ID   C71DC_CATRO             Reviewed;         506 AA.
AC   P98183; C0KYN4;
DT   13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT   10-MAY-2017, sequence version 2.
DT   02-SEP-2026, entry version 103.
DE   RecName: Full=Tabersonine 16-hydroxylase 1 {ECO:0000303|PubMed:24108213};
DE            EC=1.14.14.103 {ECO:0000269|PubMed:12228585, ECO:0000269|PubMed:24108213};
DE   AltName: Full=Cytochrome P450 71D12 {ECO:0000303|PubMed:24108213};
GN   Name=CYP71D12 {ECO:0000303|PubMed:24108213};
GN   Synonyms=T16H1 {ECO:0000303|PubMed:24108213};
OS   Catharanthus roseus (Madagascar periwinkle) (Vinca rosea).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   asterids; lamiids; Gentianales; Apocynaceae; Rauvolfioideae; Vinceae;
OC   Catharanthinae; Catharanthus.
OX   NCBI_TaxID=4058;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX   PubMed=21047699; DOI=10.1016/j.jplph.2010.08.018;
RA   Guirimand G., Guihur A., Poutrain P., Hericourt F., Mahroug S.,
RA   St-Pierre B., Burlat V., Courdavault V.;
RT   "Spatial organization of the vindoline biosynthetic pathway in Catharanthus
RT   roseus.";
RL   J. Plant Physiol. 168:549-557(2011).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 12-506, AND FUNCTION.
RX   PubMed=10481044; DOI=10.1016/s0014-5793(99)01138-2;
RA   Schroeder G., Unterbusch E., Kaltenbach M., Schmidt J., Strack D.,
RA   Schroeder J.;
RT   "Light-induced cytochrome P450-dependent enzyme in indole alkaloid
RT   biosynthesis: tabersonine 16-hydroxylase.";
RL   FEBS Lett. 458:97-102(1999).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP   LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RX   PubMed=12228585; DOI=10.1104/pp.109.1.131;
RA   St Pierre B., De Luca V.;
RT   "A cytochrome P-450 monooxygenase catalyzes the first step in the
RT   conversion of tabersonine to vindoline in Catharanthus roseus.";
RL   Plant Physiol. 109:131-139(1995).
RN   [4]
RP   TISSUE SPECIFICITY.
RX   PubMed=16262708; DOI=10.1111/j.1365-313x.2005.02557.x;
RA   Murata J., De Luca V.;
RT   "Localization of tabersonine 16-hydroxylase and 16-OH tabersonine-16-O-
RT   methyltransferase to leaf epidermal cells defines them as a major site of
RT   precursor biosynthesis in the vindoline pathway in Catharanthus roseus.";
RL   Plant J. 44:581-594(2005).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP   SPECIFICITY, AND INDUCTION BY METHYL JASMONATE.
RX   PubMed=24108213; DOI=10.1104/pp.113.222828;
RA   Besseau S., Kellner F., Lanoue A., Thamm A.M., Salim V., Schneider B.,
RA   Geu-Flores F., Hoefer R., Guirimand G., Guihur A., Oudin A., Glevarec G.,
RA   Foureau E., Papon N., Clastre M., Giglioli-Guivarc'h N., St-Pierre B.,
RA   Werck-Reichhart D., Burlat V., De Luca V., O'Connor S.E., Courdavault V.;
RT   "A pair of tabersonine 16-hydroxylases initiates the synthesis of vindoline
RT   in an organ-dependent manner in Catharanthus roseus.";
RL   Plant Physiol. 163:1792-1803(2013).
CC   -!- FUNCTION: Involved in the flower biosynthesis of vindoline, a precursor
CC       of vinblastine and vincristine (PubMed:10481044, PubMed:12228585,
CC       PubMed:24108213). Hydroxylates specifically tabersonine, 2,3-
CC       dihydrotabersonine and 2,3-dihydro-3-hydroxytabersonine, but has no
CC       activity with naringenin, tryptamine, secologanin, strictosidine,
CC       ajmalicine, vindoline and catharanthine (PubMed:24108213).
CC       {ECO:0000269|PubMed:10481044, ECO:0000269|PubMed:12228585,
CC       ECO:0000269|PubMed:24108213}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(-)-tabersonine + reduced [NADPH--hemoprotein reductase] + O2
CC         = 16-hydroxytabersonine + oxidized [NADPH--hemoprotein reductase] +
CC         H2O + H(+); Xref=Rhea:RHEA:14133, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:57618, ChEBI:CHEBI:57893, ChEBI:CHEBI:58210,
CC         ChEBI:CHEBI:58239; EC=1.14.14.103;
CC         Evidence={ECO:0000269|PubMed:12228585, ECO:0000269|PubMed:24108213};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:Q96242};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=11 uM for tabersonine in a T16H/16OMT coupled system
CC         {ECO:0000269|PubMed:12228585};
CC         KM=350 nM for tabersonine {ECO:0000269|PubMed:24108213};
CC         KM=14 uM for NADPH in a T16H/16OMT coupled system
CC         {ECO:0000269|PubMed:12228585};
CC         Note=concentrations of tabersonine greater than 30 uM are inhibitory.
CC         {ECO:0000269|PubMed:12228585};
CC       pH dependence:
CC         Optimum pH is 7.5 in phosphate buffer and 8.0 in TRIS-HCl.
CC         {ECO:0000269|PubMed:12228585};
CC       Temperature dependence:
CC         Stable at 30 degrees Celsius. {ECO:0000269|PubMed:12228585};
CC   -!- PATHWAY: Alkaloid biosynthesis; vindoline biosynthesis. {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:12228585, ECO:0000269|PubMed:21047699}; Single-pass
CC       membrane protein {ECO:0000255}. Note=The ER localization is dependent
CC       on the presence of the putative transmembrane helix.
CC       {ECO:0000269|PubMed:21047699}.
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in young leaves of mature
CC       plants (PubMed:12228585, PubMed:16262708). Low expression in roots and
CC       flowers, but not detected in stems and old leaves (PubMed:12228585,
CC       PubMed:16262708). Found predominantly in leaf epidermis
CC       (PubMed:12228585, PubMed:16262708). Barely detected in roots,
CC       internodes, young and mature leaves, and flower buds, but relatively
CC       abundant in fully developed flowers (PubMed:24108213). Not detected in
CC       leaf epidermal cells (PubMed:24108213). {ECO:0000269|PubMed:12228585,
CC       ECO:0000269|PubMed:16262708, ECO:0000269|PubMed:24108213}.
CC   -!- DEVELOPMENTAL STAGE: Peak of expression after light treatment at 9 days
CC       of seedling development. {ECO:0000269|PubMed:12228585}.
CC   -!- INDUCTION: Up-regulated by methyl jasmonate (PubMed:24108213).
CC       Inhibited by cytochrome c, CO, clotrimazole, miconazole, tricliphane,
CC       flusilazole and tetcyclasis, and with a lower efficiency, by 1-
CC       phenylimidazole and piperonylbutoxide. Not inhibited by potassium
CC       cyanide and sodium azide. {ECO:0000269|PubMed:12228585,
CC       ECO:0000269|PubMed:24108213}.
CC   -!- MISCELLANEOUS: Tabersonine 16-hydroxylation is orchestrated in an
CC       organ-dependent manner by two genes including CYP71D351, which encodes
CC       the T16H2 isoform acting in the foliar vindoline biosynthesis, and
CC       CYP71D12, which encodes the T16H1 isoform acting in the flower
CC       vindoline biosynthesis. {ECO:0000269|PubMed:24108213}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; FJ647194; ACM92061.1; -; mRNA.
DR   EMBL; AJ238612; CAB56503.1; -; mRNA.
DR   AlphaFoldDB; P98183; -.
DR   SMR; P98183; -.
DR   KEGG; ag:CAB56503; -.
DR   OrthoDB; 2789670at2759; -.
DR   BioCyc; MetaCyc:MONOMER-7709; -.
DR   BRENDA; 1.14.14.103; 1211.
DR   SABIO-RK; P98183; -.
DR   UniPathway; UPA00365; -.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; EXP:UniProtKB.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0050594; F:tabersonine 16-hydroxylase activity; EXP:UniProtKB.
DR   GO; GO:0009821; P:alkaloid biosynthetic process; IEA:UniProtKB-ARBA.
DR   GO; GO:0035834; P:indole alkaloid metabolic process; IEA:UniProtKB-ARBA.
DR   CDD; cd11072; CYP71-like; 1.
DR   FunFam; 1.10.630.10:FF:000043; Cytochrome P450 99A2; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR   InterPro; IPR052306; CYP450_71D.
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; PTHR47953:SF19; OS06G0641600 PROTEIN; 1.
DR   PANTHER; PTHR47953; OS08G0105600 PROTEIN; 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   Alkaloid metabolism; Endoplasmic reticulum; Heme; Iron; Membrane;
KW   Metal-binding; Monooxygenase; Oxidoreductase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..506
FT                   /note="Tabersonine 16-hydroxylase 1"
FT                   /id="PRO_0000310728"
FT   TRANSMEM        1..21
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         447
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   506 AA;  58079 MW;  485FF14E6D34901B CRC64;
     MEFYYFLYLA FLLFCFILSK TTKKFGQNSQ YSNHDELPPG PPQIPILGNA HQLSGGHTHH
     ILRDLAKKYG PLMHLKIGEV STIVASSPQI AEEIFRTHDI LFADRPSNLE SFKIVSYDFS
     DMVVSPYGNY WRQLRKISMM ELLSQKSVQS FRSIREEEVL NFIKSIGSKE GTRINLSKEI
     SLLIYGITTR AAFGEKNKNT EEFIRLLDQL TKAVAEPNIA DMFPSLKFLQ LISTSKYKIE
     KIHKQFDVIV ETILKGHKEK INKPLSQENG EKKEDLVDVL LNIQRRNDFE APLGDKNIKA
     IIFNIFSAGT ETSSTTVDWA MCEMIKNPTV MKKAQEEVRK VFNEEGNVDE TKLHQLKYLQ
     AVIKETLRLH PPVPLLLPRE CREQCKIKGY TIPSKSRVIV NAWAIGRDPN YWIEPEKFNP
     DRFLESKVDF KGNSFEYLPF GGGRRICPGI TFALANIELP LAQLLFHFDW QSNTEKLNMK
     ESRGVTVRRE DDLYLTPVNF SSSSPA
//