ID   C71DI_MENSP             Reviewed;         496 AA.
AC   Q9XHE8;
DT   24-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   27-MAR-2024, entry version 94.
DE   RecName: Full=Cytochrome P450 71D18;
DE            EC=1.14.14.51 {ECO:0000269|PubMed:10415126, ECO:0000269|PubMed:11368174};
DE   AltName: Full=(-)-(4S)-Limonene-6-hydroxylase;
GN   Name=CYP71D18;
OS   Mentha spicata (Spearmint).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   asterids; lamiids; Lamiales; Lamiaceae; Nepetoideae; Mentheae; Menthinae;
OC   Mentha.
OX   NCBI_TaxID=29719;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-21; 176-200 AND 375-398,
RP   CATALYTIC ACTIVITY, AND FUNCTION.
RX   PubMed=10415126; DOI=10.1006/abbi.1999.1298;
RA   Lupien S., Karp F., Wildung M., Croteau R.;
RT   "Regiospecific cytochrome P450 limonene hydroxylases from mint (Mentha)
RT   species: cDNA isolation, characterization, and functional expression of
RT   (-)-4S-limonene-3-hydroxylase and (-)-4S-limonene-6-hydroxylase.";
RL   Arch. Biochem. Biophys. 368:181-192(1999).
RN   [2]
RP   MUTAGENESIS OF LEU-357; LEU-359; PHE-363; GLN-369 AND SER-370.
RX   PubMed=11050228; DOI=10.1073/pnas.97.22.11948;
RA   Schalk M., Croteau R.;
RT   "A single amino acid substitution (F363I) converts the regiochemistry of
RT   the spearmint (-)-limonene hydroxylase from a C6- to a C3-hydroxylase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:11948-11953(2000).
RN   [3]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=11368174; DOI=10.1006/abbi.2000.2248;
RA   Wuest M., Little D.B., Schalk M., Croteau R.;
RT   "Hydroxylation of limonene enantiomers and analogs by recombinant (-)-
RT   limonene 3- and 6-hydroxylases from mint (Mentha) species: evidence for
RT   catalysis within sterically constrained active sites.";
RL   Arch. Biochem. Biophys. 387:125-136(2001).
CC   -!- FUNCTION: Hydroxylates (-)-(4S)-limonene to (-)-trans-carveol, a
CC       precursor of (-)-carvone, responsible for the typical spearmint flavor
CC       note. Fluorinated substrate analogs are hydroxylated with the same
CC       regio- and stereochemistry. {ECO:0000269|PubMed:10415126,
CC       ECO:0000269|PubMed:11368174}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(4S)-limonene + O2 + reduced [NADPH--hemoprotein reductase] =
CC         (1S,5R)-carveol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:17945, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:15383, ChEBI:CHEBI:15389, ChEBI:CHEBI:57618,
CC         ChEBI:CHEBI:58210; EC=1.14.14.51;
CC         Evidence={ECO:0000269|PubMed:10415126, ECO:0000269|PubMed:11368174};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC       Single-pass type II membrane protein {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Mint condition - Issue 113
CC       of January 2010;
CC       URL="https://web.expasy.org/spotlight/back_issues/113";
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DR   EMBL; AF124815; AAD44150.1; -; mRNA.
DR   AlphaFoldDB; Q9XHE8; -.
DR   SMR; Q9XHE8; -.
DR   KEGG; ag:AAD44150; -.
DR   BioCyc; MetaCyc:MONOMER-15424; -.
DR   BRENDA; 1.14.14.51; 3225.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR   GO; GO:0018675; F:(S)-limonene 6-monooxygenase activity; IDA:UniProtKB.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   CDD; cd11072; CYP71-like; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 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   PANTHER; PTHR47956; CYTOCHROME P450 71B11-RELATED; 1.
DR   PANTHER; PTHR47956:SF96; CYTOCHROME P450 71B11-RELATED; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Endoplasmic reticulum; Heme; Iron; Membrane;
KW   Metal-binding; Monooxygenase; Oxidoreductase; Signal-anchor; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..496
FT                   /note="Cytochrome P450 71D18"
FT                   /id="PRO_0000389497"
FT   TRANSMEM        2..22
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
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"
FT   MUTAGEN         357
FT                   /note="L->M: No effect on regiospecificity."
FT                   /evidence="ECO:0000269|PubMed:11050228"
FT   MUTAGEN         359
FT                   /note="L->M: No effect on regiospecificity."
FT                   /evidence="ECO:0000269|PubMed:11050228"
FT   MUTAGEN         363
FT                   /note="F->I: Conversion to the regiospecificity and
FT                   catalytic efficiency of the peppermint
FT                   limonene-3-hydroxylase."
FT                   /evidence="ECO:0000269|PubMed:11050228"
FT   MUTAGEN         369
FT                   /note="Q->S: No effect on regiospecificity."
FT                   /evidence="ECO:0000269|PubMed:11050228"
FT   MUTAGEN         370
FT                   /note="S->C: No effect on regiospecificity."
FT                   /evidence="ECO:0000269|PubMed:11050228"
SQ   SEQUENCE   496 AA;  56149 MW;  06E4370F95EB91C0 CRC64;
     MELDLLSAII ILVATYIVSL LINQWRKSKS QQNLPPSPPK LPVIGHLHFL WGGLPQHVFR
     SIAQKYGPVA HVQLGEVYSV VLSSAEAAKQ AMKVLDPNFA DRFDGIGSRT MWYDKDDIIF
     SPYNDHWRQM RRICVTELLS PKNVRSFGYI RQEEIERLIR LLGSSGGAPV DVTEEVSKMS
     CVVVCRAAFG SVLKDQGSLA ELVKESLALA SGFELADLYP SSWLLNLLSL NKYRLQRMRR
     RLDHILDGFL EEHREKKSGE FGGEDIVDVL FRMQKGSDIK IPITSNCIKG FIFDTFSAGA
     ETSSTTISWA LSELMRNPAK MAKVQAEVRE ALKGKTVVDL SEVQELKYLR SVLKETLRLH
     PPFPLIPRQS REECEVNGYT IPAKTRIFIN VWAIGRDPQY WEDPDTFRPE RFDEVSRDFM
     GNDFEFIPFG AGRRICPGLH FGLANVEIPL AQLLYHFDWK LPQGMTDADL DMTETPGLSG
     PKKKNVCLVP TLYKSP
//