ID FDFT_HUMAN Reviewed; 417 AA. AC P37268; B3KQ95; B4DJE5; B4DT56; B7Z1J3; Q96GT0; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1994, sequence version 1. DT 02-SEP-2026, entry version 237. DE RecName: Full=Squalene synthase; DE Short=SQS; DE Short=SS; DE EC=2.5.1.21 {ECO:0000269|PubMed:10896663, ECO:0000269|PubMed:24531458}; DE AltName: Full=FPP:FPP farnesyltransferase; DE AltName: Full=Farnesyl-diphosphate farnesyltransferase; DE AltName: Full=Farnesyl-diphosphate farnesyltransferase 1 {ECO:0000312|HGNC:HGNC:3629}; GN Name=FDFT1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8474436; DOI=10.1128/mcb.13.5.2706-2717.1993; RA Robinson G.W., Tsay Y.H., Kienzle B.K., Smith-Monroy C.A., Bishop R.W.; RT "Conservation between human and fungal squalene synthetases: similarities RT in structure, function, and regulation."; RL Mol. Cell. Biol. 13:2706-2717(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=7685352; DOI=10.1016/s0021-9258(18)31461-3; RA Jiang G., McKenzie T.L., Conrad D.G., Shechter I.; RT "Transcriptional regulation by lovastatin and 25-hydroxycholesterol in RT HepG2 cells and molecular cloning and expression of the cDNA for the human RT hepatic squalene synthase."; RL J. Biol. Chem. 268:12818-12824(1993). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=8294001; DOI=10.1016/0378-1119(93)90462-c; RA Summers C., Karst F., Charles A.D.; RT "Cloning, expression and characterisation of the cDNA encoding human RT hepatic squalene synthase, and its relationship to phytoene synthase."; RL Gene 136:185-192(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=7864626; DOI=10.1006/abbi.1995.1095; RA Soltis D.A., McMahon G., Caplan S.L., Dudas D.A., Chamberlin H.A., RA Vattay A., Dottavio D., Rucker M.L., Engstrom R.G., Cornell-Kennon S.A.; RT "Expression, purification, and characterization of the human squalene RT synthase: use of yeast and baculoviral systems."; RL Arch. Biochem. Biophys. 316:713-723(1995). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 5). RC TISSUE=Cerebellum, Pericardium, Subthalamic nucleus, and Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-45. RC TISSUE=Lung, Muscle, and Urinary bladder; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [11] RP INVOLVEMENT IN SQSD, AND TISSUE SPECIFICITY. RX PubMed=29909962; DOI=10.1016/j.ajhg.2018.05.004; RA Coman D., Vissers L.E.L.M., Riley L.G., Kwint M.P., Hauck R., Koster J., RA Geuer S., Hopkins S., Hallinan B., Sweetman L., Engelke U.F.H., RA Burrow T.A., Cardinal J., McGill J., Inwood A., Gurnsey C., Waterham H.R., RA Christodoulou J., Wevers R.A., Pitt J.; RT "Squalene synthase deficiency: clinical, biochemical, and molecular RT characterization of a defect in cholesterol biosynthesis."; RL Am. J. Hum. Genet. 103:125-130(2018). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 39-370, CATALYTIC ACTIVITY, AND RP FUNCTION. RX PubMed=10896663; DOI=10.1074/jbc.m004132200; RA Pandit J., Danley D.E., Schulte G.K., Mazzalupo S., Pauly T.A., RA Hayward C.M., Hamanaka E.S., Thompson J.F., Harwood H.J. Jr.; RT "Crystal structure of human squalene synthase. A key enzyme in cholesterol RT biosynthesis."; RL J. Biol. Chem. 275:30610-30617(2000). RN [13] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 31-370 IN COMPLEX WITH MAGNESIUM RP ION, COFACTOR, NADP BINDING SITES, CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=24531458; DOI=10.1107/s1399004713026230; RA Liu C.I., Jeng W.Y., Chang W.J., Shih M.F., Ko T.P., Wang A.H.; RT "Structural insights into the catalytic mechanism of human squalene RT synthase."; RL Acta Crystallogr. D 70:231-241(2014). RN [14] RP VARIANT ARG-45, AND ASSOCIATION WITH PLASMA CHOLESTEROL LEVELS. RX PubMed=18350552; DOI=10.1002/humu.20702; RA Do R., Pare G., Montpetit A., Hudson T.J., Gaudet D., Engert J.C.; RT "K45R variant of squalene synthase increases total cholesterol levels in RT two study samples from a French Canadian population."; RL Hum. Mutat. 29:689-694(2008). 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:0000269|PubMed:10896663, ECO:0000269|PubMed:24531458}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 (2E,6E)-farnesyl diphosphate + NADPH + H(+) = squalene + 2 CC diphosphate + NADP(+); 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:0000269|PubMed:10896663}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32296; CC Evidence={ECO:0000305|PubMed:10896663}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 (2E,6E)-farnesyl diphosphate + NADH + H(+) = squalene + 2 CC diphosphate + NAD(+); 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:0000269|PubMed:10896663}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32300; CC Evidence={ECO:0000305|PubMed:10896663}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 (2E,6E)-farnesyl diphosphate = presqualene diphosphate + CC diphosphate; Xref=Rhea:RHEA:22672, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:57310, ChEBI:CHEBI:175763; CC Evidence={ECO:0000269|PubMed:10896663, ECO:0000269|PubMed:24531458}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22673; CC Evidence={ECO:0000305|PubMed:24531458}; CC -!- CATALYTIC ACTIVITY: CC Reaction=presqualene diphosphate + NADH + H(+) = squalene + diphosphate CC + NAD(+); 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:0000269|PubMed:10896663, CC ECO:0000269|PubMed:24531458}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22229; CC Evidence={ECO:0000305|PubMed:24531458}; CC -!- CATALYTIC ACTIVITY: CC Reaction=presqualene diphosphate + NADPH + H(+) = squalene + CC diphosphate + NADP(+); 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:0000269|PubMed:10896663, ECO:0000269|PubMed:24531458}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22233; CC Evidence={ECO:0000305|PubMed:24531458}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:24531458}; CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from CC farnesyl diphosphate: step 1/3. {ECO:0000305}. CC -!- INTERACTION: CC P37268; Q13520: AQP6; NbExp=3; IntAct=EBI-714550, EBI-13059134; CC P37268; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-714550, EBI-11343438; CC P37268; P04233-2: CD74; NbExp=3; IntAct=EBI-714550, EBI-12222807; CC P37268; P11912: CD79A; NbExp=3; IntAct=EBI-714550, EBI-7797864; CC P37268; O75503: CLN5; NbExp=3; IntAct=EBI-714550, EBI-1043514; CC P37268; O43889-2: CREB3; NbExp=3; IntAct=EBI-714550, EBI-625022; CC P37268; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-714550, EBI-18535450; CC P37268; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-714550, EBI-18304435; CC P37268; P48165: GJA8; NbExp=3; IntAct=EBI-714550, EBI-17458373; CC P37268; P43220: GLP1R; NbExp=2; IntAct=EBI-714550, EBI-7466542; CC P37268; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-714550, EBI-13345167; CC P37268; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-714550, EBI-10266796; CC P37268; Q6IBW4-4: NCAPH2; NbExp=3; IntAct=EBI-714550, EBI-10247000; CC P37268; Q96RD7: PANX1; NbExp=3; IntAct=EBI-714550, EBI-7037612; CC P37268; Q14973: SLC10A1; NbExp=3; IntAct=EBI-714550, EBI-3923031; CC P37268; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-714550, EBI-17295964; CC P37268; Q96MV1: TLCD4; NbExp=3; IntAct=EBI-714550, EBI-12947623; CC P37268; Q9Y320: TMX2; NbExp=3; IntAct=EBI-714550, EBI-6447886; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q02769}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=P37268-1; Sequence=Displayed; CC Name=2; CC IsoId=P37268-2; Sequence=VSP_056283; CC Name=3; CC IsoId=P37268-3; Sequence=VSP_056282; CC Name=4; CC IsoId=P37268-4; Sequence=VSP_056517; CC Name=5; CC IsoId=P37268-5; Sequence=VSP_056518; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:29909962}. CC -!- DISEASE: Squalene synthase deficiency (SQSD) [MIM:618156]: An autosomal CC recessive disorder characterized by profound developmental delay, brain CC abnormalities, 2/3 syndactyly of the toes, facial dysmorphisms, low CC total and LDL-cholesterol, and abnormal urine organic acids. CC {ECO:0000269|PubMed:29909962}. Note=The disease is caused by variants CC affecting the gene represented in this entry. 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; L06070; AAA60582.1; -; mRNA. DR EMBL; L06105; AAA36645.1; -; mRNA. DR EMBL; X69141; CAA48896.1; -; mRNA. DR EMBL; S76822; AAB33404.1; -; mRNA. DR EMBL; AK057726; BAG51957.1; -; mRNA. DR EMBL; AK293545; BAH11529.1; -; mRNA. DR EMBL; AK296043; BAG58807.1; -; mRNA. DR EMBL; AK300059; BAG61868.1; -; mRNA. DR EMBL; AK315993; BAH14364.1; -; mRNA. DR EMBL; AK316351; BAH14722.1; -; mRNA. DR EMBL; AK316531; BAH14902.1; -; mRNA. DR EMBL; AK316534; BAH14905.1; -; mRNA. DR EMBL; AC069185; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC003573; AAH03573.1; -; mRNA. DR EMBL; BC009251; AAH09251.1; -; mRNA. DR EMBL; BC029641; AAH29641.1; -; mRNA. DR CCDS; CCDS5985.1; -. [P37268-1] DR CCDS; CCDS75696.1; -. [P37268-2] DR CCDS; CCDS75697.1; -. [P37268-3] DR PIR; A45998; A45998. DR PIR; I38245; I38245. DR PIR; I52090; I52090. DR RefSeq; NP_001274671.1; NM_001287742.2. [P37268-1] DR RefSeq; NP_001274672.1; NM_001287743.2. [P37268-1] DR RefSeq; NP_001274673.1; NM_001287744.2. [P37268-2] DR RefSeq; NP_001274674.1; NM_001287745.2. [P37268-2] DR RefSeq; NP_001274676.1; NM_001287747.2. [P37268-2] DR RefSeq; NP_001274677.1; NM_001287748.2. [P37268-2] DR RefSeq; NP_001274678.1; NM_001287749.2. [P37268-2] DR RefSeq; NP_001274679.1; NM_001287750.2. DR RefSeq; NP_001274680.1; NM_001287751.2. [P37268-3] DR RefSeq; NP_001274685.1; NM_001287756.2. DR RefSeq; NP_004453.3; NM_004462.5. [P37268-1] DR PDB; 1EZF; X-ray; 2.15 A; A/B/C=31-370. DR PDB; 3ASX; X-ray; 2.00 A; A=31-370. DR PDB; 3LEE; X-ray; 3.20 A; A/B/C/D/E/F=31-370. DR PDB; 3Q2Z; X-ray; 2.00 A; A=31-370. DR PDB; 3Q30; X-ray; 2.00 A; A=31-370. DR PDB; 3V66; X-ray; 1.80 A; A=31-370. DR PDB; 3VJ8; X-ray; 1.52 A; A=31-370. DR PDB; 3VJ9; X-ray; 1.52 A; A=31-370. DR PDB; 3VJA; X-ray; 1.76 A; A/B=31-370. DR PDB; 3VJB; X-ray; 2.05 A; A/B/C/D/E/F=31-370. DR PDB; 3VJC; X-ray; 1.89 A; A/B/C/D/E/F=31-370. DR PDB; 3WC9; X-ray; 2.82 A; A/B/C/D/E/F=31-370. DR PDB; 3WCD; X-ray; 2.75 A; A/B/C/D/E/F=31-370. DR PDB; 3WCF; X-ray; 2.22 A; A/B/C/D/E/F=31-370. DR PDB; 3WCH; X-ray; 2.50 A; A/B/C/D/E/F=31-370. DR PDB; 3WCI; X-ray; 2.30 A; A/B/C/D/E/F=31-370. DR PDB; 3WCJ; X-ray; 2.20 A; A/B/C/D/E/F=31-370. DR PDB; 3WCL; X-ray; 2.24 A; A/B/C/D/E/F=31-370. DR PDB; 3WCM; X-ray; 2.06 A; A/B/C/D/E/F=31-370. DR PDB; 3WEF; X-ray; 2.35 A; A/B/C/D/E/F=31-370. DR PDB; 3WEG; X-ray; 1.75 A; A=31-370. DR PDB; 3WEH; X-ray; 1.87 A; A=31-370. DR PDB; 3WEI; X-ray; 1.79 A; A=31-370. DR PDB; 3WEJ; X-ray; 2.00 A; A=31-370. DR PDB; 3WEK; X-ray; 1.85 A; A=31-370. DR PDB; 3WSA; X-ray; 2.90 A; A/B/C/D/E/F=31-370. DR PDB; 6PYJ; X-ray; 1.44 A; C=280-288. DR PDB; 6PYV; X-ray; 1.45 A; C=280-288. DR PDB; 6PYW; X-ray; 1.38 A; C=280-288. DR PDB; 6PZ5; X-ray; 1.53 A; C=280-288. DR PDB; 8WTQ; X-ray; 2.00 A; A=31-370. DR PDB; 8WTR; X-ray; 2.00 A; A=31-370. DR AlphaFoldDB; P37268; -. DR MDRepo; P37268; -. DR SMR; P37268; -. DR BioGRID; 108516; 175. DR FunCoup; P37268; 1153. DR IntAct; P37268; 102. DR MINT; P37268; -. DR NDEx; IQUERY-CP-FDFT1; 11 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000491537; -. DR BindingDB; P37268; -. DR ChEMBL; CHEMBL3338; -. DR DrugBank; DB07780; Farnesyl diphosphate. DR DrugBank; DB05317; TAK-475. DR DrugCentral; P37268; -. DR GuidetoPHARMACOLOGY; 645; -. DR SwissLipids; SLP:000000138; -. DR GlyGen; P37268; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P37268; -. DR MetOSite; P37268; -. DR PhosphoSitePlus; P37268; -. DR SwissPalm; P37268; -. DR BioMuta; FDFT1; -. DR DMDM; 585126; -. DR jPOST; P37268; -. DR MassIVE; P37268; -. DR PaxDb; 9606-ENSP00000491537; -. DR PeptideAtlas; P37268; -. DR ProteomicsDB; 3554; -. DR ProteomicsDB; 4370; -. DR ProteomicsDB; 5075; -. DR ProteomicsDB; 55271; -. [P37268-1] DR ProteomicsDB; 6339; -. DR Pumba; P37268; -. DR Antibodypedia; 1355; 459 antibodies from 35 providers. DR DNASU; 2222; -. DR Ensembl; ENST00000220584.9; ENSP00000220584.4; ENSG00000079459.15. [P37268-1] DR Ensembl; ENST00000443614.6; ENSP00000390367.2; ENSG00000079459.15. [P37268-5] DR Ensembl; ENST00000528643.5; ENSP00000431649.1; ENSG00000079459.15. [P37268-3] DR Ensembl; ENST00000528812.5; ENSP00000431749.1; ENSG00000079459.15. [P37268-2] DR Ensembl; ENST00000530337.6; ENSP00000431852.2; ENSG00000079459.15. [P37268-1] DR Ensembl; ENST00000530664.5; ENSP00000432331.1; ENSG00000079459.15. [P37268-2] DR Ensembl; ENST00000615631.5; ENSP00000481481.1; ENSG00000079459.15. [P37268-1] DR Ensembl; ENST00000622850.3; ENSP00000484122.1; ENSG00000079459.15. [P37268-2] DR Ensembl; ENST00000647069.3; ENSP00000495060.2; ENSG00000284967.3. [P37268-5] DR Ensembl; ENST00000647178.2; ENSP00000496723.1; ENSG00000284967.3. [P37268-1] DR Ensembl; ENST00000710773.1; ENSP00000518476.1; ENSG00000284967.3. [P37268-2] DR Ensembl; ENST00000710774.1; ENSP00000518477.1; ENSG00000284967.3. [P37268-1] DR Ensembl; ENST00000710775.1; ENSP00000518478.1; ENSG00000284967.3. [P37268-1] DR Ensembl; ENST00000710778.1; ENSP00000518480.1; ENSG00000284967.3. [P37268-3] DR Ensembl; ENST00000710780.1; ENSP00000518482.1; ENSG00000284967.3. [P37268-2] DR Ensembl; ENST00000710781.1; ENSP00000518483.1; ENSG00000284967.3. [P37268-2] DR Ensembl; ENST00000866105.1; ENSP00000536164.1; ENSG00000079459.15. [P37268-1] DR Ensembl; ENST00000866106.1; ENSP00000536165.1; ENSG00000079459.15. [P37268-1] DR Ensembl; ENST00000941571.1; ENSP00000611630.1; ENSG00000079459.15. [P37268-1] DR GeneID; 2222; -. DR KEGG; hsa:2222; -. DR MANE-Select; ENST00000220584.9; ENSP00000220584.4; NM_004462.5; NP_004453.3. DR UCSC; uc003wuh.4; human. [P37268-1] DR AGR; HGNC:3629; -. DR ClinPGx; PA28073; -. DR CTD; 2222; -. DR DisGeNET; 2222; -. DR GeneCards; FDFT1; -. DR GeneReviews; FDFT1; -. DR HGNC; HGNC:3629; FDFT1. DR HPA; ENSG00000079459; Low tissue specificity. DR MalaCards; FDFT1; -. DR MIM; 184420; gene. DR MIM; 618156; phenotype. DR OpenTargets; ENSG00000079459; -. DR VEuPathDB; HostDB:ENSG00000079459; -. DR eggNOG; KOG1459; Eukaryota. DR GeneTree; ENSGT00390000016034; -. DR HOGENOM; CLU_031981_0_2_1; -. DR InParanoid; P37268; -. DR OMA; GEACQLM; -. DR OrthoDB; 431150at2759; -. DR PAN-GO; P37268; 4 GO annotations based on evolutionary models. DR PhylomeDB; P37268; -. DR BioCyc; MetaCyc:HS01329-MONOMER; -. DR BRENDA; 2.5.1.21; 2681. DR PathwayCommons; P37268; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP). DR Reactome; R-HSA-9969896; Lanosterol biosynthesis. DR SABIO-RK; P37268; -. DR SignaLink; P37268; -. DR UniPathway; UPA00767; UER00751. DR Agora; ENSG00000079459; -. DR BioGRID-ORCS; 2222; 70 hits in 1157 CRISPR screens. DR ChiTaRS; FDFT1; human. DR EvolutionaryTrace; P37268; -. DR GenomeRNAi; 2222; -. DR Pharos; P37268; Tchem. DR PRO; PR:P37268; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; P37268; protein. DR Bgee; ENSG00000079459; Expressed in ganglionic eminence and 158 other cell types or tissues. DR ExpressionAtlas; P37268; baseline and differential. DR GO; GO:0098554; C:cytoplasmic side of endoplasmic reticulum membrane; IEA:Ensembl. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0051996; F:squalene synthase [NAD(P)H] activity; EXP:UniProtKB. DR GO; GO:0006695; P:cholesterol biosynthetic process; IBA:GO_Central. DR GO; GO:0033489; P:cholesterol biosynthetic process via desmosterol; IEA:Ensembl. DR GO; GO:0033490; P:cholesterol biosynthetic process via lathosterol; IEA:Ensembl. DR GO; GO:0045338; P:farnesyl diphosphate metabolic process; IBA:GO_Central. DR GO; GO:0006694; P:steroid biosynthetic process; TAS:ProtInc. DR GO; GO:0036197; P:zymosterol biosynthetic process; IEA:Ensembl. DR CDD; cd00683; Trans_IPPS_HH; 1. DR DisProt; DP03842; -. DR FunFam; 1.10.600.10:FF:000053; Squalene synthase; 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. DR PDBsum; 1EZF; -. DR PDBsum; 3ASX; -. DR PDBsum; 3LEE; -. DR PDBsum; 3Q2Z; -. DR PDBsum; 3Q30; -. DR PDBsum; 3V66; -. DR PDBsum; 3VJ8; -. DR PDBsum; 3VJ9; -. DR PDBsum; 3VJA; -. DR PDBsum; 3VJB; -. DR PDBsum; 3VJC; -. DR PDBsum; 3WC9; -. DR PDBsum; 3WCD; -. DR PDBsum; 3WCF; -. DR PDBsum; 3WCH; -. DR PDBsum; 3WCI; -. DR PDBsum; 3WCJ; -. DR PDBsum; 3WCL; -. DR PDBsum; 3WCM; -. DR PDBsum; 3WEF; -. DR PDBsum; 3WEG; -. DR PDBsum; 3WEH; -. DR PDBsum; 3WEI; -. DR PDBsum; 3WEJ; -. DR PDBsum; 3WEK; -. DR PDBsum; 3WSA; -. DR PDBsum; 6PYJ; -. DR PDBsum; 6PYV; -. DR PDBsum; 6PYW; -. DR PDBsum; 6PZ5; -. DR PDBsum; 8WTQ; -. DR PDBsum; 8WTR; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cholesterol biosynthesis; KW Cholesterol metabolism; Endoplasmic reticulum; Lipid biosynthesis; KW Lipid metabolism; Magnesium; Membrane; Metal-binding; KW Multifunctional enzyme; NAD; NADP; Proteomics identification; 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_0000067443" 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:0000305|PubMed:24531458" FT BINDING 77 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000305|PubMed:24531458" FT BINDING 80 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:24531458, FT ECO:0007744|PDB:3WEG, ECO:0007744|PDB:3WEH" FT BINDING 83 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:24531458, FT ECO:0007744|PDB:3WEG, ECO:0007744|PDB:3WEH" FT BINDING 84 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:24531458, FT ECO:0007744|PDB:3WEG, ECO:0007744|PDB:3WEH" FT BINDING 218 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000305|PubMed:24531458" FT BINDING 315 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000305|PubMed:24531458" FT BINDING 317 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000305|PubMed:24531458" FT VAR_SEQ 1..111 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056517" FT VAR_SEQ 1..85 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056282" FT VAR_SEQ 1..64 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056283" FT VAR_SEQ 128..170 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056518" FT VARIANT 45 FT /note="K -> R (influences plasma cholesterol levels; FT associated with increased total cholesterol and FT non-high-density lipoprotein cholesterol; dbSNP:rs4731)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:18350552" FT /id="VAR_011786" FT VARIANT 392 FT /note="L -> P (in dbSNP:rs1804473)" FT /id="VAR_011787" FT CONFLICT 353 FT /note="D -> N (in Ref. 4; AAB33404)" FT /evidence="ECO:0000305" FT CONFLICT 402 FT /note="T -> A (in Ref. 3; CAA48896)" FT /evidence="ECO:0000305" FT HELIX 35..37 FT /evidence="ECO:0007829|PDB:1EZF" FT HELIX 38..51 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 52..54 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 55..59 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 65..84 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 90..103 FT /evidence="ECO:0007829|PDB:3VJ8" FT TURN 117..119 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 120..123 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 125..134 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 137..156 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 157..159 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 160..162 FT /evidence="ECO:0007829|PDB:3ASX" FT HELIX 165..172 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 173..177 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 178..190 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 195..199 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 201..218 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 220..225 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 233..236 FT /evidence="ECO:0007829|PDB:3VJ8" FT TURN 237..239 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 243..247 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 249..251 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 252..267 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 270..278 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 283..303 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 307..310 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 313..315 FT /evidence="ECO:0007829|PDB:1EZF" FT HELIX 318..327 FT /evidence="ECO:0007829|PDB:3VJ8" FT STRAND 328..330 FT /evidence="ECO:0007829|PDB:3VJC" FT HELIX 331..346 FT /evidence="ECO:0007829|PDB:3VJ8" FT HELIX 356..368 FT /evidence="ECO:0007829|PDB:3VJ8" 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 //