FDFT_BOVIN
ID FDFT_BOVIN Reviewed; 417 AA.
AC Q32KR6;
DT 12-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Squalene synthase;
DE Short=SQS;
DE Short=SS;
DE EC=2.5.1.21 {ECO:0000250|UniProtKB:P37268};
DE AltName: Full=FPP:FPP farnesyltransferase;
DE AltName: Full=Farnesyl-diphosphate farnesyltransferase;
GN Name=FDFT1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
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:0000250|UniProtKB:P37268}.
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:0000250|UniProtKB:P37268};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32296;
CC Evidence={ECO:0000250|UniProtKB:P37268};
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 Evidence={ECO:0000250|UniProtKB:P37268};
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 -!- SIMILARITY: Belongs to the phytoene/squalene synthase family.
CC {ECO:0000305}.
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DR EMBL; BC109959; AAI09960.1; -; mRNA.
DR AlphaFoldDB; Q32KR6; -.
DR SMR; Q32KR6; -.
DR STRING; 9913.ENSBTAP00000016504; -.
DR PaxDb; Q32KR6; -.
DR PRIDE; Q32KR6; -.
DR eggNOG; KOG1459; Eukaryota.
DR InParanoid; Q32KR6; -.
DR OrthoDB; 563702at2759; -.
DR UniPathway; UPA00767; UER00751.
DR Proteomes; UP000009136; Unplaced.
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: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: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 2: Evidence at transcript 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..417
FT /note="Squalene synthase"
FT /id="PRO_0000290005"
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"
SQ SEQUENCE 417 AA; 48304 MW; C6A2FD8EA5C85BC7 CRC64;
MEFVKCLGHP EEFYNLLRFQ MGGRRKVIPK MDQDSLSSSL KTCYKYLNQT SRSFAAVIQA
LDGEMRHAVC IFYLVLRALD TLEDDMTISI ERKVPLLHNF HSYLYEPDWR FTESKEKDRQ
VLEDFPTISL EFRNLAEKYQ TVIVDVCQKM GFGMAEFLDK RVTSEREWDK YCHYVAGLVG
IGLSRLFPAS ELEDPLIGED TERANSMGLF LQKTNIIRDY LEDQREGREF WPQETWSKYV
KKLGDFAKPE NIDLAVQCLN ELITNTLHHI PDVITYLSRL RNQSIFNFCA IPQVMAIATL
AACYNNQQVF KGVVKIRKGQ AVTLMMDATN MPAVKAIIHQ YMEEIYHRIP NSDPCSTKTQ
QIISTIRTQN LPNCQLVSRS HYSPIYLSFV MLLAALSWQY LSTLSQVTED YVQTGEH
