FPPS_ARTAN
ID FPPS_ARTAN Reviewed; 343 AA.
AC P49350; A0A2U1Q7M0; E2D028; Q9SYX3; Q9ZPJ3;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2019, sequence version 2.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Farnesyl pyrophosphate synthase;
DE Short=FPP synthase {ECO:0000303|PubMed:8682304};
DE Short=FPS {ECO:0000303|PubMed:8682304};
DE EC=2.5.1.10 {ECO:0000269|PubMed:8682304, ECO:0000269|Ref.7};
DE AltName: Full=(2E,6E)-farnesyl diphosphate synthase {ECO:0000303|PubMed:10814821};
DE AltName: Full=Dimethylallyltranstransferase;
DE EC=2.5.1.1 {ECO:0000269|PubMed:8682304};
DE AltName: Full=Farnesyl diphosphate synthase {ECO:0000303|PubMed:8682304};
DE AltName: Full=Geranyltranstransferase;
GN Name=FPS1 {ECO:0000303|PubMed:8682304};
GN Synonyms=FDS {ECO:0000303|PubMed:10814821},
GN FPPS {ECO:0000303|PubMed:19664791};
GN ORFNames=CTI12_AA043570 {ECO:0000312|EMBL:PWA94011.1};
OS Artemisia annua (Sweet wormwood).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Asterales; Asteraceae; Asteroideae; Anthemideae;
OC Artemisiinae; Artemisia.
OX NCBI_TaxID=35608;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=8682304; DOI=10.1016/0378-1119(96)00054-6;
RA Matsushita Y., Kang W., Charlwood B.V.;
RT "Cloning and analysis of a cDNA encoding farnesyl diphosphate synthase from
RT Artemisia annua.";
RL Gene 172:207-209(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Chen D., Ye H.C., Li G.F.;
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=10814821; DOI=10.1016/s0168-9452(00)00217-x;
RA Chen D.-H., Ye H.-C., Li G.-F.;
RT "Expression of a chimeric farnesyl diphosphate synthase gene in Artemisia
RT annua L. transgenic plants via Agrobacterium tumefaciens-mediated
RT transformation.";
RL Plant Sci. 155:179-185(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Banyai W., Supaibulwatana K.;
RL Submitted (JUL-2009) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Sankhuan D., Chowpongpang S., Kirdmanee C., Supaibulwatana K.;
RT "Molecular cloning of farnesyl pyrophosphate synthase (FPS).";
RL Submitted (MAR-2014) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Huhao1; TISSUE=Leaf;
RX PubMed=29703587; DOI=10.1016/j.molp.2018.03.015;
RA Shen Q., Zhang L., Liao Z., Wang S., Yan T., Shi P., Liu M., Fu X., Pan Q.,
RA Wang Y., Lv Z., Lu X., Zhang F., Jiang W., Ma Y., Chen M., Hao X., Li L.,
RA Tang Y., Lv G., Zhou Y., Sun X., Brodelius P.E., Rose J.K.C., Tang K.;
RT "The genome of Artemisia annua provides insight into the evolution of
RT Asteraceae family and artemisinin biosynthesis.";
RL Mol. Plant 11:776-788(2018).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOTECHNOLOGY, AND PATHWAY.
RX DOI=10.1111/j.1744-7909.2006.00208.x;
RA Han J.-L., Liu B.-Y., Ye H.-C., Wang H., Li Z.-Q., Li G.-F.;
RT "Effects of overexpression of the endogenous farnesyl diphosphate synthase
RT on the artemisinin content in Artemisia annua L.";
RL J. Integr. Plant Biol. 48:482-487(2006).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=19664791; DOI=10.1016/j.phytochem.2009.07.009;
RA Olsson M.E., Olofsson L.M., Lindahl A.-L., Lundgren A., Brodelius M.,
RA Brodelius P.E.;
RT "Localization of enzymes of artemisinin biosynthesis to the apical cells of
RT glandular secretory trichomes of Artemisia annua L.";
RL Phytochemistry 70:1123-1128(2009).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, AND BIOTECHNOLOGY.
RX DOI=10.1007/s11240-010-9775-8;
RA Banyai W., Kirdmanee C., Mii M., Supaibulwatana K.;
RT "Overexpression of farnesyl pyrophosphate synthase (FPS) gene affected
RT artemisinin content and growth of Artemisia annua L.";
RL Plant Cell Tissue Organ Cult. 103:255-265(2010).
RN [10]
RP INDUCTION BY GIBBERELLIC ACID.
RX DOI=10.1007/s10725-010-9510-9;
RA Banyai W., Mii M., Supaibulwatana K.;
RT "Enhancement of artemisinin content and biomass in Artemisia annua by
RT exogenous GA3 treatment.";
RL Plant Growth Regul. 63:45-54(2011).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=22195571; DOI=10.1016/j.plantsci.2011.10.019;
RA Olofsson L., Lundgren A., Brodelius P.E.;
RT "Trichome isolation with and without fixation using laser microdissection
RT and pressure catapulting followed by RNA amplification: expression of genes
RT of terpene metabolism in apical and sub-apical trichome cells of Artemisia
RT annua L.";
RL Plant Sci. 183:9-13(2012).
RN [12]
RP FUNCTION.
RX PubMed=24689216; DOI=10.1177/1934578X1400900320;
RA Karaket N., Wiyakrutta S., Lacaille-Dubois M.-A., Supaibulwatana K.;
RT "T-DNA insertion alters the terpenoid content composition and bioactivity
RT of transgenic Artemisia annua.";
RL Nat. Prod. Commun. 9:363-366(2014).
RN [13]
RP REVIEW ON ARTEMISININ ANTIMALARIAL PROPERTIES.
RX PubMed=27488942; DOI=10.1002/anie.201601967;
RA Tu Y.;
RT "Artemisinin-A Gift from Traditional Chinese Medicine to the World (Nobel
RT Lecture).";
RL Angew. Chem. Int. Ed. 55:10210-10226(2016).
RN [14]
RP PATHWAY, AND REVIEW.
RX PubMed=30468448; DOI=10.1039/c8np00077h;
RA Liu Y., Jing S.-X., Luo S.-H., Li S.-H.;
RT "Non-volatile natural products in plant glandular trichomes: chemistry,
RT biological activities and biosynthesis.";
RL Nat. Prod. Rep. 36:626-665(2019).
RN [15]
RP BIOTECHNOLOGY.
RX PubMed=32514287; DOI=10.1186/s13020-020-00336-8;
RA Uzun T., Toptas O.;
RT "Artesunate: could be an alternative drug to chloroquine in COVID-19
RT treatment?";
RL Chin. Med. J. 15:54-54(2020).
RN [16]
RP BIOTECHNOLOGY, AND REVIEW.
RX PubMed=32405226; DOI=10.1016/j.phrs.2020.104901;
RA Cheong D.H.J., Tan D.W.S., Wong F.W.S., Tran T.;
RT "Anti-malarial drug, artemisinin and its derivatives for the treatment of
RT respiratory diseases.";
RL Pharmacol. Res. 158:104901-104901(2020).
CC -!- FUNCTION: Involved in the biosynthesis of the antimalarial endoperoxide
CC artemisinin (Ref.7, Ref.9, PubMed:24689216, PubMed:10814821,
CC PubMed:27488942). Catalyzes the sequential condensation of isopentenyl
CC pyrophosphate with the allylic pyrophosphates, dimethylallyl
CC pyrophosphate, and then with the resultant geranylpyrophosphate to the
CC ultimate product farnesyl pyrophosphate (PubMed:8682304). Promotes
CC anti-malarial and antimicrobial (toward Gram-positive bacteria
CC B.subtilis and S.aureus) activities of plant crude extract probably by
CC triggering artemisinin levels (PubMed:24689216).
CC {ECO:0000269|PubMed:10814821, ECO:0000269|PubMed:24689216,
CC ECO:0000269|PubMed:8682304, ECO:0000269|Ref.7, ECO:0000269|Ref.9,
CC ECO:0000303|PubMed:27488942}.
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 Evidence={ECO:0000269|PubMed:8682304};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22409;
CC Evidence={ECO:0000269|PubMed:8682304};
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 Evidence={ECO:0000269|PubMed:8682304, ECO:0000269|Ref.7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19362;
CC Evidence={ECO:0000269|PubMed:8682304, ECO:0000269|Ref.7};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q12051};
CC Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051};
CC -!- PATHWAY: Isoprenoid biosynthesis; farnesyl diphosphate biosynthesis;
CC farnesyl diphosphate from geranyl diphosphate and isopentenyl
CC diphosphate: step 1/1. {ECO:0000269|PubMed:8682304, ECO:0000269|Ref.7}.
CC -!- PATHWAY: Sesquiterpene biosynthesis. {ECO:0000303|PubMed:30468448}.
CC -!- PATHWAY: Isoprenoid biosynthesis; geranyl diphosphate biosynthesis;
CC geranyl diphosphate from dimethylallyl diphosphate and isopentenyl
CC diphosphate: step 1/1. {ECO:0000269|PubMed:8682304}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O14230}. Nucleus
CC {ECO:0000250|UniProtKB:O14230}.
CC -!- TISSUE SPECIFICITY: Expressed both in apical and sub-apical cells of
CC glandular secretory trichomes. {ECO:0000269|PubMed:19664791,
CC ECO:0000269|PubMed:22195571}.
CC -!- INDUCTION: Strongly induced by gibberellic acid (GA(3)) leading to an
CC increased artemisinin yield. {ECO:0000269|Ref.10}.
CC -!- DISRUPTION PHENOTYPE: Reduced growth and lower artemisinin levels.
CC {ECO:0000269|Ref.9}.
CC -!- BIOTECHNOLOGY: Artemisinin and derivatives (e.g. artesunate), are
CC antimalarial drugs due to their endoperoxidase properties; they also
CC display multiple pharmacological actions against inflammation,viral
CC infections, and cell and tumor proliferation (PubMed:32514287,
CC PubMed:32405226). Artesunate may be a promising treatment for COVID-19
CC mediated by the severe acute respiratory syndrome coronavirus 2 (2019-
CC nCoV) (SARS-CoV-2) because of its anti-inflammatory activity, NF-kappaB
CC (nuclear factor kappa B)-coronavirus effect and chloroquine-like
CC endocytosis inhibition mechanism (PubMed:32514287, PubMed:32405226).
CC {ECO:0000303|PubMed:32405226, ECO:0000303|PubMed:32514287}.
CC -!- BIOTECHNOLOGY: Plants overexpressing FPS1 accumulate higher levels of
CC artemisinin. {ECO:0000269|PubMed:10814821, ECO:0000269|Ref.7,
CC ECO:0000269|Ref.9}.
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; U36376; AAC49452.1; -; mRNA.
DR EMBL; AF136602; AAD32648.1; -; mRNA.
DR EMBL; AF112881; AAD17204.1; -; mRNA.
DR EMBL; GQ420346; ADJ67472.1; -; mRNA.
DR EMBL; KJ609177; AIC83778.1; -; mRNA.
DR EMBL; PKPP01000340; PWA94011.1; -; Genomic_DNA.
DR PIR; JC4846; JC4846.
DR AlphaFoldDB; P49350; -.
DR SMR; P49350; -.
DR BioCyc; MetaCyc:MON-17882; -.
DR UniPathway; UPA00259; UER00368.
DR UniPathway; UPA00260; UER00369.
DR Proteomes; UP000245207; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004161; F:dimethylallyltranstransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004337; F:geranyltranstransferase activity; IEA:UniProtKB-EC.
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; IEA:UniProtKB-UniPathway.
DR GO; GO:0033384; P:geranyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009739; P:response to gibberellin; IEP:UniProtKB.
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 1: Evidence at protein level;
KW Cholesterol biosynthesis; Cholesterol metabolism; Cytoplasm;
KW Isoprene biosynthesis; Lipid biosynthesis; Lipid metabolism; Magnesium;
KW Metal-binding; Nucleus; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase.
FT CHAIN 1..343
FT /note="Farnesyl pyrophosphate synthase"
FT /id="PRO_0000123954"
FT BINDING 49
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 52
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 87
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 94
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 94
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 98
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 98
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 103
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 104
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 191
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 192
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 230
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 247
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 256
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT CONFLICT 4
FT /note="I -> T (in Ref. 1; AAC49452)"
FT /evidence="ECO:0000305"
FT CONFLICT 45
FT /note="V -> I (in Ref. 4; ADJ67472 and 5; AIC83778)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="P -> L (in Ref. 3; AAD17204, 4; ADJ67472, 5;
FT AIC83778 and 2; AAD32648)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="V -> E (in Ref. 4; ADJ67472 and 5; AIC83778)"
FT /evidence="ECO:0000305"
FT CONFLICT 154..156
FT /note="VEF -> GVI (in Ref. 2; AAD32648)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="T -> P (in Ref. 2; AAD32648)"
FT /evidence="ECO:0000305"
FT CONFLICT 221
FT /note="V -> M (in Ref. 3; AAD17204, 4; ADJ67472, 5;
FT AIC83778 and 2; AAD32648)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="A -> P (in Ref. 1; AAC49452)"
FT /evidence="ECO:0000305"
FT CONFLICT 275
FT /note="V -> T (in Ref. 1; AAC49452)"
FT /evidence="ECO:0000305"
FT CONFLICT 322
FT /note="H -> R (in Ref. 3; AAD17204, 4; ADJ67472, 5;
FT AIC83778 and 2; AAD32648)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 343 AA; 39404 MW; 0A49F4F28B4FE1A3 CRC64;
MSSIDLKSKF LKVYDTLKSE LINDPAFEFD DDSRQWIEKM LDYNVPGGKL NRGLSVVDSY
QLLKGGELSD DEIFLSSALG WCIEWLQAYF LVLDDIMDES HTRRGQPCWF RLPKVGMIAA
NDGILLRNHV PRILKKHFRG KPYYVDLVDL FNEVEFQTAS GQMIDLITTL VGEKDLSKYS
LSIHRRIVQY KTAYYSFYLP VACALLMFGE DLDKHVEVKN VLVEMGTYFQ VQDDYLDCFG
APEVIGKIGT DIEDFKCSWL VVKALELANE EQKKVLHENY GKKDPASVAK VKEVYHTLNL
QAVFEDYEAT SYKKLITSIE NHPSKAVQAV LKSFLGKIYK RQK
