ERG8_YEAST
ID ERG8_YEAST Reviewed; 451 AA.
AC P24521; D6W045;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Phosphomevalonate kinase {ECO:0000303|PubMed:1846667};
DE EC=2.7.4.2 {ECO:0000269|PubMed:1846667};
GN Name=ERG8 {ECO:0000303|PubMed:1846667}; OrderedLocusNames=YMR220W;
GN ORFNames=YM9959.02;
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] OF 1-424, FUNCTION, CATALYTIC ACTIVITY,
RP AND PATHWAY.
RX PubMed=1846667; DOI=10.1128/mcb.11.2.620-631.1991;
RA Tsay Y.H., Robinson G.W.;
RT "Cloning and characterization of ERG8, an essential gene of Saccharomyces
RT cerevisiae that encodes phosphomevalonate kinase.";
RL Mol. Cell. Biol. 11:620-631(1991).
RN [2]
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 [3]
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 [4]
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 [5]
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: Phosphomevalonate kinase; part of the second module of
CC ergosterol biosynthesis pathway that includes the middle steps of the
CC pathway (PubMed:1846667). ERG8 converts 5-phosphomevalonate to 5-
CC diphosphomevalonate (PubMed:1846667). The second module is carried out
CC in the vacuole and involves the formation of farnesyl diphosphate,
CC which is also an important intermediate in the biosynthesis of
CC ubiquinone, dolichol, heme and prenylated proteins. Activity by the
CC mevalonate kinase ERG12 first converts mevalonate into 5-
CC phosphomevalonate. 5-phosphomevalonate is then further converted to 5-
CC diphosphomevalonate by the phosphomevalonate kinase ERG8. The
CC diphosphomevalonate decarboxylase MVD1/ERG19 then produces isopentenyl
CC diphosphate. The isopentenyl-diphosphate delta-isomerase IDI1 then
CC catalyzes the 1,3-allylic rearrangement of the homoallylic substrate
CC isopentenyl (IPP) to its highly electrophilic allylic isomer,
CC dimethylallyl diphosphate (DMAPP). Finally the farnesyl diphosphate
CC synthase ERG20 catalyzes the sequential condensation of isopentenyl
CC pyrophosphate with dimethylallyl pyrophosphate, and then with the
CC resultant geranylpyrophosphate to the ultimate product farnesyl
CC pyrophosphate (PubMed:32679672). {ECO:0000269|PubMed:1846667,
CC ECO:0000303|PubMed:32679672}.
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:0000269|PubMed:1846667};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16342;
CC Evidence={ECO:0000269|PubMed:1846667};
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC step 2/3. {ECO:0000269|PubMed:1846667}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:1846667}.
CC -!- MISCELLANEOUS: Present with 79 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; M63648; AAA34596.1; -; Genomic_DNA.
DR EMBL; Z49939; CAA90191.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA10119.1; -; Genomic_DNA.
DR PIR; S57588; S57588.
DR RefSeq; NP_013947.1; NM_001182727.1.
DR AlphaFoldDB; P24521; -.
DR SMR; P24521; -.
DR BioGRID; 35398; 155.
DR STRING; 4932.YMR220W; -.
DR MaxQB; P24521; -.
DR PaxDb; P24521; -.
DR PRIDE; P24521; -.
DR TopDownProteomics; P24521; -.
DR EnsemblFungi; YMR220W_mRNA; YMR220W; YMR220W.
DR GeneID; 855260; -.
DR KEGG; sce:YMR220W; -.
DR SGD; S000004833; ERG8.
DR VEuPathDB; FungiDB:YMR220W; -.
DR eggNOG; KOG4519; Eukaryota.
DR HOGENOM; CLU_022059_1_0_1; -.
DR InParanoid; P24521; -.
DR OMA; LVIHRTM; -.
DR BioCyc; MetaCyc:YMR220W-MON; -.
DR BioCyc; YEAST:YMR220W-MON; -.
DR BRENDA; 2.7.4.2; 984.
DR UniPathway; UPA00057; UER00099.
DR PRO; PR:P24521; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; P24521; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0005777; C:peroxisome; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004631; F:phosphomevalonate kinase activity; IMP: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:0031388; P:organic acid phosphorylation; IMP:SGD.
DR Gene3D; 3.30.230.10; -; 1.
DR InterPro; IPR016005; Erg8.
DR InterPro; IPR013750; GHMP_kinase_C_dom.
DR InterPro; IPR006204; GHMP_kinase_N_dom.
DR InterPro; IPR006203; GHMP_knse_ATP-bd_CS.
DR InterPro; IPR035102; Phosphomevalonate_kinase.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR PANTHER; PTHR31814; PTHR31814; 1.
DR Pfam; PF08544; GHMP_kinases_C; 1.
DR Pfam; PF00288; GHMP_kinases_N; 1.
DR PIRSF; PIRSF017288; PMK_GHMP_euk; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR TIGRFAMs; TIGR01219; Pmev_kin_ERG8; 1.
DR PROSITE; PS00627; GHMP_KINASES_ATP; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Isoprene biosynthesis; Kinase; Lipid biosynthesis;
KW Lipid metabolism; Nucleotide-binding; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transferase.
FT CHAIN 1..451
FT /note="Phosphomevalonate kinase"
FT /id="PRO_0000156671"
FT BINDING 150..160
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT CONFLICT 213
FT /note="A -> R (in Ref. 1; AAA34596)"
FT /evidence="ECO:0000305"
FT CONFLICT 418..423
FT /note="TANDKR -> PLMTKD (in Ref. 1; AAA34596)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 451 AA; 50455 MW; DB2B6C862153683C CRC64;
MSELRAFSAP GKALLAGGYL VLDTKYEAFV VGLSARMHAV AHPYGSLQGS DKFEVRVKSK
QFKDGEWLYH ISPKSGFIPV SIGGSKNPFI EKVIANVFSY FKPNMDDYCN RNLFVIDIFS
DDAYHSQEDS VTEHRGNRRL SFHSHRIEEV PKTGLGSSAG LVTVLTTALA SFFVSDLENN
VDKYREVIHN LAQVAHCQAQ GKIGSGFDVA AAAYGSIRYR RFPPALISNL PDIGSATYGS
KLAHLVDEED WNITIKSNHL PSGLTLWMGD IKNGSETVKL VQKVKNWYDS HMPESLKIYT
ELDHANSRFM DGLSKLDRLH ETHDDYSDQI FESLERNDCT CQKYPEITEV RDAVATIRRS
FRKITKESGA DIEPPVQTSL LDDCQTLKGV LTCLIPGAGG YDAIAVITKQ DVDLRAQTAN
DKRFSKVQWL DVTQADWGVR KEKDPETYLD K
