FPS_DICDI
ID FPS_DICDI Reviewed; 382 AA.
AC Q9NH03; Q54XP0;
DT 20-APR-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Farnesyl diphosphate synthase;
DE Short=Dfps;
DE EC=2.5.1.10;
DE AltName: Full=(2E,6E)-farnesyl diphosphate synthase;
DE AltName: Full=Dimethylallyltranstransferase;
DE EC=2.5.1.1;
DE AltName: Full=Geranyltranstransferase;
GN Name=fps; ORFNames=DDB_G0278735;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=10804029; DOI=10.1359/jbmr.2000.15.5.971;
RA Grove J.E., Brown R.J., Watts D.J.;
RT "The intracellular target for the antiresorptive aminobisphosphonate drugs
RT in Dictyostelium discoideum is the enzyme farnesyl diphosphate synthase.";
RL J. Bone Miner. Res. 15:971-981(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [3]
RP ACTIVITY REGULATION.
RX PubMed=12086477; DOI=10.1021/jm010279+;
RA Szabo C.M., Martin M.B., Oldfield E.;
RT "An investigation of bone resorption and Dictyostelium discoideum growth
RT inhibition by bisphosphonate drugs.";
RL J. Med. Chem. 45:2894-2903(2002).
CC -!- FUNCTION: Key enzyme in isoprenoid biosynthesis which catalyzes the
CC formation of farnesyl diphosphate (FPP), a sterol precursor. Involved
CC in the inhibition of cell growth. {ECO:0000269|PubMed:10804029}.
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: Inhibited by aminobisphosphonate drugs (aBP), such
CC as risedronate and alendronate. {ECO:0000269|PubMed:10804029,
CC ECO:0000269|PubMed:12086477}.
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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; AF234168; AAF37872.1; -; mRNA.
DR EMBL; AAFI02000024; EAL67969.1; -; Genomic_DNA.
DR RefSeq; XP_641990.1; XM_636898.1.
DR AlphaFoldDB; Q9NH03; -.
DR SMR; Q9NH03; -.
DR STRING; 44689.DDB0215017; -.
DR PaxDb; Q9NH03; -.
DR EnsemblProtists; EAL67969; EAL67969; DDB_G0278735.
DR GeneID; 8621722; -.
DR KEGG; ddi:DDB_G0278735; -.
DR dictyBase; DDB_G0278735; fps.
DR eggNOG; KOG0711; Eukaryota.
DR HOGENOM; CLU_028376_0_1_1; -.
DR InParanoid; Q9NH03; -.
DR OMA; DENYGQK; -.
DR PhylomeDB; Q9NH03; -.
DR Reactome; R-DDI-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00259; UER00368.
DR UniPathway; UPA00260; UER00369.
DR PRO; PR:Q9NH03; -.
DR Proteomes; UP000002195; Chromosome 3.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005777; C:peroxisome; IDA:dictyBase.
DR GO; GO:0004161; F:dimethylallyltranstransferase activity; IBA:GO_Central.
DR GO; GO:0004337; F:geranyltranstransferase activity; ISS:dictyBase.
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; ISS:dictyBase.
DR GO; GO:0033384; P:geranyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:dictyBase.
DR CDD; cd00685; Trans_IPPS_HT; 1.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR039702; FPS1-like.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR000092; Polyprenyl_synt.
DR InterPro; IPR033749; Polyprenyl_synt_CS.
DR PANTHER; PTHR11525; PTHR11525; 1.
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 Cholesterol biosynthesis; Cholesterol metabolism; Cytoplasm;
KW Isoprene biosynthesis; Lipid biosynthesis; Lipid metabolism; Magnesium;
KW Metal-binding; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase.
FT CHAIN 1..382
FT /note="Farnesyl diphosphate synthase"
FT /id="PRO_0000393337"
FT BINDING 81
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 84
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 120
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 127
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 127
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 131
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 131
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 136
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT BINDING 137
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 230
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT BINDING 231
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT BINDING 270
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT BINDING 287
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT BINDING 296
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
SQ SEQUENCE 382 AA; 43590 MW; C9169F1B40014D5E CRC64;
MNNQSLQRAA MISEHLAPTS ELNMNQTSAP IKTAKEELAD FVEIFPILTN EILKELPGMD
MPPQTIAWVE KMINVNVSGG KMNRGLTVLH SLQLLVEGRQ LSRSEIFLAN VLGWCVEWLQ
AFFLVADDIM DQSITRRGQP CWYRQANPIS NNGTIGSIAI NDSFILESCI YILIKKYFRN
EPYYADILDI FHETSYQTEL GQLLDLTTQP NRGDFSLFTL NTYRRIVKYK TAYYSFYLPV
ALAMLMAGIT STPAFSTAKD ILLPMGEFFQ VQDDFLDCYG SPAVIGKIGR DIEENKCSWM
ICQAILNGTP EQINLLKKHY GLDNPTDVEL VKKIYGEIGL KKIFKDYEDE SYAFLISKIK
SVRIMPQEVF IKLLSKIYKR DL
