FDFT_HUMAN
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 03-AUG-2022, entry version 218.
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 + 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: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 + 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: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 = diphosphate + presqualene
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=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: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=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: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; A0A024R644: CLN5; NbExp=3; IntAct=EBI-714550, EBI-12838990;
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; 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}.
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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_001287742.1. [P37268-1]
DR RefSeq; NP_001274672.1; NM_001287743.1. [P37268-1]
DR RefSeq; NP_001274673.1; NM_001287744.1. [P37268-2]
DR RefSeq; NP_001274674.1; NM_001287745.1. [P37268-2]
DR RefSeq; NP_001274676.1; NM_001287747.1. [P37268-2]
DR RefSeq; NP_001274677.1; NM_001287748.1. [P37268-2]
DR RefSeq; NP_001274678.1; NM_001287749.1. [P37268-2]
DR RefSeq; NP_001274679.1; NM_001287750.1.
DR RefSeq; NP_001274680.1; NM_001287751.1. [P37268-3]
DR RefSeq; NP_001274685.1; NM_001287756.1.
DR RefSeq; NP_004453.3; NM_004462.4. [P37268-1]
DR RefSeq; XP_016868706.1; XM_017013217.1.
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 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 AlphaFoldDB; P37268; -.
DR SMR; P37268; -.
DR BioGRID; 108516; 131.
DR IntAct; P37268; 51.
DR MINT; P37268; -.
DR STRING; 9606.ENSP00000480828; -.
DR BindingDB; P37268; -.
DR ChEMBL; CHEMBL3338; -.
DR DrugBank; DB05317; TAK-475.
DR DrugCentral; P37268; -.
DR GuidetoPHARMACOLOGY; 645; -.
DR SwissLipids; SLP:000000138; -.
DR iPTMnet; P37268; -.
DR MetOSite; P37268; -.
DR PhosphoSitePlus; P37268; -.
DR SwissPalm; P37268; -.
DR BioMuta; FDFT1; -.
DR DMDM; 585126; -.
DR EPD; P37268; -.
DR jPOST; P37268; -.
DR MassIVE; P37268; -.
DR MaxQB; P37268; -.
DR PaxDb; P37268; -.
DR PeptideAtlas; P37268; -.
DR PRIDE; P37268; -.
DR ProteomicsDB; 3554; -.
DR ProteomicsDB; 4370; -.
DR ProteomicsDB; 5075; -.
DR ProteomicsDB; 55271; -. [P37268-1]
DR ProteomicsDB; 6339; -.
DR Antibodypedia; 1355; 453 antibodies from 32 providers.
DR DNASU; 2222; -.
DR Ensembl; ENST00000220584.9; ENSP00000220584.4; ENSG00000079459.13. [P37268-1]
DR Ensembl; ENST00000443614.6; ENSP00000390367.2; ENSG00000079459.13. [P37268-5]
DR Ensembl; ENST00000525777.5; ENSP00000436069.1; ENSG00000079459.13. [P37268-3]
DR Ensembl; ENST00000528643.5; ENSP00000431649.1; ENSG00000079459.13. [P37268-3]
DR Ensembl; ENST00000528812.5; ENSP00000431749.1; ENSG00000079459.13. [P37268-2]
DR Ensembl; ENST00000530664.5; ENSP00000432331.1; ENSG00000079459.13. [P37268-2]
DR Ensembl; ENST00000538689.4; ENSP00000444248.2; ENSG00000079459.13. [P37268-2]
DR Ensembl; ENST00000615631.4; ENSP00000481481.1; ENSG00000079459.13. [P37268-1]
DR Ensembl; ENST00000618539.4; ENSP00000480828.1; ENSG00000079459.13. [P37268-1]
DR Ensembl; ENST00000622850.2; ENSP00000484122.1; ENSG00000079459.13. [P37268-2]
DR Ensembl; ENST00000623368.3; ENSP00000485229.1; ENSG00000079459.13. [P37268-2]
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 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 neXtProt; NX_P37268; -.
DR OpenTargets; ENSG00000079459; -.
DR PharmGKB; PA28073; -.
DR VEuPathDB; HostDB:ENSG00000079459; -.
DR eggNOG; KOG1459; Eukaryota.
DR GeneTree; ENSGT00390000016034; -.
DR HOGENOM; CLU_031981_0_2_1; -.
DR InParanoid; P37268; -.
DR OMA; RFWPKEI; -.
DR OrthoDB; 563702at2759; -.
DR PhylomeDB; P37268; -.
DR TreeFam; TF105316; -.
DR BioCyc; MetaCyc:HS01329-MON; -.
DR BRENDA; 2.5.1.21; 2681.
DR PathwayCommons; P37268; -.
DR Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP).
DR SABIO-RK; P37268; -.
DR SignaLink; P37268; -.
DR UniPathway; UPA00767; UER00751.
DR BioGRID-ORCS; 2222; 69 hits in 1077 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 156 other tissues.
DR ExpressionAtlas; P37268; baseline and differential.
DR Genevisible; P37268; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0004310; F:farnesyl-diphosphate farnesyltransferase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051996; F:squalene synthase activity; IBA:GO_Central.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0045338; P:farnesyl diphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; TAS:ProtInc.
DR CDD; cd00683; Trans_IPPS_HH; 1.
DR Gene3D; 1.10.600.10; -; 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 PANTHER; PTHR11626; PTHR11626; 1.
DR Pfam; PF00494; SQS_PSY; 1.
DR SFLD; SFLDG01018; Squalene/Phytoene_Synthase_Lik; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
DR TIGRFAMs; TIGR01559; squal_synth; 1.
DR PROSITE; PS01044; SQUALEN_PHYTOEN_SYN_1; 1.
DR PROSITE; PS01045; SQUALEN_PHYTOEN_SYN_2; 1.
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; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transferase; Transmembrane; 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 non-high-
FT 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 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 165..175
FT /evidence="ECO:0007829|PDB:3VJ8"
FT HELIX 177..189
FT /evidence="ECO:0007829|PDB:3VJ8"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:3WEK"
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 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
