ID   FDFT_CANGA              Reviewed;         443 AA.
AC   Q9HGZ6; Q6FJD8;
DT   10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT   31-AUG-2004, sequence version 2.
DT   24-JAN-2024, entry version 139.
DE   RecName: Full=Squalene synthase;
DE            Short=SQS;
DE            Short=SS;
DE            EC=2.5.1.21;
DE   AltName: Full=FPP:FPP farnesyltransferase;
DE   AltName: Full=Farnesyl-diphosphate farnesyltransferase;
GN   Name=ERG9; OrderedLocusNames=CAGL0M07095g;
OS   Candida glabrata (strain ATCC 2001 / BCRC 20586 / JCM 3761 / NBRC 0622 /
OS   NRRL Y-65 / CBS 138) (Yeast) (Nakaseomyces glabratus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Nakaseomyces.
OX   NCBI_TaxID=284593;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 2001 / BCRC 20586 / JCM 3761 / NBRC 0622 / NRRL Y-65 / CBS
RC   138;
RX   PubMed=10952588; DOI=10.1128/aac.44.9.2411-2418.2000;
RA   Nakayama H., Izuta M., Nakayama N., Arisawa M., Aoki Y.;
RT   "Depletion of the squalene synthase (ERG9) gene does not impair growth of
RT   Candida glabrata in mice.";
RL   Antimicrob. Agents Chemother. 44:2411-2418(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 2001 / BCRC 20586 / JCM 3761 / NBRC 0622 / NRRL Y-65 / CBS
RC   138;
RX   PubMed=15229592; DOI=10.1038/nature02579;
RA   Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA   de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA   Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA   Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA   Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA   Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA   Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA   Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA   Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA   Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA   Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA   Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA   Weissenbach J., Wincker P., Souciet J.-L.;
RT   "Genome evolution in yeasts.";
RL   Nature 430:35-44(2004).
CC   -!- FUNCTION: Catalyzes the condensation of 2 two farnesyl pyrophosphate
CC       moieties to form squalene. It is the first committed enzyme of the
CC       sterol biosynthesis pathway. Required for the biosynthesis of
CC       ergosterol.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 (2E,6E)-farnesyl diphosphate + H(+) + NADPH = 2 diphosphate
CC         + NADP(+) + squalene; Xref=Rhea:RHEA:32295, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15440, ChEBI:CHEBI:33019, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349, ChEBI:CHEBI:175763; EC=2.5.1.21;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 (2E,6E)-farnesyl diphosphate + H(+) + NADH = 2 diphosphate +
CC         NAD(+) + squalene; Xref=Rhea:RHEA:32299, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15440, ChEBI:CHEBI:33019, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945, ChEBI:CHEBI:175763; EC=2.5.1.21;
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC   -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC       farnesyl diphosphate: step 1/3.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC       Multi-pass membrane protein {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the phytoene/squalene synthase family.
CC       {ECO:0000305}.
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DR   EMBL; AB009978; BAB12207.1; -; Genomic_DNA.
DR   EMBL; CR380959; CAG62632.1; -; Genomic_DNA.
DR   RefSeq; XP_449656.1; XM_449656.1.
DR   AlphaFoldDB; Q9HGZ6; -.
DR   SMR; Q9HGZ6; -.
DR   STRING; 284593.Q9HGZ6; -.
DR   EnsemblFungi; CAGL0M07095g-T; CAGL0M07095g-T-p1; CAGL0M07095g.
DR   GeneID; 2891705; -.
DR   KEGG; cgr:CAGL0M07095g; -.
DR   CGD; CAL0136937; ERG9.
DR   VEuPathDB; FungiDB:B1J91_M07095g; -.
DR   VEuPathDB; FungiDB:CAGL0M07095g; -.
DR   eggNOG; KOG1459; Eukaryota.
DR   HOGENOM; CLU_031981_2_1_1; -.
DR   InParanoid; Q9HGZ6; -.
DR   OMA; GEACQLM; -.
DR   UniPathway; UPA00767; UER00751.
DR   Proteomes; UP000002428; Chromosome M.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004310; F:farnesyl-diphosphate farnesyltransferase activity; IMP:CGD.
DR   GO; GO:0051996; F:squalene synthase activity; IMP:CGD.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; IMP:CGD.
DR   GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:UniProtKB-KW.
DR   CDD; cd00683; Trans_IPPS_HH; 1.
DR   Gene3D; 1.10.600.10; Farnesyl Diphosphate Synthase; 1.
DR   InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR   InterPro; IPR002060; Squ/phyt_synthse.
DR   InterPro; IPR006449; Squal_synth-like.
DR   InterPro; IPR019845; Squalene/phytoene_synthase_CS.
DR   InterPro; IPR044844; Trans_IPPS_euk-type.
DR   InterPro; IPR033904; Trans_IPPS_HH.
DR   NCBIfam; TIGR01559; squal_synth; 1.
DR   PANTHER; PTHR11626; FARNESYL-DIPHOSPHATE FARNESYLTRANSFERASE; 1.
DR   PANTHER; PTHR11626:SF2; SQUALENE SYNTHASE; 1.
DR   Pfam; PF00494; SQS_PSY; 1.
DR   SFLD; SFLDS00005; Isoprenoid_Synthase_Type_I; 1.
DR   SFLD; SFLDG01018; Squalene/Phytoene_Synthase_Lik; 1.
DR   SUPFAM; SSF48576; Terpenoid synthases; 1.
DR   PROSITE; PS01044; SQUALEN_PHYTOEN_SYN_1; 1.
DR   PROSITE; PS01045; SQUALEN_PHYTOEN_SYN_2; 1.
PE   3: Inferred from homology;
KW   Endoplasmic reticulum; Isoprene biosynthesis; Lipid biosynthesis;
KW   Lipid metabolism; Magnesium; Membrane; Multifunctional enzyme; NADP;
KW   Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW   Sterol biosynthesis; Sterol metabolism; Transferase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..443
FT                   /note="Squalene synthase"
FT                   /id="PRO_0000067448"
FT   TRANSMEM        181..201
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        294..314
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        217
FT                   /note="M -> L (in Ref. 1; BAB12207)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   443 AA;  51397 MW;  C23BC9D603E44C9F CRC64;
     MGKVLDLALH PLELRAALKL KFIRQPLFST NDTRATPQLE RCYELLNLTS RSFAAVIMEL
     HPELRNVIMV FYLILRALDT VEDDMTIDPQ LKVKVLREFD SKLDTTDWSF DGNDLKEKDR
     VVLTEFPCIL GEYHKLKPEY QKVIKRITGL MGNGMADYIL DENFNLNGVQ TVKDYDKYCH
     YVAGLVGDGL TELIVLAGFG SDDLYHGKNS FQLYESMGLF LQKTNIIRDY AEDLDDGRSF
     WPKEIWSEYA TKLTDFRDPK NTQKGVDCIN HLVLNALTHV IDVLTYLSSI HEQSSFQFCA
     IPQVMAIATL AKVFNNPEVL RKNVKIRKGT TCDLILNSRT LKGCVDIFQY YLRDMKQRLP
     VEDPNYLKFN IQVAKIEQFI EEMFQDNLPA GVEPRETMIY LKVQERLKWD TQVIPRVQEE
     DYKFNMALSV VFCVLLSFYF FTK
//