GAO_LACSA
ID GAO_LACSA Reviewed; 488 AA.
AC D5J9U8;
DT 21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT 15-JUN-2010, sequence version 1.
DT 03-AUG-2022, entry version 44.
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=LsGAO {ECO:0000303|PubMed:20351109};
GN Name=GAO1 {ECO:0000303|PubMed:20351109};
OS Lactuca sativa (Garden lettuce).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Asterales; Asteraceae; Cichorioideae; Cichorieae;
OC Lactucinae; Lactuca.
OX NCBI_TaxID=4236;
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 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 -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; GU198171; ADF32078.1; -; mRNA.
DR AlphaFoldDB; D5J9U8; -.
DR SMR; D5J9U8; -.
DR KEGG; ag:ADF32078; -.
DR BioCyc; MetaCyc:MON-15751; -.
DR BRENDA; 1.14.14.95; 2910.
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_0000412765"
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"
SQ SEQUENCE 488 AA; 54963 MW; 7A2C86F88E9812B2 CRC64;
MELSITTSIA LATIVFFLYK LATRPKSTKK QLPEASRLPI IGHMHHLIGT MPHRGVMDLA
RKHGSLMHLQ LGEVSTIVVS SPKWAKEILT TYDITFANRP ETLTGEIIAY HNTDIVLAPY
GEYWRQLRKL CTLELLSVKK VKSFQSIREE ECWNLVKEVK ESGSGKPINL SESIFTMIAT
ILSRAAFGKG IKDQREFTEI VKEILRQTGG FDVADIFPSK KFLHHLSGKR ARLTSIHKKL
DNLINNIVAE HHVSTSSKAN ETLLDVLLRL KDSAEFPLTA DNVKAIILDM FGAGTDTSSA
TVEWAISELI RCPRAMEKVQ AELRQALNGK EKIQEEDIQD LAYLNLVIRE TLRLHPPLPL
VMPRECREPV NLAGYEIANK TKLIVNVFAI NRDPEYWKDA EAFIPERFEN NPNNIMGADY
EYLPFGAGRR MCPGAALGLA NVQLPLANIL YHFNWKLPNG ASHDQLDMTE SFGATVQRKT
ELLLVPSF
