FPPS_MOUSE
ID FPPS_MOUSE Reviewed; 353 AA.
AC Q920E5;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 159.
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 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].
RX PubMed=12020352; DOI=10.1042/bj20020560;
RA Reilly J.F., Martinez S.D., Mickey G., Maher P.A.;
RT "A novel role for farnesyl pyrophosphate synthase in fibroblast growth
RT factor-mediated signal transduction.";
RL Biochem. J. 366:501-510(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Thymus;
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 MRNA].
RC TISSUE=Brain;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, 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: 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 {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF309508; AAL09445.1; -; mRNA.
DR EMBL; AK088601; BAC40446.1; -; mRNA.
DR EMBL; BC048497; AAH48497.1; -; mRNA.
DR CCDS; CCDS17488.1; -.
DR RefSeq; NP_001240680.1; NM_001253751.1.
DR RefSeq; NP_608219.1; NM_134469.4.
DR AlphaFoldDB; Q920E5; -.
DR SMR; Q920E5; -.
DR BioGRID; 225377; 15.
DR STRING; 10090.ENSMUSP00000080531; -.
DR BindingDB; Q920E5; -.
DR ChEMBL; CHEMBL4523414; -.
DR iPTMnet; Q920E5; -.
DR PhosphoSitePlus; Q920E5; -.
DR SwissPalm; Q920E5; -.
DR EPD; Q920E5; -.
DR jPOST; Q920E5; -.
DR MaxQB; Q920E5; -.
DR PaxDb; Q920E5; -.
DR PRIDE; Q920E5; -.
DR ProteomicsDB; 271603; -.
DR TopDownProteomics; Q920E5; -.
DR Antibodypedia; 34190; 457 antibodies from 36 providers.
DR DNASU; 110196; -.
DR Ensembl; ENSMUST00000081848; ENSMUSP00000080531; ENSMUSG00000059743.
DR Ensembl; ENSMUST00000196709; ENSMUSP00000142770; ENSMUSG00000059743.
DR GeneID; 110196; -.
DR KEGG; mmu:110196; -.
DR UCSC; uc008pxo.2; mouse.
DR CTD; 2224; -.
DR MGI; MGI:104888; Fdps.
DR VEuPathDB; HostDB:ENSMUSG00000059743; -.
DR eggNOG; KOG0711; Eukaryota.
DR GeneTree; ENSGT00900000141074; -.
DR InParanoid; Q920E5; -.
DR OMA; DENYGQK; -.
DR OrthoDB; 1066656at2759; -.
DR PhylomeDB; Q920E5; -.
DR TreeFam; TF300897; -.
DR Reactome; R-MMU-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00259; UER00368.
DR UniPathway; UPA00260; UER00369.
DR BioGRID-ORCS; 110196; 15 hits in 54 CRISPR screens.
DR ChiTaRS; Fdps; mouse.
DR PRO; PR:Q920E5; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q920E5; protein.
DR Bgee; ENSMUSG00000059743; Expressed in midbrain and 142 other tissues.
DR ExpressionAtlas; Q920E5; baseline and differential.
DR Genevisible; Q920E5; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005777; C:peroxisome; ISO:MGI.
DR GO; GO:0004161; F:dimethylallyltranstransferase activity; IBA:GO_Central.
DR GO; GO:0004337; F:geranyltranstransferase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0045337; P:farnesyl diphosphate biosynthetic process; ISO:MGI.
DR GO; GO:0033384; P:geranyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; ISO:MGI.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; ISO:MGI.
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 1: Evidence at protein 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_0000123945"
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"
SQ SEQUENCE 353 AA; 40582 MW; 9A3D7034ACAB576A CRC64;
MNGNQKLDAY NQEKQNFIQH FSQIVKVLTE KELGHPEIGD AIARLKEVLE YNALGGKYNR
GLTVVQAFQE LVEPKKQDAE SLQRALTVGW CVELLQAFFL VSDDIMDSSL TRRGQICWYQ
KPGIGLDAIN DALLLEASIY RLLKFYCREQ PYYLNLLELF LQSSYQTEIG QTLDLMTAPQ
GHVDLGRYTE KRYKSIVKYK TAFYSFYLPI AAAMYMAGID GEKEHANALK ILMEMGEFFQ
VQDDYLDLFG DPSVTGKVGT DIQDNKCSWL VVQCLLRASP QQRQILEENY GQKDPEKVAR
VKALYEALDL QSAFFKYEED SYNRLKSLIE QCSAPLPPSI FMELANKIYK RRK
