ID   MSH_PAPSO               Reviewed;         526 AA.
AC   L7X3S1;
DT   03-SEP-2014, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2013, sequence version 1.
DT   03-AUG-2022, entry version 28.
DE   RecName: Full=Methyltetrahydroprotoberberine 14-monooxygenase;
DE            EC=1.14.14.97 {ECO:0000269|PubMed:23313486};
DE   AltName: Full=(S)-cis-N-methylstylopine 14-hydroxylase;
DE   AltName: Full=(S)-cis-N-methyltetrahydroprotoberberine-14-hydroxylase;
DE   AltName: Full=Methyltetrahydroprotoberberine 14-hydroxylase;
DE   AltName: Full=N-methylstylopine hydroxylase;
DE            Short=MSH;
GN   Name=CYP82N4;
OS   Papaver somniferum (Opium poppy).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; Ranunculales; Papaveraceae; Papaveroideae;
OC   Papaver.
OX   NCBI_TaxID=3469;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PATHWAY, AND CATALYTIC ACTIVITY.
RX   PubMed=23313486; DOI=10.1016/j.bbrc.2012.12.129;
RA   Beaudoin G.A., Facchini P.J.;
RT   "Isolation and characterization of a cDNA encoding (S)-cis-N-
RT   methylstylopine 14-hydroxylase from opium poppy, a key enzyme in
RT   sanguinarine biosynthesis.";
RL   Biochem. Biophys. Res. Commun. 431:597-603(2013).
CC   -!- FUNCTION: Catalyzes the conversion of N-methylated protoberberine
CC       alkaloids N-methylstylopine and N-methylcanadine into protopine and
CC       allocryptopine, respectively, in the biosynthesis of isoquinoline
CC       alkaloid sanguinarine. {ECO:0000269|PubMed:23313486}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-N-methylcanadine + O2 + reduced [NADPH--hemoprotein
CC         reductase] = allocryptopine + 2 H(+) + H2O + oxidized [NADPH--
CC         hemoprotein reductase]; Xref=Rhea:RHEA:23684, Rhea:RHEA-COMP:11964,
CC         Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:16512, ChEBI:CHEBI:17390,
CC         ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.97;
CC         Evidence={ECO:0000269|PubMed:23313486};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC   -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:23313486}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC       protein {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; KC154003; AGC92398.1; -; mRNA.
DR   AlphaFoldDB; L7X3S1; -.
DR   SMR; L7X3S1; -.
DR   KEGG; ag:AGC92398; -.
DR   BioCyc; MetaCyc:MON-18686; -.
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:0047084; F:methyltetrahydroprotoberberine 14-monooxygenase activity; IDA:UniProtKB.
DR   GO; GO:0033075; P:isoquinoline alkaloid 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   Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..526
FT                   /note="Methyltetrahydroprotoberberine 14-monooxygenase"
FT                   /id="PRO_0000430260"
FT   TRANSMEM        14..34
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         468
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"
SQ   SEQUENCE   526 AA;  59346 MW;  37F4A26D4AA15864 CRC64;
     MRTESIKTNR PMDLLLQYLQ PISVALVVIA LVWNYGRRNP TKKLAPEASG GRPIMGHLHL
     FNDGELTHRK LGAMADTYGP VFNIRFGSHK TLVVSDWEIV KECFTTNDKL FSNRPGTLGI
     KLMFYDADSV GYAPYGAYWR DLRKISTLKL LSNHRIDTIK HLRSSEVESC FESLYSQWGN
     GEKSGEFAPV RMDSWLGDLT FNVVARIVAG KKNFSANGDV GAQRYKAAMD EAMRLMRFFA
     FSDVIPSLSW LDNLRGLVRE MKKCASEIDS IMATWVEEHR VKRNSGGNSQ LEHDFIDVCL
     DIMEHSSLPG DDPDLVVKST CLDMILGGSD TTTVTLTWAM SLLLNHPQVL QKAKEELETQ
     VGKNRQVDDS DIPNLPFIQA IIKETMRLYP AGPLIERRTM EDCEVAGYQV PAGTRLLVNV
     WKMQRDGNVY KGDPLEFRPD RFLTSNADVD LKGQHYELIP FGAGRRICPG VSFAVQLMHL
     VLARLLHEFE ITTVEPETKV DMAESGGLLC YKIMPLEVLI KPRLEI