ID   T2AH_TAXCA              Reviewed;         495 AA.
AC   Q6JD68;
DT   03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2005, sequence version 2.
DT   03-AUG-2022, entry version 67.
DE   RecName: Full=Taxoid 2-alpha-hydroxylase {ECO:0000303|PubMed:15178487};
DE            EC=1.14.14.- {ECO:0000269|PubMed:15178487};
OS   Taxus canadensis (Canadian yew).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Pinopsida; Pinidae; Conifers II; Cupressales; Taxaceae;
OC   Taxus.
OX   NCBI_TaxID=88032;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RX   PubMed=15178487; DOI=10.1016/j.abb.2004.04.016;
RA   Chau M., Croteau R.;
RT   "Molecular cloning and characterization of a cytochrome P450 taxoid 2alpha-
RT   hydroxylase involved in Taxol biosynthesis.";
RL   Arch. Biochem. Biophys. 427:48-57(2004).
CC   -!- FUNCTION: Catalyzes the conversion of taxusin to 2-alpha-hydroxytaxusin
CC       in taxol biosynthesis (PubMed:15178487). Catalyzes the conversion of 7-
CC       beta-hydroxytaxusin to 2-alpha-7-beta-hydroxytaxusin in taxol
CC       biosynthesis (PubMed:15178487). {ECO:0000269|PubMed:15178487}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=O2 + reduced [NADPH--hemoprotein reductase] + taxusin =
CC         2alpha-hydroxytaxusin + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:71399, 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:63664,
CC         ChEBI:CHEBI:190505; Evidence={ECO:0000269|PubMed:15178487};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71400;
CC         Evidence={ECO:0000269|PubMed:15178487};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=7beta-hydroxytaxusin + O2 + reduced [NADPH--hemoprotein
CC         reductase] = 2alpha,7beta-dihydroxytaxusin + H(+) + H2O + oxidized
CC         [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:71407, Rhea:RHEA-
CC         COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC         ChEBI:CHEBI:58210, ChEBI:CHEBI:63665, ChEBI:CHEBI:190506;
CC         Evidence={ECO:0000269|PubMed:15178487};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71408;
CC         Evidence={ECO:0000269|PubMed:15178487};
CC   -!- PATHWAY: Alkaloid biosynthesis; taxol biosynthesis. {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:15178487};
CC       Single-pass membrane protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; AY518383; AAS89065.2; -; mRNA.
DR   SMR; Q6JD68; -.
DR   BioCyc; MetaCyc:MON-17469; -.
DR   UniPathway; UPA00842; -.
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:0042617; P:paclitaxel biosynthetic process; IEA:UniProtKB-UniPathway.
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; Oxidoreductase; Taxol biosynthesis; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..495
FT                   /note="Taxoid 2-alpha-hydroxylase"
FT                   /id="PRO_0000455980"
FT   TRANSMEM        17..37
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         441
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   495 AA;  55652 MW;  F4B7F1BF01ED52F1 CRC64;
     MDAMDLTVAK FKEFTQLQSS AILLTVVSGI IVIVILLLRS KRRSSLKLPP GKLGLPLIGE
     SLSFLWALRS NTLEQFVDKR VKKYGNVFKT SLLGQPTVVL CGAAGNRLIL SNQEKLLSRT
     VSDRVAKLTG DTSISVIAGD SHRIIRAAVA GFLGPAGLKI HIGEMSAHIR NHINQVWKGK
     DEVNVLSLAR ELVFAISASL FLNINDREEQ HQLHKTLETI LPGYFSVPIN FPGFAFRKAL
     EGNSKRRKHF SVLQEKRRRD LSVGLASRTQ DLLSVLLAYE DDKGNPLTDE EVLDNISALI
     DGSYESTSSQ MAMLLKLLSD HPECYEKVVQ EQLEIASHKK EGEEITWKDV KAMRYTWQVM
     QETLRMFAPV FGPRGKAITD IHYDGYTIPK GWQLSWATYS THQNDTYFNE PDKFMPSRFD
     EEGGRLAPYT FVPFGGGRRK CPGWEFAKTE ILLFVHHFVK TFSAYTPIDP HESIWGRPLP
     PVPANGFPIK LISRS