C71A1_TANPA
ID C71A1_TANPA Reviewed; 506 AA.
AC X2EVV9;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 11-JUN-2014, sequence version 1.
DT 03-AUG-2022, entry version 21.
DE RecName: Full=Parthenolide synthase {ECO:0000303|PubMed:24704560};
DE Short=Tp2116 {ECO:0000303|PubMed:24704560};
DE Short=TpPTS {ECO:0000303|PubMed:24704560};
DE EC=1.14.14.- {ECO:0000269|PubMed:24704560};
DE AltName: Full=Cytochrome P450 71CA1 {ECO:0000305};
GN Name=CYP71CA1 {ECO:0000303|PubMed:24704560};
GN Synonyms=PTS {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, AND DEVELOPMENTAL
RP 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). Catalyzes the conversion of costunolide to
CC parthenolide (PubMed:24704560). {ECO:0000269|PubMed:24704560,
CC ECO:0000303|PubMed:30468448}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-costunolide + O2 + reduced [NADPH--hemoprotein reductase]
CC = H(+) + H2O + oxidized [NADPH--hemoprotein reductase] +
CC parthenolide; Xref=Rhea:RHEA:61320, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:3900, ChEBI:CHEBI:7939, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:24704560};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61321;
CC Evidence={ECO:0000269|PubMed:24704560};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000303|PubMed:30468448}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
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; KC954155; AHM24033.1; -; mRNA.
DR AlphaFoldDB; X2EVV9; -.
DR SMR; X2EVV9; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0102626; F:parthenolide synthase activity; IDA:UniProtKB.
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; Transmembrane; Transmembrane helix.
FT CHAIN 1..506
FT /note="Parthenolide synthase"
FT /id="PRO_0000448398"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 301..321
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 448
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 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 121
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 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 506 AA; 57788 MW; A8FE9B60F4688FC8 CRC64;
MDTSTSFPSL FLPTLCTILI SYIIIKYVLI WNRSSMAAFN LPPSPPKLPI IGNIHHVFSK
NVNQTLWKLS KKYGPVMLID TGAKSFLVVS SSQMAMEVLK THQEILSTRP SNEGTKRLSY
NFSDITFSPH GDHWRDMRKV FVNEFLGPKR AGWFNQVLRM EIKDVINNLS SNPLNTSINL
NEMLLSLVYR VVCKFAFGKS YREEPFNGVT LKEMLDESMV VLAGSSADMF PTFGWILDKL
YGWNDRLEKC FGNLDGFFEM IINEHLQSAS ETSEDEKDFV HSLVELSLKD PQFTKDYIKA
LLLNVLLGAI DTTFTTIVWA MSEIVKNTQV MQKLQTEIRS CIGRKEEVDA TDLTNMAYLK
MVIKETLRLH PPAPLLFPRE CPSHCKIGGY DVFPGTCVVM NGWGIARDPN VWKEIPNEFY
PERFENFNID FLGNHCEMIP FGAGRRSCPG MKSATSTIEF TLVNLLYWFD WEVPSGMNNQ
DLDMEEDGFL VIQKKSPLFL IPIKHI
