ID   FDFT_CYBJA              Reviewed;         443 AA.
AC   O74165;
DT   31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   25-MAY-2022, entry version 90.
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;
OS   Cyberlindnera jadinii (Torula yeast) (Pichia jadinii).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Phaffomycetaceae; Cyberlindnera.
OX   NCBI_TaxID=4903;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX   PubMed=9647847; DOI=10.1128/aem.64.7.2676-2680.1998;
RA   Shimada H., Kondo K., Fraser P.D., Miura Y., Saito T., Misawa N.;
RT   "Increased carotenoid production by the food yeast Candida utilis through
RT   metabolic engineering of the isoprenoid pathway.";
RL   Appl. Environ. Microbiol. 64:2676-2680(1998).
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. {ECO:0000269|PubMed:9647847}.
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; AB012604; BAA31938.1; -; Genomic_DNA.
DR   AlphaFoldDB; O74165; -.
DR   SMR; O74165; -.
DR   UniPathway; UPA00767; UER00751.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0004310; F:farnesyl-diphosphate farnesyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0051996; F:squalene synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR   CDD; cd00683; Trans_IPPS_HH; 1.
DR   Gene3D; 1.10.600.10; -; 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   PANTHER; PTHR11626; PTHR11626; 1.
DR   Pfam; PF00494; SQS_PSY; 1.
DR   SUPFAM; SSF48576; SSF48576; 1.
DR   TIGRFAMs; TIGR01559; squal_synth; 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   Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW   Sterol metabolism; Transferase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..443
FT                   /note="Squalene synthase"
FT                   /id="PRO_0000067450"
FT   TRANSMEM        291..311
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        423..443
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   443 AA;  50954 MW;  E7231500BBF5D82B CRC64;
     MGKLLQLALH PDELASIVQF KLFRKNENAR NPATESAELI RCYELLNLTS RSFAAVIEEL
     HPELRNVIMV FYLVLRALDT VEVDMSIENS VKLPVLRQFH EKLDTKDWTF DGNSPNEKDR
     CVLVEFDRIL GQYHELKPQY QKVIKEITEK MGNGMADYIE NENFNSNGLL TIEDYDLYCY
     YVAGLVGDGL TQLIVLAKFG NSELSVNKQL FKSMGLFLQK TNIIRDYEED QVDGRAFWPK
     EIWGKYANEL SDFMKPENQS QGLWCISELV CNALDHVIDV LQYLALVEEQ TSFNFCAIPQ
     VMAIATLELV FQNPQVLTQH VKIRKGTTVS LILESRTLEG CARIFRRYLR KIHHKSHPSD
     PNYLRLGITI GKIEQFLDGM YPHYVPKGIT PQTTSIRTQV VKRLQLDEPM KRDIDEEILK
     TRILLLSLGV AVFGVVYGVV RII