ID   FDFT_MOUSE              Reviewed;         416 AA.
AC   P53798; Q8BPF5;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   04-NOV-2026, entry version 187.
DE   RecName: Full=Squalene synthase;
DE            Short=SQS;
DE            Short=SS;
DE            EC=2.5.1.21 {ECO:0000269|PubMed:10521476};
DE   AltName: Full=FPP:FPP farnesyltransferase;
DE   AltName: Full=Farnesyl-diphosphate farnesyltransferase;
GN   Name=Fdft1; Synonyms=Erg9;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX   PubMed=7999794; DOI=10.1016/0167-4781(94)00178-6;
RA   Inoue T., Osumi T., Hata S.;
RT   "Molecular cloning and functional expression of a cDNA for mouse squalene
RT   synthase.";
RL   Biochim. Biophys. Acta 1260:49-54(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J;
RC   TISSUE=Amnion, Embryo, Heart, Kidney, and Visual cortex;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [5]
RP   DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND FUNCTION.
RX   PubMed=10521476; DOI=10.1074/jbc.274.43.30843;
RA   Tozawa R., Ishibashi S., Osuga J., Yagyu H., Oka T., Chen Z., Ohashi K.,
RA   Perrey S., Shionoiri F., Yahagi N., Harada K., Gotoda T., Yazaki Y.,
RA   Yamada N.;
RT   "Embryonic lethality and defective neural tube closure in mice lacking
RT   squalene synthase.";
RL   J. Biol. Chem. 274:30843-30848(1999).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Catalyzes the condensation of 2 farnesyl pyrophosphate (FPP)
CC       moieties to form squalene (PubMed:10521476). Proceeds in two distinct
CC       steps. In the first half-reaction, two molecules of FPP react to form
CC       the stable presqualene diphosphate intermediate (PSQPP), with
CC       concomitant release of a proton and a molecule of inorganic
CC       diphosphate. In the second half-reaction, PSQPP undergoes heterolysis,
CC       isomerization, and reduction with NADPH or NADH to form squalene. It is
CC       the first committed enzyme of the sterol biosynthesis pathway (By
CC       similarity). {ECO:0000250|UniProtKB:P37268,
CC       ECO:0000269|PubMed:10521476}.
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:10521476};
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:0000250|UniProtKB:P37268};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32300;
CC         Evidence={ECO:0000250|UniProtKB:P37268};
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:0000250|UniProtKB:P37268};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22229;
CC         Evidence={ECO:0000250|UniProtKB:P37268};
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: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 = presqualene diphosphate +
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   -!- 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   -!- DISRUPTION PHENOTYPE: Deficient mice are embryonic lethal around
CC       midgestation (9.5-10.5 dpc). Embryos exhibit severe growth retardation
CC       and defective neural tube closure. {ECO:0000269|PubMed:10521476}.
CC   -!- SIMILARITY: Belongs to the phytoene/squalene synthase family.
CC       {ECO:0000305}.
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DR   EMBL; D29016; BAA06102.1; -; mRNA.
DR   EMBL; AK076062; BAC36156.1; -; mRNA.
DR   EMBL; AK146766; BAE27418.1; -; mRNA.
DR   EMBL; AK158633; BAE34590.1; -; mRNA.
DR   EMBL; AK168629; BAE40489.1; -; mRNA.
DR   EMBL; AK169317; BAE41072.1; -; mRNA.
DR   EMBL; CH466535; EDL36069.1; -; Genomic_DNA.
DR   EMBL; BC054722; AAH54722.1; -; mRNA.
DR   EMBL; BC138301; AAI38302.1; -; mRNA.
DR   EMBL; BC138302; AAI38303.1; -; mRNA.
DR   CCDS; CCDS27198.1; -.
DR   PIR; S52075; S52075.
DR   RefSeq; NP_001347140.1; NM_001360211.2.
DR   RefSeq; NP_034321.2; NM_010191.4.
DR   RefSeq; XP_017171333.1; XM_017315844.1.
DR   AlphaFoldDB; P53798; -.
DR   SMR; P53798; -.
DR   BioGRID; 199625; 1.
DR   FunCoup; P53798; 1577.
DR   STRING; 10090.ENSMUSP00000153671; -.
DR   ChEMBL; CHEMBL4778; -.
DR   iPTMnet; P53798; -.
DR   PhosphoSitePlus; P53798; -.
DR   SwissPalm; P53798; -.
DR   jPOST; P53798; -.
DR   PaxDb; 10090-ENSMUSP00000153671; -.
DR   PeptideAtlas; P53798; -.
DR   ProteomicsDB; 267725; -.
DR   Pumba; P53798; -.
DR   Antibodypedia; 1355; 497 antibodies from 36 providers.
DR   DNASU; 14137; -.
DR   Ensembl; ENSMPUT00000001847; ENSMPUP00000001811; ENSMPUG00000001829.
DR   Ensembl; ENSMUST00000054963.10; ENSMUSP00000055313.10; ENSMUSG00000021273.12.
DR   Ensembl; ENSMUST00000224625.2; ENSMUSP00000153671.2; ENSMUSG00000021273.12.
DR   GeneID; 14137; -.
DR   KEGG; mmu:14137; -.
DR   UCSC; uc007uhj.3; mouse.
DR   AGR; MGI:102706; -.
DR   CTD; 2222; -.
DR   MGI; MGI:102706; Fdft1.
DR   VEuPathDB; HostDB:ENSMUSG00000021273; -.
DR   eggNOG; KOG1459; Eukaryota.
DR   GeneTree; ENSGT00390000016034; -.
DR   HOGENOM; CLU_031981_0_2_1; -.
DR   InParanoid; P53798; -.
DR   OMA; AACFQYL; -.
DR   OrthoDB; 24463at9989; -.
DR   PhylomeDB; P53798; -.
DR   Reactome; R-MMU-9969896; Lanosterol biosynthesis.
DR   UniPathway; UPA00767; UER00751.
DR   BioGRID-ORCS; 14137; 6 hits in 64 CRISPR screens.
DR   PRO; PR:P53798; -.
DR   Proteomes; UP000000589; Chromosome 14.
DR   RNAct; P53798; protein.
DR   Bgee; ENSMUSG00000021273; Expressed in primary oocyte and 131 other cell types or tissues.
DR   ExpressionAtlas; P53798; baseline and differential.
DR   GO; GO:0098554; C:cytoplasmic side of endoplasmic reticulum membrane; IDA:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:GO_Central.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0051996; F:squalene synthase [NAD(P)H] activity; IMP:MGI.
DR   GO; GO:0006695; P:cholesterol biosynthetic process; IMP:MGI.
DR   GO; GO:0045338; P:farnesyl diphosphate metabolic process; ISO:GO_Central.
DR   GO; GO:0036197; P:zymosterol biosynthetic process; IMP:MGI.
DR   CDD; cd00683; Trans_IPPS_HH; 1.
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.
PE   1: Evidence at protein 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..416
FT                   /note="Squalene synthase"
FT                   /id="PRO_0000067444"
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"
FT   CONFLICT        149
FT                   /note="R -> Q (in Ref. 1; BAA06102)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   416 AA;  48154 MW;  12C63625DD4FF92B CRC64;
     MEFVKCLGHP EEFYNLLRFR MGGRRNFIPK MDQDSLSSSL KTCYKYLNQT SRSFAAVIQA
     LDGDIRHAIC VFYLVLRALD TVEDDMSISV EKKIPLLCNF HTFLYDPEWR FTESKEKDRQ
     VLEDFPTISL EFRNLAEKYQ TVIDDICHRM GCGMAEFVDK DVTSKQDWDK YCHYVAGLVG
     IGLSRLFSAS EFEDPIVGED IECANSMGLF LQKTNIIRDY LEDQQEGRKF WPQEVWGRYI
     KKLEDFAKPE NVDVAVQCLN ELITNTLQHI PDVLTYLSRL RNQSVFNFCA IPQVMAIATL
     AACYNNQQVF KGVVKIRKGQ AVTLMMDATN MPAVKAIIYQ YIEEIYHRIP NSDPSSSKTK
     QVISKIRTQN LPNCQLISRS HYSPIYLSFI MLLAALSWQY LSTLSQVTED YVQREH
//