ID   T14H_TAXCU              Reviewed;         509 AA.
AC   Q84KI1;
DT   05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   03-AUG-2022, entry version 81.
DE   RecName: Full=Taxoid 14-beta-hydroxylase;
DE            EC=1.14.13.146;
DE   AltName: Full=Taxane 14b-hydroxylase;
OS   Taxus cuspidata (Japanese yew).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Pinopsida; Pinidae; Conifers II; Cupressales; Taxaceae;
OC   Taxus.
OX   NCBI_TaxID=99806;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RX   PubMed=12729625; DOI=10.1016/s0003-9861(03)00090-0;
RA   Jennewein S., Rithner C.D., Williams R.M., Croteau R.;
RT   "Taxoid metabolism: Taxoid 14beta-hydroxylase is a cytochrome P450-
RT   dependent monooxygenase.";
RL   Arch. Biochem. Biophys. 413:262-270(2003).
CC   -!- FUNCTION: Catalyzes the conversion of 5-alpha-acetoxy-10beta-ol to 5-
CC       alpha-acetoxy-10beta,14beta-dihydroxy taxadiene. Also acts on taxa-
CC       4(20),11-dien-5-alpha-yl acetate. {ECO:0000269|PubMed:12729625}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=10beta-hydroxytaxa-4(20),11-dien-5alpha-yl acetate + H(+) +
CC         NADPH + O2 = 10beta,14beta-dihydroxytaxa-4(20),11-dien-5alpha-yl
CC         acetate + H2O + NADP(+); Xref=Rhea:RHEA:31971, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:50436,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:63663;
CC         EC=1.14.13.146; Evidence={ECO:0000269|PubMed:12729625};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=33 uM for 5-alpha-acetoxy taxadiene {ECO:0000269|PubMed:12729625};
CC         KM=55 uM for 5-alpha-acetoxy-10-beta-hydroxy taxadiene
CC         {ECO:0000269|PubMed:12729625};
CC       pH dependence:
CC         Optimum pH is 7.5. {ECO:0000269|PubMed:12729625};
CC   -!- PATHWAY: Alkaloid biosynthesis; taxol biosynthesis.
CC   -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:12729625};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:12729625}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; AY188177; AAO66199.1; -; mRNA.
DR   AlphaFoldDB; Q84KI1; -.
DR   SMR; Q84KI1; -.
DR   KEGG; ag:AAO66199; -.
DR   BioCyc; MetaCyc:MON-13409; -.
DR   BRENDA; 1.14.13.146; 6225.
DR   UniPathway; UPA00842; -.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0036203; F:taxoid 14-beta-hydroxylase activity; IDA:UniProtKB.
DR   GO; GO:0042617; P:paclitaxel biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0042616; P:paclitaxel metabolic 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; Microsome;
KW   Monooxygenase; NADP; Oxidoreductase; Taxol biosynthesis; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..509
FT                   /note="Taxoid 14-beta-hydroxylase"
FT                   /id="PRO_0000418753"
FT   TRANSMEM        20..40
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        186..206
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        218..238
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         443
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   509 AA;  57147 MW;  DE7B3D2980004F15 CRC64;
     MDVFYPLKST VAKFNECFPA ILFIVLSAVA GIVLPLLLFL RSKRRSSVGL PPGKLGYPFI
     GESLLFLKAL RSNTVEQFLD ERVKNFGNVF KTSLIGHPTV VLCGPAGNRL ILANEEKLVQ
     MSWPKSSMKL MGEKSITAKR GEGHMIIRSA LQGFFSPGAL QKYIGQMSKT IENHINEKWK
     GNDQVSVVAL VGDLVFDISA CLFFNINEKH ERERLFELLE IIAVGVLAVP VDLPGFAYHR
     ALQARSKLNA ILSGLIEKRK MDLSSGLATS NQDLLSVFLT FKDDRGNPCS DEEILDNFSG
     LLHGSYDTTV SAMACVFKLL SSNPECYEKV VQEQLGILSN KLEGDEITWK DVKSMKYTWQ
     VVQETLRLYP SIFGSFRQAI TDIHYNGYII PKGWKLLWTP YTTHPKEMYF SEPEKFLPSR
     FDQEGKLVAP YTFLPFGGGQ RSCPGWEFSK MEILLSVHHF VKTFSTFTPV DPAEIIARDS
     LCPLPSNGFS VKLFPRSYSL HTGNQVKKI