GAO_TANPA
ID GAO_TANPA Reviewed; 488 AA.
AC X2JI34;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 11-JUN-2014, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=Germacrene A hydroxylase {ECO:0000303|PubMed:24704560};
DE EC=1.14.14.95 {ECO:0000269|PubMed:24704560};
DE AltName: Full=Germacrene A oxidase {ECO:0000303|PubMed:24704560};
DE Short=TpGAO {ECO:0000303|PubMed:24704560};
OS Tanacetum parthenium (Feverfew) (Matricaria parthenium).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Asterales; Asteraceae; Asteroideae; Anthemideae;
OC Anthemidinae; Tanacetum.
OX NCBI_TaxID=127999;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=24704560; DOI=10.1016/j.ymben.2014.03.005;
RA Liu Q., Manzano D., Tanic N., Pesic M., Bankovic J., Pateraki I.,
RA Ricard L., Ferrer A., de Vos R., van de Krol S., Bouwmeester H.;
RT "Elucidation and in planta reconstitution of the parthenolide biosynthetic
RT pathway.";
RL Metab. Eng. 23C:145-153(2014).
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:30468448). Component of the parthenolide
CC biosynthetic pathway; parthenolide and conjugates are promising anti-
CC cancer drugs highly active against colon cancer cells
CC (PubMed:30468448). Catalyzes three consecutive oxidations of germacrene
CC A to produce germacrene A acid (PubMed:24704560).
CC {ECO:0000269|PubMed:24704560, ECO:0000303|PubMed:30468448}.
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:24704560};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30304;
CC Evidence={ECO:0000269|PubMed:24704560};
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 floral glandular trichomes.
CC {ECO:0000269|PubMed:24704560}.
CC -!- DEVELOPMENTAL STAGE: During ovary development, accumulates until the
CC stage 3 and fades out progressively to disappear at stage 6.
CC {ECO:0000269|PubMed:24704560}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KC964544; AHN62855.1; -; mRNA.
DR AlphaFoldDB; X2JI34; -.
DR SMR; X2JI34; -.
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_0000448396"
FT TRANSMEM 7..23
FT /note="Helical; Signal-anchor for type II membrane protein"
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 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 488 AA; 55063 MW; 49F7CC426B725F55 CRC64;
MALSLTTSIA LATILFFVYK FATRSKSTKN SLPEPWRLPI IGHMHHLIGT IPHRGVMDLA
RKYGSLMHLQ LGEVSTIVVS SPKWAKEILT TYDITFANRP ETLTGEIVAY HNTDIVLAPY
GEYWRQLRKL CTLELLSVKK VKSFQSLREE ECWNLVQEIK ASGSGRPVNL SENIFKLIAT
ILSRAAFGKG IKDQKEFTEI VKEILRQTGG FDVADIFPSK KFLHHLSGKR ARLTSIHQKL
DNLINNLVAE HTVKTSSKTN ETLLDVLLRL KDSAEFPLTA DNVKAIILDM FGAGTDTSSA
TIEWAISELI KCPRAMEKVQ VELRKALNGK ERIHEEDIQE LSYLNLVIKE TLRLHPPLPL
VMPRECRQPV NLAGYDIPNK TKLIVNVFAI NRDPEYWKDA ETFIPERFEN SSTTVMGAEY
EYLPFGAGRR MCPGAALGLA NVQLPLANIL YHFNWKLPNG ASYDQIDMTE SFGATVQRKT
ELLLVPSF
