2.5.1.21	evolution	phylogenetic analysis of SQS enzymes in plants shows highly similar conserved pattern including 77DTVED81 and 213DYLED217 motifs, which are rich in aspartic acids involved in FPP binding	739735	
2.5.1.21	evolution	the enzyme belongs to the isoprenoid biosynthesis enzymes class 1 superfamily	-, 738798	
2.5.1.21	malfunction	enzyme overexpression in transgenic Withania somnifera plants affects the shoot elongation and multiplication, phenotype, overview	739290	
2.5.1.21	malfunction	Inhibition of squalene synthase leads directly to a reduction in cholesterol biosynthesis and thus to a fall in plasma cholesterol levels. Plasma LDL-cholesterol and triglycerides are lowered by squalene synthase inhibitors	721802	
2.5.1.21	malfunction	modifications in region IV prevents SQS from undergoing the second half-reaction, indicating that this region may reasonably constitute a functional NADPH binding site	722759	
2.5.1.21	malfunction	the SQS inhibitors YM-53601 and zaragozic acid A decrease hepatitis C virus RNA, protein, and progeny production in HCV-infected cells without affecting cell viability, using the HCV JFH-1 strain and human hepatoma Huh-7.5.1-derived cells. siRNA-mediated knockdown of SQS leads to significantly reduced HCV production, confirming the enzyme acts as an antiviral target. A metabolic labeling study demonstrates that enzyme inhibitor YM-53601 suppresses the biosynthesis of cholesterol and cholesteryl esters at antiviral concentrations	738940	
2.5.1.21	metabolism	enzyme SQS operates at a branch point of the withanolide biosynthetic pathway regulating the metabolic flux and catalyzes the first committed step leading to the synthesis of different withanolides	739290	
2.5.1.21	metabolism	four major steps - substrate binding, condensation, intermediate formation and translocation - of the ordered sequential mechanisms involved in the 1'-1 isoprenoid biosynthetic pathway	737345	
2.5.1.21	metabolism	key enzyme in the isoprenoid pathway	706801	
2.5.1.21	metabolism	part of cholesterol biosynthesis pathway	703278	
2.5.1.21	metabolism	part of cholesterol synthesis pathway	697143	
2.5.1.21	metabolism	squalene synthase catalyzes the committed step of sterol synthesis	722759	
2.5.1.21	metabolism	squalene synthase catalyzes the conversion of farnesyl pyrophosphate into squalene by reductive condensation. This is a crucial step in cholesterol biosynthesis, squalene serves as the exclusive precursor for cholesterol	721802	
2.5.1.21	metabolism	squalene synthase catalyzes the first committed step in sterol biosynthesis	737775	
2.5.1.21	metabolism	squalene synthase catalyzes the first committed step in sterol biosynthesis, role of squalene synthase in the ergosterol biosynthetic pathway of budding yeast, overview	737775	
2.5.1.21	metabolism	squalene synthase catalyzes the first enzymatic step from the central isoprenoid pathway toward sterol and triterpenoid biosynthesis	759351	
2.5.1.21	metabolism	squalene synthase catalyzes the first enzymatic step of the central isoprenoid pathway in sterol and triterpenoid biosynthesis	723497	
2.5.1.21	metabolism	squalene synthase catalyzes the first step of sterol/hopanoid biosynthesis in the organism	738235	
2.5.1.21	metabolism	squalene synthase is a key enzyme in the regulation of isoprenoid biosynthesis and is important in the withanolides biosynthesis pathway, overview	723148	
2.5.1.21	metabolism	squalene synthase is a key enzyme involved in antifungal steroidal glycoalkaloids biosynthesis. Steroidal glycoalkaloids are a family of nitrogenous secondary metabolites acting as phytoalexins, e.g. gamma-solamargine and its aglycone solasodine from Solanum nigrum inhibiting hyphae formation of Fusarium oxysporum	722107	
2.5.1.21	metabolism	squalene synthase is a major enzyme in the sterol biosynthetic pathway	-, 722293	
2.5.1.21	metabolism	squalene synthase is the key enzyme of saponin biosynthesis pathway	723165	
2.5.1.21	metabolism	the enzyme catalyzes a key steps in the biosynthesis of cyclic terpenoids	759950	
2.5.1.21	metabolism	the enzyme catalyzes the first dedicated step in the biosynthesis of sterols and other triterpenoids	738856, 759271	
2.5.1.21	metabolism	the enzyme is a key enzyme in the isoprenoid biosynthesis	-, 738798	
2.5.1.21	metabolism	the enzyme is involved in celastrol biosynthesis	759803	
2.5.1.21	metabolism	the enzyme is involved in squalene synthesis and sterol metabolism	739406	
2.5.1.21	additional information	determination and analysis of human SQS and its mutants in complex with several substrate analogues and intermediates coordinated with Mg2+ or Mn2+, SQS active analysis, overview	737345	
2.5.1.21	additional information	enzyme overexpression leads a significant 4fold enhancement in squalene synthase activity and 2.5fold enhancement in withanolide A content, transformed cell suspension cultures also produce withaferin A, which is absent in the non-transformed cell cultures	722843	
2.5.1.21	additional information	functional analyses of the enzyme's two DXXD(E)D motifs and the highly conserved aromatic amino acid residues, kinetic analysis and reaction mechanism, overview. The potential active-site residues 58DXX61E62D (S1 site) and 213DXX216D217D (S2 site) are assumed to be involved in the binding of the substrate farnesyl diphosphate through the Mg2+ ion. The S1 site and the two basic residues R55 and K212 are responsible for the binding of farnesyl diphosphate	738214	
2.5.1.21	additional information	homology modelling of SQS enzyme of Withania somnifera for the prediction of three-dimensional structure, molecular docking study of considered substrates, overview	739037	
2.5.1.21	additional information	methyl jasmonate, abscisic acid, and ethephon induce the accumulation of BfSS1 mRNA, overexpression of the BfSS1 gene in the sense orientation in Bupleurum falcatum increases the mRNA accumulation of downstream genes such as squalene epoxidase and cycloartenol synthase but decreases the mRNA levels of beta-amyrin synthase, a triterpene synthase mRNA. Methyljasmonate treatment of transgenic roots overexpressing BfSS1 in the sense orientation fails to stimulate beta-amyrin synthase mRNA accumulation but still enhances saikosaponin and phytosterol production	723497	
2.5.1.21	additional information	molecular docking study, overview	739735	
2.5.1.21	additional information	proposed catalytic cascades for the enzyme-mediated biosynthesis of squalene and botryococcene, and molecular modeling of Botryococcus braunii botryococcene and squalene synthase enzymes, overview. Substrate docking and molecular modeling	741903	
2.5.1.21	additional information	squalene does not accumulate significantly in CrSQS-overexpressing cells, although conversion of farnesyl diphosphate to squalene is enhanced by overexpression of enzyme CrSQS	739406	
2.5.1.21	additional information	structure homology modelling using the crystal structure of human squalene synthase, PDB ID 1EZFB, as template, overview	-, 738798	
2.5.1.21	additional information	the catalytic site is composed of the large central cavity formed by antiparallel alpha helices with two aspartate rich regions (DXXXD) on opposite walls, these residues are considered to play roles in binding of prenyl phosphates by binding Mg2+ ions	723148	
2.5.1.21	additional information	the hinge domain plays an essential functional role, such as assembly of ergosterol multi-enzymecomplexes in fungi	737775	
2.5.1.21	additional information	the substrate binding site is present at the core region of the enzyme structure. The predicted active site involves Phe 204, Leu 205, Gln 206, Thr 208, Asn 209, Ala 293, and Leu 297. The aspartate side chains are involved in binding multiple Mg2+ ions that stabilize binding of diphosphate groups in the substrate.	723165	
2.5.1.21	physiological function	enzyme SQS plays an important role in regulating isoprenoid biosynthesis in eukaryotes	738856	
2.5.1.21	physiological function	essential role in embryonic development	703278	
2.5.1.21	physiological function	influence on regulation of cholesterol metabolism	697143	
2.5.1.21	physiological function	SQS play an important regulatory role in phytosterol biosynthetic pathway	739037	
2.5.1.21	physiological function	squalene and botryococcene are branched-chain, triterpene compounds that arise from the head-tohead condensation of two molecules of farnesyl diphosphate to yield 1'-1 and 1'-3 linkages, respectively	741903	
2.5.1.21	physiological function	squalene is biosynthesized via the head-to-head condensation of two molecules of farnesyl diphosphate, which is catalyzed by the single enzyme squalene synthase. Squalene is a precursor of thousands of bioactive triterpenoids	738718	
2.5.1.21	physiological function	squalene synthase catalyses an unusual head-to-head reductive dimerization of two molecules of farnesyl-pyrophosphate in a two-step reaction to form squalene	-, 722293	
2.5.1.21	physiological function	squalene synthase functions as a key regulator in channeling the carbon flux into both the primary and secondary metabolite branches, and squalene synthase may play a regulatory role in directing triterpene intermediates and sterol pathways	723497	
2.5.1.21	physiological function	squalene synthase is the rate-limiting enzyme located at the downstream of cholesterol synthesis pathway	737480	
2.5.1.21	physiological function	the catalytic domain performs the head-to-head dimerization of two molecules of farnesyl diphosphate to form squalene, a 30 carbon isoprenoid oxidized by squalene monooxygenase (Erg1) and cyclized by lanosterol synthase	737775	
2.5.1.21	physiological function	the enzyme is involved in squalene synthesis and sterol metabolism	739406	
2.5.1.21	physiological function	the enzyme squalene synthase catalyzes the first committed step in sterol biosynthesis by condensing two molecules of farnesyl diphosphate into squalene in two reaction steps	739735