PMVK_MOUSE
ID PMVK_MOUSE Reviewed; 192 AA.
AC Q9D1G2; Q8R021; Q9D6K3;
DT 27-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Phosphomevalonate kinase;
DE Short=PMKase;
DE EC=2.7.4.2 {ECO:0000250|UniProtKB:Q15126};
GN Name=Pmvk;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC 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, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC 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 reversible ATP-dependent phosphorylation of
CC mevalonate 5-phosphate to produce mevalonate diphosphate and ADP, a key
CC step in the mevalonic acid mediated biosynthesis of isopentenyl
CC diphosphate and other polyisoprenoid metabolites.
CC {ECO:0000250|UniProtKB:Q15126}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate +
CC ADP; Xref=Rhea:RHEA:16341, ChEBI:CHEBI:30616, ChEBI:CHEBI:57557,
CC ChEBI:CHEBI:58146, ChEBI:CHEBI:456216; EC=2.7.4.2;
CC Evidence={ECO:0000250|UniProtKB:Q15126};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16342;
CC Evidence={ECO:0000250|UniProtKB:Q15126};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16343;
CC Evidence={ECO:0000250|UniProtKB:Q15126};
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC step 2/3. {ECO:0000305}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q15126}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q15126}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9D1G2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9D1G2-2; Sequence=VSP_007650, VSP_007651;
CC Name=3;
CC IsoId=Q9D1G2-3; Sequence=VSP_007649;
CC -!- CAUTION: Was originally thought to be located in the peroxisome.
CC However, was later shown to be cytosolic.
CC {ECO:0000250|UniProtKB:Q15126}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK003607; BAB22886.1; -; mRNA.
DR EMBL; AK013477; BAB28875.1; -; mRNA.
DR EMBL; BC028659; AAH28659.1; -; mRNA.
DR CCDS; CCDS17511.1; -. [Q9D1G2-1]
DR CCDS; CCDS71270.1; -. [Q9D1G2-2]
DR CCDS; CCDS79953.1; -. [Q9D1G2-3]
DR RefSeq; NP_001297569.1; NM_001310640.1. [Q9D1G2-3]
DR RefSeq; NP_081060.2; NM_026784.3. [Q9D1G2-1]
DR RefSeq; NP_081624.1; NM_027348.1. [Q9D1G2-2]
DR AlphaFoldDB; Q9D1G2; -.
DR SMR; Q9D1G2; -.
DR BioGRID; 212946; 2.
DR STRING; 10090.ENSMUSP00000029564; -.
DR iPTMnet; Q9D1G2; -.
DR PhosphoSitePlus; Q9D1G2; -.
DR EPD; Q9D1G2; -.
DR MaxQB; Q9D1G2; -.
DR PaxDb; Q9D1G2; -.
DR PeptideAtlas; Q9D1G2; -.
DR PRIDE; Q9D1G2; -.
DR ProteomicsDB; 289461; -. [Q9D1G2-1]
DR ProteomicsDB; 289462; -. [Q9D1G2-2]
DR ProteomicsDB; 289463; -. [Q9D1G2-3]
DR Antibodypedia; 34158; 246 antibodies from 28 providers.
DR DNASU; 68603; -.
DR Ensembl; ENSMUST00000029564; ENSMUSP00000029564; ENSMUSG00000027952. [Q9D1G2-1]
DR Ensembl; ENSMUST00000184515; ENSMUSP00000139116; ENSMUSG00000027952. [Q9D1G2-2]
DR Ensembl; ENSMUST00000198440; ENSMUSP00000143154; ENSMUSG00000027952. [Q9D1G2-3]
DR GeneID; 68603; -.
DR KEGG; mmu:68603; -.
DR UCSC; uc008pzs.2; mouse. [Q9D1G2-1]
DR UCSC; uc012csn.1; mouse. [Q9D1G2-2]
DR CTD; 10654; -.
DR MGI; MGI:1915853; Pmvk.
DR VEuPathDB; HostDB:ENSMUSG00000027952; -.
DR eggNOG; ENOG502QYPQ; Eukaryota.
DR GeneTree; ENSGT00390000014801; -.
DR HOGENOM; CLU_092097_0_0_1; -.
DR InParanoid; Q9D1G2; -.
DR OMA; YGFFCRA; -.
DR PhylomeDB; Q9D1G2; -.
DR TreeFam; TF312935; -.
DR Reactome; R-MMU-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00057; UER00099.
DR BioGRID-ORCS; 68603; 26 hits in 72 CRISPR screens.
DR ChiTaRS; Pmvk; mouse.
DR PRO; PR:Q9D1G2; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9D1G2; protein.
DR Bgee; ENSMUSG00000027952; Expressed in bone fossa and 253 other tissues.
DR ExpressionAtlas; Q9D1G2; baseline and differential.
DR Genevisible; Q9D1G2; MM.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0004631; F:phosphomevalonate kinase activity; IDA: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:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0070723; P:response to cholesterol; IEA:Ensembl.
DR GO; GO:0016126; P:sterol biosynthetic process; ISO:MGI.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005919; Pmev_kin_anim.
DR PANTHER; PTHR13101; PTHR13101; 1.
DR Pfam; PF04275; P-mevalo_kinase; 1.
DR PIRSF; PIRSF036639; PMK_anim; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR01223; Pmev_kin_anim; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cholesterol biosynthesis;
KW Cholesterol metabolism; Cytoplasm; Kinase; Lipid biosynthesis;
KW Lipid metabolism; Nucleotide-binding; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transferase.
FT CHAIN 1..192
FT /note="Phosphomevalonate kinase"
FT /id="PRO_0000058473"
FT BINDING 17..23
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15126"
FT BINDING 141
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15126"
FT BINDING 170
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15126"
FT BINDING 171
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15126"
FT BINDING 180
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15126"
FT VAR_SEQ 1..75
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007649"
FT VAR_SEQ 1..21
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_007650"
FT VAR_SEQ 22..31
FT /note="KDFVTERLKS -> MAGIYGIFYA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_007651"
FT CONFLICT 147
FT /note="P -> L (in Ref. 1; BAB22886)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 192 AA; 21916 MW; 153155EC22693857 CRC64;
MAPLGASPRL VLLFSGKRKS GKDFVTERLK SRLGGNICAL LRLSGPLKEE YAREHGLDFQ
RLLDASTYKE TYRRDMICWG EQKRQADPGF FCRKIVEGVS QPIWLVSDTR RTSDIQWFQE
AYGAVIQTVR VVASEQSRQQ RGWVFTPGVD DAESECGLDN FGNFDWVIEN HGDEQCLEDQ
LEHLLGFIQA KL
