FPPS_RAT
ID FPPS_RAT Reviewed; 353 AA.
AC P05369; Q6GT82;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Farnesyl pyrophosphate synthase;
DE Short=FPP synthase;
DE Short=FPS;
DE EC=2.5.1.10;
DE AltName: Full=(2E,6E)-farnesyl diphosphate synthase;
DE AltName: Full=Cholesterol-regulated 39 kDa protein;
DE Short=CR 39;
DE AltName: Full=Dimethylallyltranstransferase;
DE EC=2.5.1.1;
DE AltName: Full=Farnesyl diphosphate synthase;
DE AltName: Full=Geranyltranstransferase;
GN Name=Fdps;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=3670308; DOI=10.1128/mcb.7.9.3138-3146.1987;
RA Clarke C.F., Tanaka R.D., Svenson K., Wamsley M., Fogelman A.M.,
RA Edwards P.A.;
RT "Molecular cloning and sequence of a cholesterol-repressible enzyme related
RT to prenyltransferase in the isoprene biosynthetic pathway.";
RL Mol. Cell. Biol. 7:3138-3146(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SEQUENCE REVISION.
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=2325654; DOI=10.1128/mcb.10.5.2315-2326.1990;
RA Teruya J.H., Kutsunai S.Y., Spear D.H., Edwards P.A., Clarke C.F.;
RT "Testis-specific transcription initiation sites of rat farnesyl
RT pyrophosphate synthetase mRNA.";
RL Mol. Cell. Biol. 10:2315-2326(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT HIS-110.
RC TISSUE=Pituitary;
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).
CC -!- FUNCTION: Key enzyme in isoprenoid biosynthesis which catalyzes the
CC formation of farnesyl diphosphate (FPP), a precursor for several
CC classes of essential metabolites including sterols, dolichols,
CC carotenoids, and ubiquinones. FPP also serves as substrate for protein
CC farnesylation and geranylgeranylation. Catalyzes the sequential
CC condensation of isopentenyl pyrophosphate with the allylic
CC pyrophosphates, dimethylallyl pyrophosphate, and then with the
CC resultant geranylpyrophosphate to the ultimate product farnesyl
CC pyrophosphate (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + isopentenyl diphosphate = (2E)-
CC geranyl diphosphate + diphosphate; Xref=Rhea:RHEA:22408,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:58057,
CC ChEBI:CHEBI:128769; EC=2.5.1.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-geranyl diphosphate + isopentenyl diphosphate = (2E,6E)-
CC farnesyl diphosphate + diphosphate; Xref=Rhea:RHEA:19361,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769,
CC ChEBI:CHEBI:175763; EC=2.5.1.10;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inactivated by interferon-induced RSAD2. This
CC inactivation may result of disruption of lipid rafts at the plasma
CC membrane, and thus have an antiviral effect since many enveloped
CC viruses need lipid rafts to bud efficiently out of the cell (By
CC similarity). {ECO:0000250}.
CC -!- PATHWAY: Isoprenoid biosynthesis; farnesyl diphosphate biosynthesis;
CC farnesyl diphosphate from geranyl diphosphate and isopentenyl
CC diphosphate: step 1/1.
CC -!- PATHWAY: Isoprenoid biosynthesis; geranyl diphosphate biosynthesis;
CC geranyl diphosphate from dimethylallyl diphosphate and isopentenyl
CC diphosphate: step 1/1.
CC -!- SUBUNIT: Homodimer. Interacts with RSAD2 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Testis, liver, kidney, brain and adrenal gland.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; M34477; AAA41143.1; -; mRNA.
DR EMBL; M17300; AAA40960.1; ALT_SEQ; mRNA.
DR EMBL; BC059125; AAH59125.1; -; mRNA.
DR PIR; A34713; A34713.
DR PIR; B34713; B34713.
DR RefSeq; NP_114028.1; NM_031840.1.
DR AlphaFoldDB; P05369; -.
DR SMR; P05369; -.
DR BioGRID; 249834; 1.
DR IntAct; P05369; 1.
DR BindingDB; P05369; -.
DR ChEMBL; CHEMBL1075093; -.
DR DrugCentral; P05369; -.
DR GuidetoPHARMACOLOGY; 644; -.
DR iPTMnet; P05369; -.
DR PhosphoSitePlus; P05369; -.
DR jPOST; P05369; -.
DR PRIDE; P05369; -.
DR GeneID; 83791; -.
DR KEGG; rno:83791; -.
DR UCSC; RGD:68953; rat.
DR CTD; 2224; -.
DR RGD; 68953; Fdps.
DR InParanoid; P05369; -.
DR OrthoDB; 1066656at2759; -.
DR PhylomeDB; P05369; -.
DR Reactome; R-RNO-191273; Cholesterol biosynthesis.
DR SABIO-RK; P05369; -.
DR UniPathway; UPA00259; UER00368.
DR UniPathway; UPA00260; UER00369.
DR PRO; PR:P05369; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:RGD.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0004161; F:dimethylallyltranstransferase activity; IBA:GO_Central.
DR GO; GO:0004337; F:geranyltranstransferase activity; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0071398; P:cellular response to fatty acid; IEP:RGD.
DR GO; GO:0006695; P:cholesterol biosynthetic process; TAS:RGD.
DR GO; GO:0045337; P:farnesyl diphosphate biosynthetic process; IDA:RGD.
DR GO; GO:0033384; P:geranyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; IMP:RGD.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; IMP:RGD.
DR GO; GO:0070723; P:response to cholesterol; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR CDD; cd00685; Trans_IPPS_HT; 1.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR000092; Polyprenyl_synt.
DR InterPro; IPR033749; Polyprenyl_synt_CS.
DR Pfam; PF00348; polyprenyl_synt; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
DR PROSITE; PS00723; POLYPRENYL_SYNTHASE_1; 1.
DR PROSITE; PS00444; POLYPRENYL_SYNTHASE_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cholesterol biosynthesis; Cholesterol metabolism; Cytoplasm;
KW Hydroxylation; Isoprene biosynthesis; Lipid biosynthesis; Lipid metabolism;
KW Magnesium; Metal-binding; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase.
FT CHAIN 1..353
FT /note="Farnesyl pyrophosphate synthase"
FT /id="PRO_0000123946"
FT BINDING 57
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 60
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 96
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 103
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 103
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 107
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 107
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 112
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT BINDING 113
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 200
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT BINDING 201
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT BINDING 240
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT BINDING 257
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT BINDING 266
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT SITE 98
FT /note="Important for determining product chain length"
FT /evidence="ECO:0000250"
FT SITE 99
FT /note="Important for determining product chain length"
FT /evidence="ECO:0000250"
FT MOD_RES 57
FT /note="N6-(2-hydroxyisobutyryl)lysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT MOD_RES 57
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT VARIANT 110
FT /note="Y -> H"
FT /evidence="ECO:0000269|PubMed:15489334"
SQ SEQUENCE 353 AA; 40830 MW; 27FD7E0DD6FEA001 CRC64;
MNGDQKLDVH NQEKQNFIQH FSQIVKVLTE DELGHPEKGD AITRIKEVLE YNTVGGKYNR
GLTVVQTFQE LVEPRKQDAE SLQRALTVGW CVELLQAFFL VLDDIMDSSY TRRGQICWYQ
KPGIGLDAIN DALLLEAAIY RLLKFYCREQ PYYLNLLELF LQSSYQTEIG QTLDLITAPQ
GQVDLGRYTE KRYKSIVKYK TAFYSFYLPI AAAMYMAGID GEKEHANALK ILLEMGEFFQ
IQDDYLDLFG DPSVTGKVGT DIQDNKCSWL VVQCLLRATP QQRQILEENY GQKDPEKVAR
VKALYEELDL RSVFFKYEED SYNRLKSLIE QCSAPLPPSI FLELANKIYK RRK
