C7BL2_TANPA
ID C7BL2_TANPA Reviewed; 496 AA.
AC X2JE85;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 11-JUN-2014, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=Costunolide synthase {ECO:0000303|PubMed:24704560};
DE Short=TpCOS {ECO:0000303|PubMed:24704560};
DE EC=1.14.14.150 {ECO:0000269|PubMed:24704560};
DE AltName: Full=Cytochrome P450 71BL2 {ECO:0000305};
GN Name=CYP71BL2 {ECO:0000305}; Synonyms=COS {ECO:0000303|PubMed:24704560};
OS Tanacetum parthenium (Feverfew) (Matricaria parthenium).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Asterales; Asteraceae; Asteroideae; Anthemideae;
OC Anthemidinae; Tanacetum.
OX NCBI_TaxID=127999;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=24704560; DOI=10.1016/j.ymben.2014.03.005;
RA Liu Q., Manzano D., Tanic N., Pesic M., Bankovic J., Pateraki I.,
RA Ricard L., Ferrer A., de Vos R., van de Krol S., Bouwmeester H.;
RT "Elucidation and in planta reconstitution of the parthenolide biosynthetic
RT pathway.";
RL Metab. Eng. 23C:145-153(2014).
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 germacrene A acid, a precursor of sesquiterpene lactones that
CC spontaneously undergoes a lactonization which yields costunolide
CC (PubMed:24704560). {ECO:0000269|PubMed:24704560,
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:24704560};
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 -!- TISSUE SPECIFICITY: Expressed in floral glandular trichomes.
CC {ECO:0000269|PubMed:24704560}.
CC -!- DEVELOPMENTAL STAGE: During ovary development, accumulates until the
CC stage 3 and fades out progressively to disappear at stage 6.
CC {ECO:0000269|PubMed:24704560}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KC964545; AHN62856.1; -; mRNA.
DR AlphaFoldDB; X2JE85; -.
DR SMR; X2JE85; -.
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..496
FT /note="Costunolide synthase"
FT /id="PRO_5004949805"
FT TRANSMEM 4..24
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT BINDING 434
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 26
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 412
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 496 AA; 56267 MW; 8ABCF8C77B07BB62 CRC64;
MEPFTIFSLV VASLVFFACW ALVAPNTSKN LPPGPPKLPI IGNIHQLKSP TPHRVLKDLA
KKYGPIMHLQ LGQVSTVVVS TPRLAQEIMK TNDISFADRP TTTTSQIFFY KAQDIGWAPY
GEYWRQMKKI CTLELLSAKK VRSFSSIREE ELTRIRKILE FKAGTPINYT EMTIEMVNNV
ICKATLGDCC KDQALLIELL YDVLKTLSAF NLASYYPRLQ FLNVISGKKA KWLKMQKRLD
DIMEDILKEH RAKGRAKNSD QEDLVDVLLR IKDTGGLDIN VTDEHVKAVV LDMLTAGTDT
SSTTLEWAMT ELMRNPDMMK RAQEEVRSVV KGEHVTETDL QSLHYLKLIV KETMRLHAPT
PLLVPRECRQ DCNVDGYDIP AKTKVLVNAW ACGVDPGSWE NPDSFIPERF ENSSINFMGA
DFQYIPFGAG RRICPGLTFG LSMVEYPLAH FLYHFDWKLP YGMKPHELDI TEITTISTSL
KHHLKIVPFP KSSLAK
