ID   FDFT_DICDI              Reviewed;         416 AA.
AC   Q54DR1;
DT   08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   24-MAY-2005, sequence version 1.
DT   24-JAN-2024, entry version 108.
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=fdfT; ORFNames=DDB_G0292072;
OS   Dictyostelium discoideum (Social amoeba).
OC   Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC   Dictyosteliaceae; Dictyostelium.
OX   NCBI_TaxID=44689;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=12097910; DOI=10.1038/nature00847;
RA   Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA   Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA   Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA   Noegel A.A.;
RT   "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL   Nature 418:79-85(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=15875012; DOI=10.1038/nature03481;
RA   Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA   Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA   Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA   Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA   Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA   Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA   Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA   Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA   Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA   Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA   Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA   Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA   Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA   Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA   Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA   Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA   Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT   "The genome of the social amoeba Dictyostelium discoideum.";
RL   Nature 435:43-57(2005).
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; AAFI02000187; EAL61392.1; -; Genomic_DNA.
DR   RefSeq; XP_629811.1; XM_629809.1.
DR   AlphaFoldDB; Q54DR1; -.
DR   SMR; Q54DR1; -.
DR   STRING; 44689.Q54DR1; -.
DR   PaxDb; 44689-DDB0231376; -.
DR   EnsemblProtists; EAL61392; EAL61392; DDB_G0292072.
DR   GeneID; 8628492; -.
DR   KEGG; ddi:DDB_G0292072; -.
DR   dictyBase; DDB_G0292072; fdfT.
DR   eggNOG; KOG1459; Eukaryota.
DR   HOGENOM; CLU_031981_0_2_1; -.
DR   InParanoid; Q54DR1; -.
DR   OMA; GEACQLM; -.
DR   PhylomeDB; Q54DR1; -.
DR   Reactome; R-DDI-191273; Cholesterol biosynthesis.
DR   UniPathway; UPA00767; UER00751.
DR   PRO; PR:Q54DR1; -.
DR   Proteomes; UP000002195; Chromosome 6.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR   GO; GO:0004310; F:farnesyl-diphosphate farnesyltransferase activity; ISS:dictyBase.
DR   GO; GO:0051996; F:squalene synthase activity; IBA:GO_Central.
DR   GO; GO:0006695; P:cholesterol biosynthetic process; ISS:dictyBase.
DR   GO; GO:0045338; P:farnesyl diphosphate metabolic process; IBA:GO_Central.
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   Cholesterol biosynthesis; Cholesterol metabolism; Endoplasmic reticulum;
KW   Isoprene biosynthesis; Lipid biosynthesis; Lipid metabolism; Magnesium;
KW   Membrane; Multifunctional enzyme; NADP; Reference proteome;
KW   Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW   Sterol metabolism; Transferase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..416
FT                   /note="Squalene synthase"
FT                   /id="PRO_0000327603"
FT   TRANSMEM        285..304
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        386..406
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   416 AA;  47504 MW;  02CDC89C06D3DD20 CRC64;
     MQYMKSLAHP DEFLSLLKIG YTESFKPKSQ LKENLGNKEW CYELLNKTSR SFAFVINELE
     PSLKDAICIF YLVLRGLDTI EDDTTVELNT KLPVLTSFSE GLYQPGYKVF GYGMNNDEKN
     LVENFDKVVD VFLGLGDGYC TIIHDITRRM ANGMSEFLQK SVVTLPEWDL YCHYVAGLVG
     IGLSKIFHAS GLESEWFATA DDESNQMGLF LQKTNIIRDY LEDINEKRIF WPRDVWARYT
     LHLENFKEAK YQIPALHCLN DLITNALSHA LIALDYMSRL KNPQVINFCA IPQVMAIGTL
     NACYNNYNVF TGVVKIRKGQ RALIVDAIQS KGLTATYELF FKFANEMRHK VPPNDPSAKK
     TIQHLESIEK LCIEKLGYRP SGFNDFISYD WMAVTSLAVS SAFLIARHGP NFFSKL
//