ID   ERG8_SCHPO              Reviewed;         426 AA.
AC   Q9UT88;
DT   13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   03-AUG-2022, entry version 116.
DE   RecName: Full=Phosphomevalonate kinase {ECO:0000250|UniProtKB:P24521};
DE            EC=2.7.4.2 {ECO:0000250|UniProtKB:P24521};
GN   Name=erg8; ORFNames=SPAC343.01c;
OS   Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC   Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC   Schizosaccharomyces.
OX   NCBI_TaxID=284812;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=972 / ATCC 24843;
RX   PubMed=11859360; DOI=10.1038/nature724;
RA   Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA   Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA   Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA   Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA   Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA   Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA   Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA   Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA   O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA   Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA   Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA   Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA   Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA   Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA   Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA   Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA   Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA   Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA   Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA   Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA   del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA   Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA   Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA   Nurse P.;
RT   "The genome sequence of Schizosaccharomyces pombe.";
RL   Nature 415:871-880(2002).
RN   [2]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=16823372; DOI=10.1038/nbt1222;
RA   Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA   Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA   Yoshida M.;
RT   "ORFeome cloning and global analysis of protein localization in the fission
RT   yeast Schizosaccharomyces pombe.";
RL   Nat. Biotechnol. 24:841-847(2006).
CC   -!- FUNCTION: Phosphomevalonate kinase; part of the second module of
CC       ergosterol biosynthesis pathway that includes the middle steps of the
CC       pathway (By similarity). Erg8 converts 5-phosphomevalonate to 5-
CC       diphosphomevalonate (By similarity). 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 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 fps1 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 (Probable). {ECO:0000250|UniProtKB:P24521, ECO:0000305}.
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:P24521};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16342;
CC         Evidence={ECO:0000250|UniProtKB:P24521};
CC   -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC       via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC       step 2/3. {ECO:0000250|UniProtKB:P24521}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}.
CC       Mitochondrion {ECO:0000269|PubMed:16823372}. Nucleus
CC       {ECO:0000269|PubMed:16823372}.
CC   -!- SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase
CC       subfamily. {ECO:0000305}.
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DR   EMBL; CU329670; CAB52264.1; -; Genomic_DNA.
DR   PIR; T38650; T38650.
DR   RefSeq; NP_593421.3; NM_001018854.3.
DR   AlphaFoldDB; Q9UT88; -.
DR   SMR; Q9UT88; -.
DR   IntAct; Q9UT88; 3.
DR   STRING; 4896.SPAC343.01c.1; -.
DR   MaxQB; Q9UT88; -.
DR   PaxDb; Q9UT88; -.
DR   EnsemblFungi; SPAC343.01c.1; SPAC343.01c.1:pep; SPAC343.01c.
DR   GeneID; 2543184; -.
DR   KEGG; spo:SPAC343.01c; -.
DR   PomBase; SPAC343.01c; erg8.
DR   VEuPathDB; FungiDB:SPAC343.01c; -.
DR   eggNOG; KOG4519; Eukaryota.
DR   HOGENOM; CLU_022059_1_0_1; -.
DR   InParanoid; Q9UT88; -.
DR   OMA; LVIHRTM; -.
DR   PhylomeDB; Q9UT88; -.
DR   UniPathway; UPA00057; UER00099.
DR   PRO; PR:Q9UT88; -.
DR   Proteomes; UP000002485; Chromosome I.
DR   GO; GO:0005829; C:cytosol; HDA:PomBase.
DR   GO; GO:0005739; C:mitochondrion; HDA:PomBase.
DR   GO; GO:0005634; C:nucleus; HDA:PomBase.
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; ISS:PomBase.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; ISS:PomBase.
DR   GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IBA:GO_Central.
DR   GO; GO:0019287; P:isopentenyl diphosphate biosynthetic process, mevalonate pathway; IBA:GO_Central.
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; IPR016005; Erg8.
DR   InterPro; IPR013750; GHMP_kinase_C_dom.
DR   InterPro; IPR036554; GHMP_kinase_C_sf.
DR   InterPro; IPR006204; GHMP_kinase_N_dom.
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.
PE   3: Inferred from homology;
KW   ATP-binding; Cytoplasm; Isoprene biosynthesis; Kinase; Lipid biosynthesis;
KW   Lipid metabolism; Mitochondrion; Nucleotide-binding; Nucleus;
KW   Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW   Sterol biosynthesis; Sterol metabolism; Transferase.
FT   CHAIN           1..426
FT                   /note="Phosphomevalonate kinase"
FT                   /id="PRO_0000310369"
FT   BINDING         151..161
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   426 AA;  47322 MW;  25635B99E7FAAD64 CRC64;
     MKVTCSAPGK VLIAGGYIVL DPQYSGLVIG LTAKGYASTT TLDDKCGTVR VKSPQFINAE
     WLYNIDWTVS PIRVHQIYEN CELEKNPNPF VQLALFYVIN YFFSTGRQPL CWQDLQVTLQ
     VDNAYYHQPQ LKPDQTSYPK FNFLNCTLGQ VHKTGLGSSA AMITSLIGSL FLSLRRLTDD
     TGDKSLKIDD STKVIVHNLA QIAHCSAQGK VGSGFDVGAA TWGSCIYRRF DPKLIEQLLV
     PYDEQIKNIN FSTELRKIVS KKWSDVVPFQ LPATYCLLMG DVAGGSSTPG MVKKVQQWQK
     ENPEESKNCF DDLYSRVLSI KNCFLSSESL DSELQSQFRS IRRILQRITV EAKVDIEPLK
     QTNILDNIEQ LPGVIGVGVP GAGGFDAQFC LAINHTEIIE NVIKTWKDDG VVPMDVSPAF
     DGLAVE