KIME_MOUSE
ID KIME_MOUSE Reviewed; 395 AA.
AC Q9R008;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Mevalonate kinase {ECO:0000305};
DE Short=MK;
DE EC=2.7.1.36 {ECO:0000250|UniProtKB:Q03426};
GN Name=Mvk {ECO:0000312|MGI:MGI:107624};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10401001; DOI=10.1093/hmg/8.8.1523;
RA Houten S.M., Romeijn G.J., Koster J., Gray R.G.F., Darbyshire P.,
RA Smit G.P.A., de Klerk J.B.C., Duran R., Gibson K.M., Wanders R.J.A.,
RA Waterham H.R.;
RT "Identification and characterization of three novel missense mutations in
RT mevalonate kinase cDNA causing mevalonic aciduria, a disorder of isoprene
RT biosynthesis.";
RL Hum. Mol. Genet. 8:1523-1528(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the phosphorylation of mevalonate to mevalonate 5-
CC phosphate, a key step in isoprenoid and cholesterol biosynthesis.
CC {ECO:0000250|UniProtKB:Q03426}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+);
CC Xref=Rhea:RHEA:17065, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:36464, ChEBI:CHEBI:58146, ChEBI:CHEBI:456216;
CC EC=2.7.1.36; Evidence={ECO:0000250|UniProtKB:Q03426};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P17256};
CC -!- ACTIVITY REGULATION: Farnesyl pyrophosphate and geranyl pyrophosphate
CC inhibit mevalonate kinase activity by binding competitively at the ATP-
CC binding sites. {ECO:0000250|UniProtKB:Q03426}.
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC step 1/3.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q03426}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P17256}.
CC Peroxisome {ECO:0000250|UniProtKB:P17256}.
CC -!- SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase
CC subfamily. {ECO:0000305}.
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DR EMBL; AF137598; AAF00700.1; -; mRNA.
DR EMBL; BC005606; AAH05606.1; -; mRNA.
DR CCDS; CCDS19566.1; -.
DR RefSeq; NP_076045.1; NM_023556.3.
DR RefSeq; XP_006530248.1; XM_006530185.3.
DR AlphaFoldDB; Q9R008; -.
DR SMR; Q9R008; -.
DR BioGRID; 201627; 1.
DR STRING; 10090.ENSMUSP00000036971; -.
DR PhosphoSitePlus; Q9R008; -.
DR EPD; Q9R008; -.
DR jPOST; Q9R008; -.
DR MaxQB; Q9R008; -.
DR PaxDb; Q9R008; -.
DR PeptideAtlas; Q9R008; -.
DR PRIDE; Q9R008; -.
DR ProteomicsDB; 263609; -.
DR Antibodypedia; 2047; 398 antibodies from 32 providers.
DR DNASU; 17855; -.
DR Ensembl; ENSMUST00000043760; ENSMUSP00000036971; ENSMUSG00000041939.
DR GeneID; 17855; -.
DR KEGG; mmu:17855; -.
DR UCSC; uc008yzq.1; mouse.
DR CTD; 4598; -.
DR MGI; MGI:107624; Mvk.
DR VEuPathDB; HostDB:ENSMUSG00000041939; -.
DR eggNOG; KOG1511; Eukaryota.
DR GeneTree; ENSGT00950000183187; -.
DR HOGENOM; CLU_017814_0_1_1; -.
DR InParanoid; Q9R008; -.
DR OMA; NTVCTYG; -.
DR PhylomeDB; Q9R008; -.
DR TreeFam; TF313775; -.
DR BRENDA; 2.7.1.36; 3474.
DR Reactome; R-MMU-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00057; UER00098.
DR BioGRID-ORCS; 17855; 28 hits in 77 CRISPR screens.
DR ChiTaRS; Mvk; mouse.
DR PRO; PR:Q9R008; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9R008; protein.
DR Bgee; ENSMUSG00000041939; Expressed in skin of snout and 261 other tissues.
DR ExpressionAtlas; Q9R008; baseline and differential.
DR Genevisible; Q9R008; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0004496; F:mevalonate kinase activity; IDA:MGI.
DR GO; GO:0003729; F:mRNA binding; ISO:MGI.
DR GO; GO:1990825; F:sequence-specific mRNA binding; ISO:MGI.
DR GO; GO:0006695; P:cholesterol biosynthetic process; ISO:MGI.
DR GO; GO:0019287; P:isopentenyl diphosphate biosynthetic process, mevalonate pathway; ISO:MGI.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; ISO:MGI.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:MGI.
DR GO; GO:0017148; P:negative regulation of translation; ISO:MGI.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.70.890; -; 1.
DR InterPro; IPR013750; GHMP_kinase_C_dom.
DR InterPro; IPR036554; GHMP_kinase_C_sf.
DR InterPro; IPR006204; GHMP_kinase_N_dom.
DR InterPro; IPR006203; GHMP_knse_ATP-bd_CS.
DR InterPro; IPR006205; Mev_gal_kin.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR PANTHER; PTHR43290; PTHR43290; 1.
DR Pfam; PF08544; GHMP_kinases_C; 1.
DR Pfam; PF00288; GHMP_kinases_N; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55060; SSF55060; 1.
DR TIGRFAMs; TIGR00549; mevalon_kin; 1.
DR PROSITE; PS00627; GHMP_KINASES_ATP; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cholesterol biosynthesis; Cholesterol metabolism; Cytoplasm;
KW Kinase; Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding;
KW Nucleotide-binding; Peroxisome; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase.
FT CHAIN 1..395
FT /note="Mevalonate kinase"
FT /id="PRO_0000156658"
FT ACT_SITE 146
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q03426"
FT ACT_SITE 204
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q03426"
FT BINDING 13
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 55
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 104
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 135
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 140..146
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 146
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 193
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P17256"
SQ SEQUENCE 395 AA; 41877 MW; 953DB1C89403A3F8 CRC64;
MLSEALLVSA PGKVILHGEH AVVHGKVALA AALNLRTFLL LRPQSNGKVS VNLPNIGIKQ
VWDVGMLQRL DTSFLEQGDV SVPTLEQLEK LKKMGDLPRD RAGNEGMALL AFLYLYLAIC
RKQRTLPSLD MVVWSELPPG AGLGSSAAYS VCLAAALLTA CEEVSNPLKD GVSVSRWPEE
DLKSINKWAF EGERVIHGNP SGVDNAVSTW GGALRFQQGT MSSLKSLPSL QILLTNTKVP
RSTKALVAAV RSRLTKFPEI VAPLLTSIDA ISLECERVLG EMVAAPVPEQ YLVLEELIDM
NQHHLNALGV GHNSLDQLCQ VTAAHGLHSK LTGAGGGGCG ITLLKPGLEQ ATVEAAKQAL
TSCGFDCWET SIGAPGVSTH SAAAVGDPVR QALGL
