ID   ERG13_SCHPO             Reviewed;         447 AA.
AC   P54874;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   03-AUG-2022, entry version 150.
DE   RecName: Full=Hydroxymethylglutaryl-CoA synthase {ECO:0000303|PubMed:8750242};
DE            Short=HMG-CoA synthase {ECO:0000303|PubMed:8750242};
DE            EC=2.3.3.10 {ECO:0000305|PubMed:8750242};
DE   AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase {ECO:0000303|PubMed:8750242};
GN   Name=hcs1 {ECO:0000303|PubMed:8750242}; Synonyms=hcs; ORFNames=SPAC4F8.14c;
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 [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP   PATHWAY.
RX   PubMed=8750242; DOI=10.1002/yea.320111509;
RA   Katayama S., Adachi N., Takao K., Nakagawa T., Matsuda H., Kawamukai M.;
RT   "Molecular cloning and sequencing of the hcs gene, which encodes 3-hydroxy-
RT   3-methylglutaryl coenzyme A synthase of Schizosaccharomyces pombe.";
RL   Yeast 11:1533-1537(1995).
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   FUNCTION.
RX   PubMed=8896278;
RX   DOI=10.1002/(sici)1097-0061(19960915)12:11<1107::aid-yea992>3.0.co;2-e;
RA   Lum P.Y., Edwards S., Wright R.;
RT   "Molecular, functional and evolutionary characterization of the gene
RT   encoding HMG-CoA reductase in the fission yeast, Schizosaccharomyces
RT   pombe.";
RL   Yeast 12:1107-1124(1996).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-398, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RX   PubMed=18257517; DOI=10.1021/pr7006335;
RA   Wilson-Grady J.T., Villen J., Gygi S.P.;
RT   "Phosphoproteome analysis of fission yeast.";
RL   J. Proteome Res. 7:1088-1097(2008).
RN   [5]
RP   FUNCTION.
RX   PubMed=19486165; DOI=10.1111/j.1365-2443.2009.01308.x;
RA   Fang Y., Imagawa K., Zhou X., Kita A., Sugiura R., Jaiseng W., Kuno T.;
RT   "Pleiotropic phenotypes caused by an opal nonsense mutation in an essential
RT   gene encoding HMG-CoA reductase in fission yeast.";
RL   Genes Cells 14:759-771(2009).
CC   -!- FUNCTION: Hydroxymethylglutaryl-CoA synthase; part of the first module
CC       of ergosterol biosynthesis pathway that includes the early steps of the
CC       pathway, conserved across all eukaryotes, and which results in the
CC       formation of mevalonate from acetyl-coenzyme A (acetyl-CoA)
CC       (PubMed:8750242). Hcs1 condenses acetyl-CoA with acetoacetyl-CoA to
CC       form hydroxymethylglutaryl-CoA (HMG-CoA) (PubMed:8750242). The first
CC       module starts with the action of the cytosolic acetyl-CoA
CC       acetyltransferase eg10 that catalyzes the formation of acetoacetyl-CoA.
CC       The hydroxymethylglutaryl-CoA synthases erg13 then condenses acetyl-CoA
CC       with acetoacetyl-CoA to form HMG-CoA. The rate-limiting step of the
CC       early module is the reduction to mevalonate by the 3-hydroxy-3-
CC       methylglutaryl-coenzyme A (HMG-CoA) reductases hcs1 (Probable).
CC       {ECO:0000269|PubMed:8750242, ECO:0000305}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetoacetyl-CoA + acetyl-CoA + H2O = (3S)-hydroxy-3-
CC         methylglutaryl-CoA + CoA + H(+); Xref=Rhea:RHEA:10188,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43074,
CC         ChEBI:CHEBI:57286, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.3.10;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU10116,
CC         ECO:0000305|PubMed:8750242};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10189;
CC         Evidence={ECO:0000305|PubMed:8750242};
CC   -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC       biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
CC       {ECO:0000269|PubMed:8750242}.
CC   -!- DISRUPTION PHENOTYPE: Impairs growth in absence of mevalonate.
CC       {ECO:0000269|PubMed:8750242}.
CC   -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC       family. {ECO:0000305}.
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DR   EMBL; U32187; AAB17601.1; -; Genomic_DNA.
DR   EMBL; CU329670; CAB11060.1; -; Genomic_DNA.
DR   PIR; S61875; S61875.
DR   RefSeq; NP_593859.1; NM_001019288.2.
DR   AlphaFoldDB; P54874; -.
DR   SMR; P54874; -.
DR   STRING; 4896.SPAC4F8.14c.1; -.
DR   iPTMnet; P54874; -.
DR   MaxQB; P54874; -.
DR   PaxDb; P54874; -.
DR   PRIDE; P54874; -.
DR   EnsemblFungi; SPAC4F8.14c.1; SPAC4F8.14c.1:pep; SPAC4F8.14c.
DR   PomBase; SPAC4F8.14c; hcs1.
DR   VEuPathDB; FungiDB:SPAC4F8.14c; -.
DR   eggNOG; KOG1393; Eukaryota.
DR   HOGENOM; CLU_008065_0_1_1; -.
DR   OMA; DDAYNWI; -.
DR   PhylomeDB; P54874; -.
DR   BRENDA; 2.3.3.10; 5613.
DR   Reactome; R-SPO-191273; Cholesterol biosynthesis.
DR   Reactome; R-SPO-77111; Synthesis of Ketone Bodies.
DR   UniPathway; UPA00058; UER00102.
DR   PRO; PR:P54874; -.
DR   Proteomes; UP000002485; Chromosome I.
DR   GO; GO:0005829; C:cytosol; HDA:PomBase.
DR   GO; GO:0005783; C:endoplasmic reticulum; IC:PomBase.
DR   GO; GO:0005634; C:nucleus; HDA:PomBase.
DR   GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IMP:PomBase.
DR   GO; GO:0006084; P:acetyl-CoA metabolic process; IMP:PomBase.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; IMP:PomBase.
DR   GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IMP:PomBase.
DR   Gene3D; 3.40.47.10; -; 1.
DR   InterPro; IPR000590; HMG_CoA_synt_AS.
DR   InterPro; IPR013746; HMG_CoA_synt_C_dom.
DR   InterPro; IPR013528; HMG_CoA_synth_N.
DR   InterPro; IPR010122; HMG_CoA_synthase_euk.
DR   InterPro; IPR016039; Thiolase-like.
DR   Pfam; PF08540; HMG_CoA_synt_C; 1.
DR   Pfam; PF01154; HMG_CoA_synt_N; 1.
DR   SUPFAM; SSF53901; SSF53901; 2.
DR   TIGRFAMs; TIGR01833; HMG-CoA-S_euk; 1.
DR   PROSITE; PS01226; HMG_COA_SYNTHASE; 1.
PE   1: Evidence at protein level;
KW   Lipid biosynthesis; Lipid metabolism; Phosphoprotein; Reference proteome;
KW   Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW   Sterol metabolism; Transferase.
FT   CHAIN           1..447
FT                   /note="Hydroxymethylglutaryl-CoA synthase"
FT                   /id="PRO_0000213757"
FT   ACT_SITE        86
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT   ACT_SITE        118
FT                   /note="Acyl-thioester intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT   ACT_SITE        250
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT   MOD_RES         398
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:18257517"
SQ   SEQUENCE   447 AA;  49239 MW;  919BDDBD9207B886 CRC64;
     MSFDRKDIGI KGLVLYTPNQ YVEQAALEAH DGVSTGKYTI GLGLTKMAFV DDREDIYSFG
     LTALSQLIKR YQIDISKIGR LEVGTETIID KSKSVKSVLM QLFGDNHNVE GIDCVNACYG
     GVNALFNTID WIESSAWDGR DGIVVAGDIA LYAKGNARPT GGAGCVALLV GPNAPIVFEP
     GLRGTYMQHA YDFYKPDLTS EYPYVDGHFS LECYVKALDG AYANYNVRDV AKNGKSQGLG
     LDRFDYCIFH APTCKQVQKA YARLLYTDSA AEPSNPELEG VRELLSTLDA KKSLTDKALE
     KGLMAITKER FNKRVSPSVY APTNCGNMYT ASIFSCLTAL LSRVPADELK GKRVGAYSYG
     SGLAASFFSF VVKGDVSEIA KKTNLVNDLD NRHCLTPTQY EEAIELRHQA HLKKNFTPKG
     SIERLRSGTY YLTGIDDMFR RSYSVKP