ERG12_YEAST
ID ERG12_YEAST Reviewed; 443 AA.
AC P07277; D6W033;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1988, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Mevalonate kinase {ECO:0000303|PubMed:1645230};
DE Short=MK {ECO:0000303|PubMed:1645230};
DE Short=MvK {ECO:0000303|PubMed:1645230};
DE EC=2.7.1.36 {ECO:0000269|PubMed:1645230};
DE AltName: Full=Ergosterol biosynthesis protein 12 {ECO:0000303|PubMed:1645230};
DE AltName: Full=Regulation of autonomous replication protein 1 {ECO:0000303|PubMed:3323847};
GN Name=ERG12 {ECO:0000303|PubMed:1645230};
GN Synonyms=RAR1 {ECO:0000303|PubMed:3323847}; OrderedLocusNames=YMR208W;
GN ORFNames=YM8261.02;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3323847; DOI=10.1007/bf00327205;
RA Kearsey S.E., Edwards J.;
RT "Mutations that increase the mitotic stability of minichromosomes in yeast:
RT characterization of RAR1.";
RL Mol. Gen. Genet. 210:509-517(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND PATHWAY.
RX PubMed=1645230; DOI=10.1007/bf00362081;
RA Oulmouden A., Karst F.;
RT "Nucleotide sequence of the ERG12 gene of Saccharomyces cerevisiae encoding
RT mevalonate kinase.";
RL Curr. Genet. 19:9-14(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169872;
RA Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL Nature 387:90-93(1997).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-246.
RC STRAIN=SP1;
RA Saito A., Kazuta Y., Kondo H., Tanabe T.;
RL Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [7]
RP REVIEW ON ERGOSTEROL BIOSYNTHESIS.
RX PubMed=32679672; DOI=10.3390/genes11070795;
RA Jorda T., Puig S.;
RT "Regulation of ergosterol biosynthesis in Saccharomyces cerevisiae.";
RL Genes (Basel) 11:0-0(2020).
CC -!- FUNCTION: Mevalonate kinase; part of the second module of ergosterol
CC biosynthesis pathway that includes the middle steps of the pathway
CC (PubMed:1645230). ERG12 converts mevalonate into 5-phosphomevalonate
CC (PubMed:1645230). The second module is carried out in the vacuole and
CC involves the formation of farnesyl diphosphate, which is also an
CC important intermediate in the biosynthesis of ubiquinone, dolichol,
CC heme and prenylated proteins. Activity by the mevalonate kinase ERG12
CC first converts mevalonate into 5-phosphomevalonate. 5-phosphomevalonate
CC is then further converted to 5-diphosphomevalonate by the
CC phosphomevalonate kinase ERG8. The diphosphomevalonate decarboxylase
CC MVD1/ERG19 then produces isopentenyl diphosphate. The isopentenyl-
CC diphosphate delta-isomerase IDI1 then catalyzes the 1,3-allylic
CC rearrangement of the homoallylic substrate isopentenyl (IPP) to its
CC highly electrophilic allylic isomer, dimethylallyl diphosphate (DMAPP).
CC Finally the farnesyl diphosphate synthase ERG20 catalyzes the
CC sequential condensation of isopentenyl pyrophosphate with dimethylallyl
CC pyrophosphate, and then with the resultant geranylpyrophosphate to the
CC ultimate product farnesyl pyrophosphate (PubMed:32679672).
CC {ECO:0000269|PubMed:1645230, ECO:0000303|PubMed:32679672}.
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:0000269|PubMed:1645230};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17066;
CC Evidence={ECO:0000269|PubMed:1645230};
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 by binding competitively at the ATP-binding
CC site. {ECO:0000269|PubMed:1645230}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.13 mM for mevalonate {ECO:0000269|PubMed:1645230};
CC Vmax=27 nmol/min/mg enzyme {ECO:0000269|PubMed:1645230};
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC step 1/3. {ECO:0000269|PubMed:1645230}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P17256}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:1645230}.
CC -!- MISCELLANEOUS: Present with 3300 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase
CC subfamily. {ECO:0000305}.
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DR EMBL; X06114; CAA29487.1; -; Genomic_DNA.
DR EMBL; X55875; CAA39359.1; -; Genomic_DNA.
DR EMBL; Z49809; CAA89923.1; -; Genomic_DNA.
DR EMBL; D78165; BAA24409.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA10107.1; -; Genomic_DNA.
DR PIR; S05875; BVBYR1.
DR RefSeq; NP_013935.1; NM_001182715.1.
DR AlphaFoldDB; P07277; -.
DR SMR; P07277; -.
DR BioGRID; 35386; 97.
DR IntAct; P07277; 3.
DR STRING; 4932.YMR208W; -.
DR iPTMnet; P07277; -.
DR MaxQB; P07277; -.
DR PaxDb; P07277; -.
DR PRIDE; P07277; -.
DR EnsemblFungi; YMR208W_mRNA; YMR208W; YMR208W.
DR GeneID; 855248; -.
DR KEGG; sce:YMR208W; -.
DR SGD; S000004821; ERG12.
DR VEuPathDB; FungiDB:YMR208W; -.
DR eggNOG; KOG1511; Eukaryota.
DR GeneTree; ENSGT00950000183187; -.
DR HOGENOM; CLU_017814_0_1_1; -.
DR InParanoid; P07277; -.
DR OMA; NTVCTYG; -.
DR BioCyc; MetaCyc:YMR208W-MON; -.
DR BioCyc; YEAST:YMR208W-MON; -.
DR Reactome; R-SCE-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00057; UER00098.
DR ChiTaRS; ERG12; yeast.
DR PRO; PR:P07277; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; P07277; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005829; C:cytosol; HDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0004496; F:mevalonate kinase activity; IDA:SGD.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IMP:SGD.
DR GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IMP:SGD.
DR GO; GO:0019287; P:isopentenyl diphosphate biosynthetic process, mevalonate pathway; IMP:SGD.
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; Cytoplasm; Kinase; Lipid biosynthesis; Lipid metabolism;
KW Magnesium; Metal-binding; Nucleotide-binding; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transferase.
FT CHAIN 1..443
FT /note="Mevalonate kinase"
FT /id="PRO_0000156662"
FT ACT_SITE 202
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q03426"
FT BINDING 12
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 138
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 143..149
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 149
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 191
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P17256"
SQ SEQUENCE 443 AA; 48460 MW; 8B24052A72C97280 CRC64;
MSLPFLTSAP GKVIIFGEHS AVYNKPAVAA SVSALRTYLL ISESSAPDTI ELDFPDISFN
HKWSINDFNA ITEDQVNSQK LAKAQQATDG LSQELVSLLD PLLAQLSESF HYHAAFCFLY
MFVCLCPHAK NIKFSLKSTL PIGAGLGSSA SISVSLALAM AYLGGLIGSN DLEKLSENDK
HIVNQWAFIG EKCIHGTPSG IDNAVATYGN ALLFEKDSHN GTINTNNFKF LDDFPAIPMI
LTYTRIPRST KDLVARVRVL VTEKFPEVMK PILDAMGECA LQGLEIMTKL SKCKGTDDEA
VETNNELYEQ LLELIRINHG LLVSIGVSHP GLELIKNLSD DLRIGSTKLT GAGGGGCSLT
LLRRDITQEQ IDSFKKKLQD DFSYETFETD LGGTGCCLLS AKNLNKDLKI KSLVFQLFEN
KTTTKQQIDD LLLPGNTNLP WTS
