C7BL2_LACSA
ID C7BL2_LACSA Reviewed; 490 AA.
AC F8S1I0;
DT 03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Costunolide synthase {ECO:0000303|PubMed:21515683};
DE Short=LsCOS {ECO:0000303|PubMed:21515683};
DE EC=1.14.14.150 {ECO:0000269|PubMed:21515683};
DE AltName: Full=Cytochrome P450 71BL2 {ECO:0000303|PubMed:21515683};
GN Name=CYP71BL2 {ECO:0000303|PubMed:21515683};
GN Synonyms=COS {ECO:0000303|PubMed:21515683};
OS Lactuca sativa (Garden lettuce).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Asterales; Asteraceae; Cichorioideae; Cichorieae;
OC Lactucinae; Lactuca.
OX NCBI_TaxID=4236;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND 3D-STRUCTURE
RP MODELING.
RC STRAIN=cv. Mariska;
RX PubMed=21515683; DOI=10.1074/jbc.m110.216804;
RA Ikezawa N., Gopfert J.C., Nguyen D.T., Kim S.U., O'Maille P.E., Spring O.,
RA Ro D.K.;
RT "Lettuce costunolide synthase (CYP71BL2) and its homolog (CYP71BL1) from
RT sunflower catalyze distinct regio- and stereoselective hydroxylations in
RT sesquiterpene lactone metabolism.";
RL J. Biol. Chem. 286:21601-21611(2011).
RN [2]
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).
CC -!- FUNCTION: Involved in the biosynthesis of germacrene-derived
CC sesquiterpene lactones (PubMed:30468448). Component of the parthenolide
CC biosynthetic pathway; parthenolide and conjugates are promising anti-
CC cancer drugs highly active against colon cancer cells
CC (PubMed:30468448). Hydroxylates germacrene A acid to 6-alpha-hydroxy-
CC germacrne A acid, a precursor of sesquiterpene lactones that
CC spontaneously undergoes a lactonization which yields costunolide
CC (PubMed:21515683). {ECO:0000269|PubMed:21515683,
CC ECO:0000303|PubMed:30468448}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=germacra-1(10),4,11(13)-trien-12-oate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (+)-costunolide + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:28230, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:3900, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:61301; EC=1.14.14.150;
CC Evidence={ECO:0000269|PubMed:21515683};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000303|PubMed:30468448}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type II
CC membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 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; HQ439599; AEI59780.1; -; mRNA.
DR AlphaFoldDB; F8S1I0; -.
DR SMR; F8S1I0; -.
DR EnsemblPlants; rna-gnl|WGS:NBSK|LSAT_7X33721_mrna; cds-PLY96629.1; gene-LSAT_7X33721.
DR Gramene; rna-gnl|WGS:NBSK|LSAT_7X33721_mrna; cds-PLY96629.1; gene-LSAT_7X33721.
DR KEGG; ag:AEI59780; -.
DR OrthoDB; 702827at2759; -.
DR BioCyc; MetaCyc:MON-18649; -.
DR BRENDA; 1.14.14.150; 2910.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0102934; F:costunolide synthase activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0051762; P:sesquiterpene biosynthetic process; IDA:UniProtKB.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..490
FT /note="Costunolide synthase"
FT /id="PRO_0000421931"
FT TRANSMEM 3..23
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT BINDING 432
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 255
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 490 AA; 55267 MW; 3C42A88E19EAD00B CRC64;
MEPLTIVSLA VASFLLFAFW ALSPKTSKNL PPGPPKLPII GNIHQLKSPT PHRVLRNLAK
KYGPIMHLQL GQVSTVVVST PRLAREIMKT NDISFADRPT TTTSQIFFYK AQDIGWAPYG
EYWRQMKKIC TLELLSAKKV RSFSSIREEE LRRISKVLES KAGTPVNFTE MTVEMVNNVI
CKATLGDSCK DQATLIEVLY DVLKTLSAFN LASYYPGLQF LNVILGKKAK WLKMQKQLDD
ILEDVLKEHR SKGRNKSDQE DLVDVLLRVK DTGGLDFTVT DEHVKAVVLD MLTAGTDTSS
ATLEWAMTEL MRNPHMMKRA QEEVRSVVKG DTITETDLQS LHYLKLIVKE TLRLHAPTPL
LVPRECRQAC NVDGYDIPAK TKILVNAWAC GTDPDSWKDA ESFIPERFEN CPINYMGADF
EFIPFGAGRR ICPGLTFGLS MVEYPLANFL YHFDWKLPNG LKPHELDITE ITGISTSLKH
QLKIVPILKS
