C7D45_EUPLT
ID C7D45_EUPLT Reviewed; 513 AA.
AC A0A165U5Z9;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 06-JUL-2016, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=Cytochrome P450 71D445 {ECO:0000303|PubMed:27506796};
DE Short=ElCYP71D445 {ECO:0000303|PubMed:27506796};
DE AltName: Full=4,5,8-trihydroxycasbene synthase {ECO:0000305|PubMed:27506796};
DE EC=1.14.14.- {ECO:0000269|PubMed:27506796};
DE AltName: Full=4,8-dihydroxycasbene synthase {ECO:0000305|PubMed:27506796};
DE EC=1.14.14.- {ECO:0000269|PubMed:27506796};
DE AltName: Full=8-hydroxycasbene synthase {ECO:0000305|PubMed:27506796};
DE EC=1.14.14.- {ECO:0000269|PubMed:27506796};
GN Name=CYP71D445 {ECO:0000303|PubMed:27506796};
OS Euphorbia lathyris (Caper spurge).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; fabids; Malpighiales; Euphorbiaceae; Euphorbioideae; Euphorbieae;
OC Euphorbia; Euphorbia subgen. Esula; Euphorbia sect. Lathyris.
OX NCBI_TaxID=212925;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Seed;
RX PubMed=27506796; DOI=10.1073/pnas.1607504113;
RA Luo D., Callari R., Hamberger B., Wubshet S.G., Nielsen M.T.,
RA Andersen-Ranberg J., Hallstroem B.M., Cozzi F., Heider H.,
RA Lindberg Moeller B., Staerk D., Hamberger B.;
RT "Oxidation and cyclization of casbene in the biosynthesis of Euphorbia
RT factors from mature seeds of Euphorbia lathyris L.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:E5082-E5089(2016).
CC -!- FUNCTION: Involved in the biosynthesis of macrocyclic lathyrane type
CC diterpenoids (also called Euphorbia factors) natural products,
CC including the cyclization route from casbene to jolkinol C, a precursor
CC for ingenol mebutate that is used to treat actinic keratosis, a
CC precancerous skin condition (PubMed:27506796). Catalyzes the
CC hydroxylation of (-)-casbene and 4-hydroxycasbene to produce 8-
CC hydroxycasbene and 4,8-dihydroxycasbene, respectively
CC (PubMed:27506796). Mediates also the formation of 4-hydroxy-8-
CC ketocasbene from 4,8-dihydroxycasbene (PubMed:27506796). Together with
CC ADH1, triggers the biosynthesis of 8-ketocasbene from 8-hydroxycasbene
CC (PubMed:27506796). {ECO:0000269|PubMed:27506796}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(-)-casbene + O2 + reduced [NADPH--hemoprotein reductase] = 8-
CC hydroxycasbene + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:65584, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:157595,
CC ChEBI:CHEBI:157600; Evidence={ECO:0000269|PubMed:27506796};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65585;
CC Evidence={ECO:0000269|PubMed:27506796};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxycasbene + O2 + reduced [NADPH--hemoprotein reductase]
CC = 4,8-dihydroxycasbene + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:65596, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:156578,
CC ChEBI:CHEBI:157601; Evidence={ECO:0000269|PubMed:27506796};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65597;
CC Evidence={ECO:0000269|PubMed:27506796};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,8-dihydroxycasbene + O2 + reduced [NADPH--hemoprotein
CC reductase] = 4,5,8-trihydroxycasbene + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:67032, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:157601, ChEBI:CHEBI:157602;
CC Evidence={ECO:0000269|PubMed:27506796};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67033;
CC Evidence={ECO:0000269|PubMed:27506796};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q96242};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:27506796}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type II
CC membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in mature seeds.
CC {ECO:0000269|PubMed:27506796}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KR350668; AMY98418.1; -; mRNA.
DR SMR; A0A165U5Z9; -.
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:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
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 Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..513
FT /note="Cytochrome P450 71D445"
FT /id="PRO_0000453167"
FT TRANSMEM 12..28
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT BINDING 450
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:Q96242"
SQ SEQUENCE 513 AA; 58226 MW; A65613A750561AD3 CRC64;
MELEFRSPSS PSEWAITSTI TLLFLILLRK ILKPKTPTPN LPPGPKKLPL IGNIHQLIGG
IPHQKMRDLS QIHGPIMHLK LGELENVIIS SKEAAEKILK THDVLFAQRP QMIVAKSVTY
DFHDITFSPY GDYWRQLRKI TMIELLAAKR VLSFRAIREE ETTKLVELIR GFQSGESINF
TRMIDSTTYG ITSRAACGKI WEGENLFISS LEKIMFEVGS GISFADAYPS VKLLKVFSGI
RIRVDRLQKN IDKIFESIIE EHREERKGRK KGEDDLDLVD VLLNLQESGT LEIPLSDVTI
KAVIMDMFVA GVDTSAATTE WLMSELIKNP EVMKKAQAEI REKFKGKASI DEADLQDLHY
LKLVIKETFR LHPSVPLLVP RECRESCVIE GYDIPVKTKI MVNAWAMGRD TKYWGEDAEK
FKPERFIDSP IDFKGHNFEY LPFGSGRRSC PGMAFGVANV EIAVAKLLYH FDWRLGDGMV
PENLDMTEKI GGTTRRLSEL YIIPTPYVPQ NSA
