C7A27_EUPLT
ID C7A27_EUPLT Reviewed; 500 AA.
AC A0A161GJD5;
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 726A27 {ECO:0000303|PubMed:27506796};
DE Short=ElCYP726A27 {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=4-hydroxycasbene synthase {ECO:0000305|PubMed:27506796};
DE EC=1.14.14.- {ECO:0000269|PubMed:27506796};
GN Name=CYP726A27 {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 8-hydroxycasbene to produce 4-
CC hydroxycasbene and 4,8-dihydroxycasbene, respectively
CC (PubMed:27506796). {ECO:0000269|PubMed:27506796}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(-)-casbene + O2 + reduced [NADPH--hemoprotein reductase] = 4-
CC hydroxycasbene + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:65588, 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:157595; Evidence={ECO:0000269|PubMed:27506796};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65589;
CC Evidence={ECO:0000269|PubMed:27506796};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8-hydroxycasbene + O2 + reduced [NADPH--hemoprotein reductase]
CC = 4,8-dihydroxycasbene + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:65592, 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:157600,
CC ChEBI:CHEBI:157601; Evidence={ECO:0000269|PubMed:27506796};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65593;
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; KR350669; AMY98419.1; -; mRNA.
DR SMR; A0A161GJD5; -.
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..500
FT /note="Cytochrome P450 726A27"
FT /id="PRO_0000453168"
FT TRANSMEM 7..27
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT BINDING 440
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 500 AA; 56562 MW; 5AEB929D1C34ED36 CRC64;
MDLQLQIPSY PIIFSFFIFI FMLIKIWKKQ TQTSIFPPGP FKFPIVGNIP QLATGGTLPH
HRLRDLAKIY GPIMTIQLGQ VKSVVISSPE TAKEVLKTQD IQFADRPLLL AGEMVLYNRK
DILYGTYGDQ WRQMRKICTL ELLSAKRIQS FKSVREKEVE SFIKTLRSKS GIPVNLTNAV
FELTNTIMMI TTIGQKCKNQ EAVMSVIDRV SEAAAGFSVA DVFPSLKFLH YLSGEKTKLQ
KLHKETDQIL EEIISEHKAN AKVGAQADNL LDVLLDLQKN GNLQVPLTND NIKAATLEMF
GAGSDTSSKT TDWAMAQMMR KPTTMKKAQE EVRRVFGENG KVEESRIQEL KYLKLVVKET
LRLHPAVALI PRECREKTKI DGFDIYPKTK ILVNPWAIGR DPKVWNEPES FNPERFQDSP
IDYKGTNFEL IPFGAGKRIC PGMTLGITNL ELFLANLLYH FDWKFPDGIT SENLDMTEAI
GGAIKRKLDL ELISIPYTSS
