn.6995.

Genome annotation databases

GeneIDi81727.
KEGGirno:81727.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M29472 mRNA. Translation: AAA41588.1.
PIRiA35629.
RefSeqiNP_112325.1. NM_031063.1.
UniGeneiRn.6995.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KVKX-ray2.40A1-395[»]
2R42X-ray2.40A1-395[»]
ProteinModelPortaliP17256.
SMRiP17256. Positions 1-395.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249600. 5 interactions.

Chemistry

BindingDBiP17256.
ChEMBLiCHEMBL4274.
GuidetoPHARMACOLOGYi640.

Protein family/group databases

MoonProtiP17256.

PTM databases

iPTMnetiP17256.
PhosphoSiteiP17256.

Proteomic databases

PRIDEiP17256.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi81727.
KEGGirno:81727.

Organism-specific databases

CTDi4598.
RGDi621295. Mvk.

Phylogenomic databases

HOVERGENiHBG000402.
InParanoidiP17256.
KOiK00869.
PhylomeDBiP17256.

Enzyme and pathway databases

UniPathwayiUPA00057; UER00098.
BRENDAi2.7.1.36. 5301.
SABIO-RKP17256.

Miscellaneous databases

EvolutionaryTraceiP17256.
NextBioi615384.
PROiP17256.

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.
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]
PANTHERiPTHR10457. PTHR10457. 1 hit.
PTHR10457:SF4. PTHR10457:SF4. 1 hit.
PfamiPF08544. GHMP_kinases_C. 1 hit.
PF00288. GHMP_kinases_N. 1 hit.
[Graphical view]
PRINTSiPR00959. MEVGALKINASE.
SUPFAMiSSF54211. SSF54211. 1 hit.
SSF55060. SSF55060. 1 hit.
TIGRFAMsiTIGR00549. mevalon_kin. 1 hit.
PROSITEiPS00627. GHMP_KINASES_ATP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Molecular cloning of mevalonate kinase and regulation of its mRNA levels in rat liver."
    Tanaka R.D., Lee L.Y., Schafer B.L., Kratunis V.J., Mohler W.A., Robinson G.W., Mosley S.T.
    Proc. Natl. Acad. Sci. U.S.A. 87:2872-2876(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-20.
    Strain: Sprague-Dawley.
    Tissue: Liver.
  2. Cited for: SUBCELLULAR LOCATION.
  3. "Mevalonate kinase is localized in rat liver peroxisomes."
    Stamellos K.D., Shackelford J.E., Tanaka R.D., Krisans S.K.
    J. Biol. Chem. 267:5560-5568(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  4. "The structure of a binary complex between a mammalian mevalonate kinase and ATP: insights into the reaction mechanism and human inherited disease."
    Fu Z., Wang M., Potter D., Miziorko H.M., Kim J.-J.
    J. Biol. Chem. 277:18134-18142(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH ATP, SUBUNIT.

Entry informationi

Entry nameiKIME_RAT
AccessioniPrimary (citable) accession number: P17256
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: February 17, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The authors of PubMed:14730012 identify two forms of Mvk in rat liver, one form localizes to the cytosol and the other form to the peroxisome, whereas according to the authors of PubMed:14730012 the protein is found only in the cytoplasm with no evidence for its peroxisomal localization.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.