GAO_HELAN
ID GAO_HELAN Reviewed; 488 AA.
AC D5JBX0;
DT 21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT 15-JUN-2010, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=Germacrene A hydroxylase {ECO:0000303|PubMed:20351109};
DE EC=1.14.14.95 {ECO:0000269|PubMed:20351109};
DE AltName: Full=Germacrene A oxidase {ECO:0000303|PubMed:20351109};
DE Short=HaGAO {ECO:0000303|PubMed:20351109};
GN Name=GAO {ECO:0000303|PubMed:20351109};
OS Helianthus annuus (Common sunflower).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Asterales; Asteraceae; Asteroideae;
OC Heliantheae alliance; Heliantheae; Helianthus.
OX NCBI_TaxID=4232;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20351109; DOI=10.1074/jbc.m110.111757;
RA Nguyen D.T., Goepfert J.C., Ikezawa N., Macnevin G., Kathiresan M.,
RA Conrad J., Spring O., Ro D.-K.;
RT "Biochemical conservation and evolution of germacrene A oxidase in
RT asteraceae.";
RL J. Biol. Chem. 285:16588-16598(2010).
RN [2]
RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=29758164; DOI=10.1021/acschembio.8b00126;
RA Frey M., Schmauder K., Pateraki I., Spring O.;
RT "Biosynthesis of eupatolide-A metabolic route for sesquiterpene lactone
RT formation involving the P450 enzyme CYP71DD6.";
RL ACS Chem. Biol. 13:1536-1543(2018).
RN [3]
RP PATHWAY, AND REVIEW.
RX PubMed=30468448; DOI=10.1039/c8np00077h;
RA Liu Y., Jing S.-X., Luo S.-H., Li S.-H.;
RT "Non-volatile natural products in plant glandular trichomes: chemistry,
RT biological activities and biosynthesis.";
RL Nat. Prod. Rep. 36:626-665(2019).
CC -!- FUNCTION: Involved in the biosynthesis of germacrene-derived
CC sesquiterpene lactones (PubMed:20351109). Catalyzes three consecutive
CC oxidations of germacrene A to produce germacrene A acid
CC (PubMed:20351109). Could also catalyze the three-step oxidation of non-
CC natural substrate amorphadiene to artemisinic acid (PubMed:20351109).
CC {ECO:0000269|PubMed:20351109}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-(R)-germacrene A + 3 O2 + 3 reduced [NADPH--hemoprotein
CC reductase] = germacra-1(10),4,11(13)-trien-12-oate + 4 H(+) + 4 H2O +
CC 3 oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:30303,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:41595,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:61301;
CC EC=1.14.14.95; Evidence={ECO:0000269|PubMed:20351109};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30304;
CC Evidence={ECO:0000269|PubMed:20351109};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000303|PubMed:30468448}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:D5JBW8}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:D5JBW8}.
CC -!- TISSUE SPECIFICITY: Expressed in leaf primordia.
CC {ECO:0000269|PubMed:29758164}.
CC -!- DEVELOPMENTAL STAGE: In developing leaves, expressed at very low levels
CC in young leaf primordia, but strongly induced after the fourth and
CC fifth days following leaf primordia initiation.
CC {ECO:0000269|PubMed:29758164}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; GU256646; ADF43082.1; -; mRNA.
DR AlphaFoldDB; D5JBX0; -.
DR SMR; D5JBX0; -.
DR EnsemblPlants; mRNA:HanXRQr2_Chr13g0583041; mRNA:HanXRQr2_Chr13g0583041; HanXRQr2_Chr13g0583041.
DR Gramene; mRNA:HanXRQr2_Chr13g0583041; mRNA:HanXRQr2_Chr13g0583041; HanXRQr2_Chr13g0583041.
DR OMA; NPAIMGK; -.
DR OrthoDB; 702827at2759; -.
DR BRENDA; 1.14.14.95; 2597.
DR UniPathway; UPA00213; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0106223; F:germacrene A hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0051762; P:sesquiterpene biosynthetic process; IDA:UniProtKB.
DR GO; GO:0016114; P:terpenoid 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; Glycoprotein; Heme; Iron; Membrane; Metal-binding;
KW Monooxygenase; Oxidoreductase; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..488
FT /note="Germacrene A hydroxylase"
FT /id="PRO_0000412766"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..23
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 24..488
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT BINDING 432
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:P04798"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 260
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 412
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 488 AA; 55088 MW; 01ADF6F5776D8471 CRC64;
MEVSLTTSIA LATIVFFLYK LLTRPTSSKN RLPEPWRLPI IGHMHHLIGT MPHRGVMDLA
RKYGSLMHLQ LGEVSAIVVS SPKWAKEILT TYDIPFANRP ETLTGEIIAY HNTDIVLAPY
GEYWRQLRKL CTLELLSVKK VKSFQSLREE ECWNLVQEIK ASGSGTPFNL SEGIFKVIAT
VLSRAAFGKG IKDQKQFTEI VKEILRETGG FDVADIFPSK KFLHHLSGKR GRLTSIHNKL
DSLINNLVAE HTVSKSSKVN ETLLDVLLRL KNSEEFPLTA DNVKAIILDM FGAGTDTSSA
TVEWAISELI RCPRAMEKVQ AELRQALNGK ERIKEEEIQD LPYLNLVIRE TLRLHPPLPL
VMPRECRQAM NLAGYDVANK TKLIVNVFAI NRDPEYWKDA ESFNPERFEN SNTTIMGADY
EYLPFGAGRR MCPGSALGLA NVQLPLANIL YYFKWKLPNG ASHDQLDMTE SFGATVQRKT
ELMLVPSF
