ID FDFT_PONAB Reviewed; 417 AA. AC Q5R6U3; DT 12-JUN-2007, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 24-JAN-2024, entry version 99. DE RecName: Full=Squalene synthase; DE Short=SQS; DE Short=SS; DE EC=2.5.1.21 {ECO:0000250|UniProtKB:P37268}; DE AltName: Full=FPP:FPP farnesyltransferase; DE AltName: Full=Farnesyl-diphosphate farnesyltransferase; GN Name=FDFT1; OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Pongo. OX NCBI_TaxID=9601; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain cortex; RG The German cDNA consortium; RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Catalyzes the condensation of 2 farnesyl pyrophosphate (FPP) CC moieties to form squalene. Proceeds in two distinct steps. In the first CC half-reaction, two molecules of FPP react to form the stable CC presqualene diphosphate intermediate (PSQPP), with concomitant release CC of a proton and a molecule of inorganic diphosphate. In the second CC half-reaction, PSQPP undergoes heterolysis, isomerization, and CC reduction with NADPH or NADH to form squalene. It is the first CC committed enzyme of the sterol biosynthesis pathway. CC {ECO:0000250|UniProtKB:P37268}. 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 Evidence={ECO:0000250|UniProtKB:P37268}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32296; CC Evidence={ECO:0000250|UniProtKB:P37268}; 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 Evidence={ECO:0000250|UniProtKB:P37268}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32300; CC Evidence={ECO:0000250|UniProtKB:P37268}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + NADH + presqualene diphosphate = diphosphate + NAD(+) + CC squalene; Xref=Rhea:RHEA:22228, ChEBI:CHEBI:15378, ChEBI:CHEBI:15440, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57310, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945; Evidence={ECO:0000250|UniProtKB:P37268}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22229; CC Evidence={ECO:0000250|UniProtKB:P37268}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + NADPH + presqualene diphosphate = diphosphate + NADP(+) CC + squalene; Xref=Rhea:RHEA:22232, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15440, ChEBI:CHEBI:33019, ChEBI:CHEBI:57310, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000250|UniProtKB:P37268}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22233; CC Evidence={ECO:0000250|UniProtKB:P37268}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 (2E,6E)-farnesyl diphosphate = diphosphate + presqualene CC diphosphate; Xref=Rhea:RHEA:22672, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:57310, ChEBI:CHEBI:175763; CC Evidence={ECO:0000250|UniProtKB:P37268}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22673; CC Evidence={ECO:0000250|UniProtKB:P37268}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P37268}; CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from CC farnesyl diphosphate: step 1/3. {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q02769}; Multi-pass membrane protein CC {ECO:0000255}. 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; CR860391; CAH92517.1; -; mRNA. DR RefSeq; NP_001126476.1; NM_001133004.2. DR AlphaFoldDB; Q5R6U3; -. DR SMR; Q5R6U3; -. DR STRING; 9601.ENSPPYP00000020559; -. DR Ensembl; ENSPPYT00000021386.2; ENSPPYP00000020559.1; ENSPPYG00000018346.3. DR GeneID; 100173463; -. DR KEGG; pon:100173463; -. DR CTD; 2222; -. DR eggNOG; KOG1459; Eukaryota. DR GeneTree; ENSGT00390000016034; -. DR InParanoid; Q5R6U3; -. DR OrthoDB; 5487739at2759; -. DR TreeFam; TF105316; -. DR UniPathway; UPA00767; UER00751. DR Proteomes; UP000001595; Chromosome 8. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0004310; F:farnesyl-diphosphate farnesyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0051996; F:squalene synthase activity; IEA:UniProtKB-EC. DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW. 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 2: Evidence at transcript level; KW Cholesterol biosynthesis; Cholesterol metabolism; Endoplasmic reticulum; KW Isoprene biosynthesis; Lipid biosynthesis; Lipid metabolism; Magnesium; KW Membrane; Metal-binding; Multifunctional enzyme; NAD; NADP; KW Reference proteome; Steroid biosynthesis; Steroid metabolism; KW Sterol biosynthesis; Sterol metabolism; Transferase; Transmembrane; KW Transmembrane helix. FT CHAIN 1..417 FT /note="Squalene synthase" FT /id="PRO_0000290006" FT TRANSMEM 284..304 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 384..404 FT /note="Helical" FT /evidence="ECO:0000255" FT BINDING 52 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P37268" FT BINDING 77 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P37268" FT BINDING 80 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P37268" FT BINDING 83 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P37268" FT BINDING 84 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P37268" FT BINDING 218 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P37268" FT BINDING 315 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P37268" FT BINDING 317 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P37268" SQ SEQUENCE 417 AA; 48115 MW; D36CBC8382F827EC CRC64; MEFVKCLGHP EEFYNLVRFR IGGKRKVMPK MDQDSLSSSL KTCYKYLNQT SRSFAAVIQA LDGEMRNAVC IFYLVLRALD TLEDDMTISV EKKVPLLHNF HSFLYQPDWR FMESKEKDRQ VLEDFPTISL EFRNLAEKYQ TVIADICRRM GIGMAEFLDK HVTSEQEWDK YCHYVAGLVG IGLSRLFSAS EFEDPLVGED TERANSMGLF LQKTNIIRDY LEDQQGGREF WPQEVWSRYV KKLGDFAKPE NIDLAVQCLN ELITNALHHI PDVITYLSRL RNQSVFNFCA IPQVMAIATL AACYNNQQVF KGAVKIRKGQ AVTLMMDATN MPAVKAIIYQ YMEEIYHRIP DSDPSSSKTR QIISTIRTQN LPNCQLISRS HYSPIYLSFV MLLAALSWQY LTTLSQVTED YVQTGEH //