ERG12_SCHPO
ID ERG12_SCHPO Reviewed; 404 AA.
AC Q09780;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Mevalonate kinase {ECO:0000250|UniProtKB:P07277};
DE Short=MK {ECO:0000250|UniProtKB:P07277};
DE EC=2.7.1.36 {ECO:0000250|UniProtKB:P07277};
GN Name=erg12; ORFNames=SPAC13G6.11c;
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 MRNA].
RC STRAIN=PR745;
RX PubMed=9501991; DOI=10.1093/dnares/4.6.363;
RA Yoshioka S., Kato K., Nakai K., Okayama H., Nojima H.;
RT "Identification of open reading frames in Schizosaccharomyces pombe
RT cDNAs.";
RL DNA Res. 4:363-369(1997).
RN [2]
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 [3]
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: Mevalonate kinase; part of the second module of ergosterol
CC biosynthesis pathway that includes the middle steps of the pathway (By
CC similarity). Erg12 converts mevalonate into 5-phosphomevalonate (By
CC similarity). 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 then produces isopentenyl diphosphate. The isopentenyl-diphosphate
CC delta-isomerase idi1 then catalyzes the 1,3-allylic rearrangement of
CC the homoallylic substrate isopentenyl (IPP) to its highly electrophilic
CC allylic isomer, dimethylallyl diphosphate (DMAPP). Finally the farnesyl
CC diphosphate synthase fps1 catalyzes the sequential condensation of
CC isopentenyl pyrophosphate with dimethylallyl pyrophosphate, and then
CC with the resultant geranylpyrophosphate to the ultimate product
CC farnesyl pyrophosphate (Probable). {ECO:0000250|UniProtKB:P07277,
CC ECO:0000305}.
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:P07277};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17066;
CC Evidence={ECO:0000250|UniProtKB:P07277};
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:0000250|UniProtKB:P07277}.
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC step 1/3. {ECO:0000250|UniProtKB:P07277}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P17256}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus
CC {ECO:0000269|PubMed:16823372}.
CC -!- SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase
CC subfamily. {ECO:0000305}.
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; AB000541; BAA25169.1; -; mRNA.
DR EMBL; CU329670; CAA91104.1; -; Genomic_DNA.
DR PIR; S62440; S62440.
DR RefSeq; NP_592837.1; NM_001018238.2.
DR AlphaFoldDB; Q09780; -.
DR SMR; Q09780; -.
DR BioGRID; 279265; 1.
DR STRING; 4896.SPAC13G6.11c.1; -.
DR MaxQB; Q09780; -.
DR PaxDb; Q09780; -.
DR EnsemblFungi; SPAC13G6.11c.1; SPAC13G6.11c.1:pep; SPAC13G6.11c.
DR GeneID; 2542818; -.
DR KEGG; spo:SPAC13G6.11c; -.
DR PomBase; SPAC13G6.11c; erg12.
DR VEuPathDB; FungiDB:SPAC13G6.11c; -.
DR eggNOG; KOG1511; Eukaryota.
DR HOGENOM; CLU_017814_0_1_1; -.
DR InParanoid; Q09780; -.
DR OMA; NTVCTYG; -.
DR PhylomeDB; Q09780; -.
DR Reactome; R-SPO-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00057; UER00098.
DR PRO; PR:Q09780; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0005634; C:nucleus; HDA:PomBase.
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; ISS:UniProtKB.
DR GO; GO:0006696; P:ergosterol biosynthetic process; ISS:PomBase.
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; 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 2: Evidence at transcript level;
KW ATP-binding; Cytoplasm; Kinase; Lipid biosynthesis; Lipid metabolism;
KW Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transferase.
FT CHAIN 1..404
FT /note="Mevalonate kinase"
FT /id="PRO_0000156661"
FT ACT_SITE 195
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 130
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 135..141
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 141
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P17256"
FT BINDING 184
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P17256"
SQ SEQUENCE 404 AA; 43407 MW; AE8B6D1646247710 CRC64;
MSKSLIVSSP GKTILFGEHA VVYGATALAA AVSLRSYCKL QTTNNNEIVI VMSDIGTERR
WNLQSLPWQH VTVENVQHPA SSPNLDLLQG LGELLKNEEN GLIHSAMLCT LYLFTSLSSP
SQGCTLTISS QVPLGAGLGS SATISVVVAT SLLLAFGNIE PPSSNSLQNN KALALIEAWS
FLGECCIHGT PSGIDNAVAT NGGLIAFRKA TAHQSAMKEF LKPKDTLSVM ITDTKQPKST
KKLVQGVFEL KERLPTVIDS IIDAIDGISK SAVLALTSES DKNSSAKKLG EFIVLNQKLL
ECLGVSHYSI DRVLQATKSI GWTKLTGAGG GGCTITLLTP ECKEEEFKLC KESLLAHKNS
IYDVQLGGPG VSVVTDSDSF FPQYESDFDF KKLNLLSKFN KYYI
