ID   ECS1_ARTAN              Reviewed;         547 AA.
AC   Q9LLR9; Q9ST45;
DT   28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   03-AUG-2022, entry version 78.
DE   RecName: Full=Epi-cedrol synthase;
DE            EC=4.2.3.39;
DE   AltName: Full=8-epicedrol synthase;
GN   Name=ECS1;
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], AND FUNCTION.
RX   PubMed=10486139; DOI=10.1006/abbi.1999.1357;
RA   Hua L., Matsuda S.P.;
RT   "The molecular cloning of 8-epicedrol synthase from Artemisia annua.";
RL   Arch. Biochem. Biophys. 369:208-212(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND BIOPHYSICOCHEMICAL PROPERTIES.
RC   TISSUE=Leaf;
RX   PubMed=10486140; DOI=10.1006/abbi.1999.1358;
RA   Mercke P., Xue Z.T., Brodelius P.E.;
RT   "Cloning, expression, and characterization of epi-cedrol synthase, a
RT   sesquiterpene cyclase from Artemisia annua L.";
RL   Arch. Biochem. Biophys. 369:213-222(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=10996256; DOI=10.1016/s0168-9452(00)00322-8;
RA   Van Geldre E., De Pauw I., Inze D., Van Montagu M., Van den Eeckhout E.;
RT   "Cloning and molecular analysis of two new sesquiterpene cyclases from
RT   Artemisia annua L.";
RL   Plant Sci. 158:163-171(2000).
CC   -!- FUNCTION: Sesquiterpene cyclase catalyzing the production of 8-epi-
CC       cedrol. Able to convert geranyl diphosphate to monoterpens. Can use
CC       farnesyl diphosphate or geranyl diphosphate as substrates, but not
CC       geranylgeranyl diphosphate. Probably not involved in artemisinin
CC       biosynthesis. {ECO:0000269|PubMed:10486139}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2E,6E)-farnesyl diphosphate + H2O = diphosphate + epi-cedrol;
CC         Xref=Rhea:RHEA:26115, ChEBI:CHEBI:15377, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:52226, ChEBI:CHEBI:175763; EC=4.2.3.39;
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC       Note=Binds 3 Mg(2+) or Mn(2+) ions per subunit. {ECO:0000250};
CC   -!- ACTIVITY REGULATION: Inhibited by high concentration of manganese.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.4 uM for farnesyl diphosphate (at pH 7.0)
CC         {ECO:0000269|PubMed:10486140};
CC         KM=1.3 uM for farnesyl diphosphate (at pH 9.0)
CC         {ECO:0000269|PubMed:10486140};
CC         KM=80 uM for magnesium (at pH 7.0) {ECO:0000269|PubMed:10486140};
CC         KM=80 uM for magnesium (at pH 9.0) {ECO:0000269|PubMed:10486140};
CC       pH dependence:
CC         Optimum pH is 8.5-9.0. {ECO:0000269|PubMed:10486140};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC   -!- TISSUE SPECIFICITY: Constitutively expressed in leaves and flowers.
CC       {ECO:0000269|PubMed:10996256}.
CC   -!- DOMAIN: The Asp-Asp-Xaa-Xaa-Asp/Glu (DDXXD/E) motif is important for
CC       the catalytic activity, presumably through binding to Mg(2+).
CC   -!- SIMILARITY: Belongs to the terpene 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; AF157059; AAF80333.1; -; mRNA.
DR   EMBL; AJ001539; CAC08805.1; -; mRNA.
DR   EMBL; AJ249561; CAB56499.1; -; mRNA.
DR   AlphaFoldDB; Q9LLR9; -.
DR   SMR; Q9LLR9; -.
DR   KEGG; ag:AAF80333; -.
DR   BioCyc; MetaCyc:MON-16025; -.
DR   BRENDA; 4.2.3.39; 7150.
DR   UniPathway; UPA00213; -.
DR   GO; GO:0052682; F:epi-cedrol synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR   GO; GO:0010333; F:terpene synthase activity; IEA:InterPro.
DR   GO; GO:0016102; P:diterpenoid biosynthetic process; IEA:InterPro.
DR   CDD; cd00684; Terpene_cyclase_plant_C1; 1.
DR   Gene3D; 1.10.600.10; -; 1.
DR   Gene3D; 1.50.10.130; -; 1.
DR   InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR   InterPro; IPR034741; Terpene_cyclase-like_1_C.
DR   InterPro; IPR044814; Terpene_cyclase_plant_C1.
DR   InterPro; IPR001906; Terpene_synth_N.
DR   InterPro; IPR036965; Terpene_synth_N_sf.
DR   InterPro; IPR005630; Terpene_synthase_metal-bd.
DR   InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR   Pfam; PF01397; Terpene_synth; 1.
DR   Pfam; PF03936; Terpene_synth_C; 1.
DR   SFLD; SFLDG01019; Terpene_Cyclase_Like_1_C_Termi; 1.
DR   SUPFAM; SSF48239; SSF48239; 1.
DR   SUPFAM; SSF48576; SSF48576; 1.
PE   1: Evidence at protein level;
KW   Lyase; Magnesium; Manganese; Metal-binding.
FT   CHAIN           1..547
FT                   /note="Epi-cedrol synthase"
FT                   /id="PRO_0000380670"
FT   MOTIF           299..303
FT                   /note="DDXXD motif"
FT   BINDING         299
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         299
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         303
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         303
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         443
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         447
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         451
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        185
FT                   /note="V -> I (in Ref. 3; CAB56499)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   547 AA;  63564 MW;  E84EE9FCEED70BE2 CRC64;
     MSLIVEDVIR PNANFPSEIW GDQFLAYDQD EQEGVEQVIK DLKEEVKSEL LTALNSPTQH
     TELLKFIDAI ERLGIAYYFE EEINQVFQHM YTAYGDKWTG GNTSLWFRLM RQHGFFVSSD
     IFSTYKDKEG RFKESLEKDV HGLLELYEAA YMFVPGEGIL DDALVFTRTC LDEIAKNPSL
     SNSAVSSQIR EALTQPLHKR LPRLEALRYI PFYQQQASHS ETLLKLAKLG FNQLQSLHKK
     ELSIISKWWK SFDVANNLPY ARNRPVECYF WALAVYFEPQ YSESRVFLSR FFSIQTFLDD
     TYDAYGTYEE LEQFTEAIQR WSITCLDGLP ESMKLIFQML VKIFEEIEEI LSKDGKQHHV
     NYIKETLKEA VQSYMTEARW AKEEYIPTIE EHTKVSYISI GYKLALVAGF ACMGDVIADD
     SFEWVFTNPP LVNACCLLCR TMDDLGSHKG EQDRKHVAST IECYMKQFDA SEQQAYESLN
     KKVEDAWKEI NREFMITCKD VNIHVAMRVL NFSRSVDVLY KNKDHFTHVG VEVINHIKSL
     FVDAIIT