KSL3_ISORU
ID KSL3_ISORU Reviewed; 782 AA.
AC A0A1X9ISH5; A0A1W6QDI4;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 2.
DT 03-AUG-2022, entry version 26.
DE RecName: Full=Nezukol synthase KSL3 {ECO:0000303|PubMed:28445526};
DE EC=4.2.3.183 {ECO:0000269|PubMed:28445526};
DE AltName: Full=Kaurene synthase 3 {ECO:0000303|PubMed:28381502};
DE Short=IrKSL3 {ECO:0000303|PubMed:28381502};
DE AltName: Full=Miltiradiene synthase KSL3 {ECO:0000305};
DE EC=4.2.3.131 {ECO:0000269|PubMed:28381502};
DE AltName: Full=Terpene synthase 2 {ECO:0000303|PubMed:28445526};
DE Short=IrTPS2 {ECO:0000303|PubMed:28445526};
GN Name=KSL3 {ECO:0000303|PubMed:28381502};
GN Synonyms=TPS2 {ECO:0000303|PubMed:28445526};
OS Isodon rubescens (Rabdosia rubescens).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; lamiids; Lamiales; Lamiaceae; Nepetoideae; Ocimeae; Isodoninae;
OC Isodon.
OX NCBI_TaxID=587669;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PATHWAY, CATALYTIC ACTIVITY, AND
RP TISSUE SPECIFICITY.
RX PubMed=28381502; DOI=10.1104/pp.17.00202;
RA Jin B., Cui G., Guo J., Tang J., Duan L., Lin H., Shen Y., Chen T.,
RA Zhang H., Huang L.;
RT "Functional diversification of kaurene synthase-like genes in Isodon
RT rubescens.";
RL Plant Physiol. 174:943-955(2017).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PATHWAY, CATALYTIC ACTIVITY, AND
RP TISSUE SPECIFICITY.
RX PubMed=28445526; DOI=10.1371/journal.pone.0176507;
RA Pelot K.A., Hagelthorn L.M., Addison J.B., Zerbe P.;
RT "Biosynthesis of the oxygenated diterpene nezukol in the medicinal plant
RT Isodon rubescens is catalyzed by a pair of diterpene synthases.";
RL PLoS ONE 12:e0176507-e0176507(2017).
CC -!- FUNCTION: Involved in the biosynthesis of ent-kaurene diterpenoids
CC natural products such as oridonin, miltiradiene, eriocalyxin B and
CC nezukol, known to exhibit antitumor, anti-inflammatory and
CC antibacterial activities (PubMed:28381502, PubMed:28445526). Catalyzes
CC the conversion of (+)-copalyl diphosphate ((+)-CPP) to nezukol and
CC miltiradiene (PubMed:28381502, PubMed:28445526). The reaction mechanism
CC proceeds via the ionization of the diphosphate group of (+)-CPP,
CC followed by formation of an intermediary pimar-15-en-8-yl(+)
CC carbocation and neutralization of the carbocation by water capture at
CC C-8 to yield nezukol (PubMed:28445526). Can interact with ent-copalyl
CC diphosphate (ent-CPP) but seems unable to use it as substrate
CC (PubMed:28445526). {ECO:0000269|PubMed:28381502,
CC ECO:0000269|PubMed:28445526}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-copalyl diphosphate = diphosphate + miltiradiene;
CC Xref=Rhea:RHEA:33983, ChEBI:CHEBI:33019, ChEBI:CHEBI:58635,
CC ChEBI:CHEBI:65037; EC=4.2.3.131;
CC Evidence={ECO:0000269|PubMed:28381502};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33984;
CC Evidence={ECO:0000269|PubMed:28381502};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-copalyl diphosphate + H2O = diphosphate + nezukol;
CC Xref=Rhea:RHEA:54376, ChEBI:CHEBI:15377, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:58635, ChEBI:CHEBI:138166; EC=4.2.3.183;
CC Evidence={ECO:0000269|PubMed:28445526};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54377;
CC Evidence={ECO:0000269|PubMed:28445526};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q40577};
CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q40577};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:28381502}.
CC -!- TISSUE SPECIFICITY: Highly expressed in leaves, and, at low levels, in
CC stems, but barely in roots and flowers. {ECO:0000269|PubMed:28381502,
CC ECO:0000269|PubMed:28445526}.
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 {ECO:0000305}.
CC -!- MISCELLANEOUS: Abietane diterpenoids (e.g. miltiradiene, abietatriene
CC and ferruginol) accumulate specifically in the periderm of roots
CC (PubMed:28381502). The ent-kaurene diterpenoid oridonin, main
CC constituent of Isodon rubescens, accumulates in leaves
CC (PubMed:28381502). {ECO:0000269|PubMed:28381502}.
CC -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
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DR EMBL; KU180506; APJ36378.2; -; mRNA.
DR EMBL; KX831650; ARO38140.1; -; mRNA.
DR AlphaFoldDB; A0A1X9ISH5; -.
DR SMR; A0A1X9ISH5; -.
DR KEGG; ag:ARO38140; -.
DR BRENDA; 4.2.3.183; 15342.
DR UniPathway; UPA00213; -.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0062205; F:miltiradiene synthase activity; IDA:UniProtKB.
DR GO; GO:0010333; F:terpene synthase activity; IEA:InterPro.
DR GO; GO:1901946; P:miltiradiene biosynthetic process; IDA:UniProtKB.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IDA:UniProtKB.
DR Gene3D; 1.10.600.10; -; 1.
DR Gene3D; 1.50.10.130; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
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 SUPFAM; SSF48239; SSF48239; 2.
DR SUPFAM; SSF48576; SSF48576; 1.
PE 1: Evidence at protein level;
KW Lyase; Magnesium; Metal-binding.
FT CHAIN 1..782
FT /note="Nezukol synthase KSL3"
FT /id="PRO_0000452384"
FT MOTIF 529..533
FT /note="DDXXD motif"
FT /evidence="ECO:0000305"
FT BINDING 529
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 529
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 533
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 533
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 677
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 685
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT CONFLICT 60
FT /note="E -> D (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="S -> T (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="A -> S (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="A -> P (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 197
FT /note="I -> IR (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="Q -> E (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="M -> K (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="A -> S (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 522..523
FT /note="IL -> AI (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 551..556
FT /note="Missing (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 603
FT /note="E -> V (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 638
FT /note="E -> K (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 670
FT /note="N -> S (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 698
FT /note="V -> A (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 722
FT /note="E -> K (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
FT CONFLICT 775
FT /note="G -> D (in Ref. 2; ARO38140)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 782 AA; 89155 MW; B32EFBB14349A145 CRC64;
MSTLKLIPFS TSIDKQFSGR TSILGGKCCL QIDGPKTTKK QSKILVEKIR ERISNGKVVE
ISASAYDTAW VAMVPSREMS GRPSFPECLD WIVENQNPDG SWGLNPFLVK DSLSCTLACL
LALRKWGLPN HLLHKGIEFI ESNISRAATD DENQVAPIGF NIIFPAMISY AKELDLTLTL
PPSSLNALLR ARDSEMIRRE GKWEYVGEGL GDSCNWNQII QKHQSRNGSL FNSPATTAAA
AIHCRDHKCF DYLISVVNKC NGWAPTVYPM DIYARLCMID TLQRLGIDCH FRVELDAIFD
EIYRNWQERE EEIFSDVTCQ ALAFRLLRVK GYDVSSDGLE EFVEQEGFFN SVSMQHSNVG
TVLELYRASQ TRINEEENTL QKIHAWTKPF LTQQLLNKTI RHKPLQMQVE YDLKNFYGTV
DRFQHRRTID LYDAQASQIL KTAYRCSAIH NEDFIRFSVQ NFKICRAEYQ KELDEINKWY
AYFGMDLLSK GRNACEQAYV VTAGLIADVE LSMARISFAQ VILLITVFDD VFDRYGTREE
ALAVIHLIKE ILTHYRWKAA PKECSQLVKT TFTALYDTVN ETAAKAHALQ GFCFKQQIIS
LWEELLECAV REKESLSGKN VSTLDEYLSF APVTIGCELC VLTAVHFLGI QVSEEMLTSA
EMLTLCWHGN VVCRLLNDLK TYSREREEKT VNSVSVQVGV SEEEAVAKVK EVLEYHRRKV
VEMVYQSQGS NVPRECKELV WKTCKVAHCF YGYDGDEFSS PRDIVDDIKA MMFLGLPHLS
TH
