FDFT_MOUSE
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 03-AUG-2022, entry version 167.
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; 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 + 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:10521476};
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 -!- 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_034321.2; NM_010191.3.
DR RefSeq; XP_017171333.1; XM_017315844.1.
DR AlphaFoldDB; P53798; -.
DR SMR; P53798; -.
DR STRING; 10090.ENSMUSP00000055313; -.
DR ChEMBL; CHEMBL4778; -.
DR iPTMnet; P53798; -.
DR PhosphoSitePlus; P53798; -.
DR SwissPalm; P53798; -.
DR EPD; P53798; -.
DR jPOST; P53798; -.
DR MaxQB; P53798; -.
DR PaxDb; P53798; -.
DR PeptideAtlas; P53798; -.
DR PRIDE; P53798; -.
DR ProteomicsDB; 267725; -.
DR Antibodypedia; 1355; 453 antibodies from 32 providers.
DR DNASU; 14137; -.
DR Ensembl; ENSMUST00000054963; ENSMUSP00000055313; ENSMUSG00000021273.
DR Ensembl; ENSMUST00000224625; ENSMUSP00000153671; ENSMUSG00000021273.
DR GeneID; 14137; -.
DR KEGG; mmu:14137; -.
DR UCSC; uc007uhj.3; mouse.
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; RFWPKEI; -.
DR OrthoDB; 563702at2759; -.
DR PhylomeDB; P53798; -.
DR TreeFam; TF105316; -.
DR Reactome; R-MMU-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00767; UER00751.
DR BioGRID-ORCS; 14137; 6 hits in 61 CRISPR screens.
DR ChiTaRS; Fdft1; mouse.
DR PRO; PR:P53798; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P53798; protein.
DR Bgee; ENSMUSG00000021273; Expressed in primary oocyte and 128 other tissues.
DR ExpressionAtlas; P53798; baseline and differential.
DR Genevisible; P53798; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0004310; F:farnesyl-diphosphate farnesyltransferase activity; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0045338; P:farnesyl diphosphate metabolic process; ISO:MGI.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:UniProtKB-KW.
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 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
