ID   CYPH3_ISORU             Reviewed;         492 AA.
AC   A0A1Z3GBS4;
DT   07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT   27-SEP-2017, sequence version 1.
DT   03-AUG-2022, entry version 13.
DE   RecName: Full=Ferruginol synthase {ECO:0000303|PubMed:28381502};
DE            EC=1.14.14.175 {ECO:0000269|PubMed:28381502};
DE   AltName: Full=Cytochrome P450 76AH30 {ECO:0000303|PubMed:28381502};
GN   Name=CYP76AH30 {ECO:0000303|PubMed:28381502};
OS   Isodon rubescens (Rabdosia rubescens).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   asterids; lamiids; Lamiales; Lamiaceae; Nepetoideae; Ocimeae; Isodoninae;
OC   Isodon.
OX   NCBI_TaxID=587669;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PATHWAY, AND CATALYTIC ACTIVITY.
RX   PubMed=28381502; DOI=10.1104/pp.17.00202;
RA   Jin B., Cui G., Guo J., Tang J., Duan L., Lin H., Shen Y., Chen T.,
RA   Zhang H., Huang L.;
RT   "Functional diversification of kaurene synthase-like genes in Isodon
RT   rubescens.";
RL   Plant Physiol. 174:943-955(2017).
CC   -!- FUNCTION: Cytochrome P450 enzyme (CYP) which catalyzes a unique two-
CC       electron oxidation cascade on abieta-8,11,13-triene to produce
CC       ferruginol, an intermediate in tanshinone biosynthesis.
CC       {ECO:0000269|PubMed:28381502}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=abieta-8,11,13-triene + O2 + reduced [NADPH--hemoprotein
CC         reductase] = ferruginol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:48080, 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:78274,
CC         ChEBI:CHEBI:86062; EC=1.14.14.175;
CC         Evidence={ECO:0000269|PubMed:28381502};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48081;
CC         Evidence={ECO:0000269|PubMed:28381502};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:Q00441};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:28381502}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC       Single-pass membrane protein {ECO:0000255}.
CC   -!- BIOTECHNOLOGY: Ferruginol is a widespread diterpenoid metabolite that
CC       serves as a bioactive natural product in its own right, and has been
CC       shown to exhibit a range of activities similar to that of the
CC       tanshinones such as anti-tumor and antibacterial properties. It
CC       therefore contributes to the medicinal effect of Isodon rubescens.
CC       {ECO:0000303|PubMed:28381502}.
CC   -!- MISCELLANEOUS: Abietane diterpenoids (e.g. miltiradiene, abietatriene
CC       and ferruginol) accumulate specifically in the periderm of roots
CC       (PubMed:28381502). The ent-kaurene diterpenoid oridonin, main
CC       constituent of Isodon rubescens, accumulates in leaves
CC       (PubMed:28381502). {ECO:0000269|PubMed:28381502}.
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; KX580636; ASC55319.1; -; mRNA.
DR   AlphaFoldDB; A0A1Z3GBS4; -.
DR   SMR; A0A1Z3GBS4; -.
DR   UniPathway; UPA00213; -.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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:1901946; P:miltiradiene biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IDA:UniProtKB.
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   Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW   NADP; Oxidoreductase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..492
FT                   /note="Ferruginol synthase"
FT                   /id="PRO_5013119921"
FT   TRANSMEM        1..21
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        22..492
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   BINDING         436
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:S4UX02"
SQ   SEQUENCE   492 AA;  55567 MW;  D54BAFA11F84D0BB CRC64;
     METIALLAAL FFIALTCFLT SGRRRNLPPG PYPLPIIGNM LQLGSNPHQS FAQLSKKYGP
     LMSIHLGSLY TVIVSSPEMA KEILHKHGQA FSGRTIAQAV HACDHDKISM GFLPVTSVWR
     DLRKICKEQM FSHQSLEASE GLRHQKLQQL LDYAQKCCET GRAVDIREAS FITTLNLMSA
     TMFSTQATEF ESEATKEFKE IIEGVATIVG VPNFADYFPI LKPFDLQGIK RQADGYFGRL
     LKKIEGYLNE RVESRRLNPD APRKNDFLET VVDIIEADEY KLTTDHLTHL MLDLFVGGSE
     TNTTSLEWIM SELVINPDKM AKVKDEIKSV VGDKKIVDES EMPRLPYLQA AIKEVLRIHP
     PGPLLLPRRA EIDQEVNGYL IPKGTQILFN AWAIGRDPSI WKNPESFEPE RFLDQTVDFK
     GQDFELIPFG SGRRICPGMP LANRILHMTT ATLVHNFDWK LEEETANADH QDELFGLAVR
     RAVPLKIIPL RP