ID FDFT_EREGS Reviewed; 441 AA. AC Q752X9; DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 24-JAN-2024, entry version 116. 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=AFR444C; OS Eremothecium gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL OS Y-1056) (Yeast) (Ashbya gossypii). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Eremothecium. OX NCBI_TaxID=284811; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056; RX PubMed=15001715; DOI=10.1126/science.1095781; RA Dietrich F.S., Voegeli S., Brachat S., Lerch A., Gates K., Steiner S., RA Mohr C., Poehlmann R., Luedi P., Choi S., Wing R.A., Flavier A., RA Gaffney T.D., Philippsen P.; RT "The Ashbya gossypii genome as a tool for mapping the ancient Saccharomyces RT cerevisiae genome."; RL Science 304:304-307(2004). RN [2] RP GENOME REANNOTATION. RC STRAIN=ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056; RX PubMed=23749448; DOI=10.1534/g3.112.002881; RA Dietrich F.S., Voegeli S., Kuo S., Philippsen P.; RT "Genomes of Ashbya fungi isolated from insects reveal four mating-type RT loci, numerous translocations, lack of transposons, and distinct gene RT duplications."; RL G3 (Bethesda) 3:1225-1239(2013). 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 (By similarity). {ECO:0000250}. 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}. 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; AE016819; AAS53815.1; -; Genomic_DNA. DR RefSeq; NP_985991.1; NM_211346.1. DR AlphaFoldDB; Q752X9; -. DR SMR; Q752X9; -. DR STRING; 284811.Q752X9; -. DR EnsemblFungi; AAS53815; AAS53815; AGOS_AFR444C. DR GeneID; 4622268; -. DR KEGG; ago:AGOS_AFR444C; -. DR eggNOG; KOG1459; Eukaryota. DR HOGENOM; CLU_031981_2_1_1; -. DR InParanoid; Q752X9; -. DR OMA; GEACQLM; -. DR OrthoDB; 5487739at2759; -. DR UniPathway; UPA00767; UER00751. DR Proteomes; UP000000591; Chromosome VI. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central. DR GO; GO:0004310; F:farnesyl-diphosphate farnesyltransferase activity; IBA:GO_Central. DR GO; GO:0051996; F:squalene synthase activity; IBA:GO_Central. DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central. 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 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..441 FT /note="Squalene synthase" FT /id="PRO_0000067446" FT TRANSMEM 293..313 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 420..440 FT /note="Helical" FT /evidence="ECO:0000255" SQ SEQUENCE 441 AA; 50873 MW; 53807044FB95195B CRC64; MGKVVQLFTH PLELKAALKL KFLREPLYPA DDTQGSAELK RCYQLLQRTS RSFAAVIMEL HPELRNAVML FYLILRALDT VEDDMTISPK VKVPLLREFD QKLKLDTWSF DGNAKTEKDR DVLVEFSTIL AEFHKLKPEY QQVIADITHK MGNGMADYIL DEKFNLSGLE TIQDYDRYCH YVAGLVGDGL THLIMLAKFS SPGLYYDSPD LYESMGLFLQ KTNIIRDYAE DLADGRSFWP KEIWSHYADD LASFSKPENA TAGVYCINHL VLNALGHVQH VLTYLASLRE QSSFQFCAIP QVMAIATLAL VFGNERVLQT SVKIRKGTTC YLILKSRTFQ GCVEIFEHYL RDIRKRLTVA DPNYLKLNIE IAKLDKFIEE MYQDKLPVGA KPQETEIYKK VRERSAYDLE VLPREQEEEF KFNVLLSILF TVFGALYWYA K //