AMO_ARTAN
ID AMO_ARTAN Reviewed; 495 AA.
AC Q1PS23; A0A0G2R041; B4YUM0; D7RD93; G4WEL3; K7PPJ8; K7ZNY4; Q0GC64; Q0GYM3;
AC Q0PIP7; Q0Z841; Q2F517; R9QHY0;
DT 21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2019, sequence version 2.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Amorpha-4,11-diene 12-monooxygenase {ECO:0000303|Ref.6};
DE EC=1.14.14.114 {ECO:0000269|PubMed:16458889, ECO:0000269|PubMed:16612385, ECO:0000269|PubMed:23246612, ECO:0000269|Ref.15};
DE AltName: Full=Amorpha-4,11-diene C-12 oxidase {ECO:0000303|PubMed:16612385, ECO:0000303|PubMed:18816428};
DE Short=Amorphadiene oxidase {ECO:0000303|PubMed:23638869};
DE AltName: Full=Cytochrome P450 71AV1 {ECO:0000303|PubMed:16612385, ECO:0000303|PubMed:18816428, ECO:0000303|Ref.6};
GN Name=CYP71AV1 {ECO:0000303|PubMed:16612385, ECO:0000303|PubMed:18816428,
GN ECO:0000303|Ref.6};
OS Artemisia annua (Sweet wormwood).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Asterales; Asteraceae; Asteroideae; Anthemideae;
OC Artemisiinae; Artemisia.
OX NCBI_TaxID=35608;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOTECHNOLOGY.
RX PubMed=16612385; DOI=10.1038/nature04640;
RA Ro D.-K., Paradise E.M., Ouellet M., Fisher K.J., Newman K.L., Ndungu J.M.,
RA Ho K.A., Eachus R.A., Ham T.S., Kirby J., Chang M.C.Y., Withers S.T.,
RA Shiba Y., Sarpong R., Keasling J.D.;
RT "Production of the antimalarial drug precursor artemisinic acid in
RT engineered yeast.";
RL Nature 440:940-943(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Olsson M.E., Teixeira M., Brodelius M., Brodelius P.E.;
RT "Amorpha-4,11-diene hydroxylase from Artemisia annua L.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Leaf;
RA Yin L.L., Yang R.Y., Zeng Q.P.;
RT "Induced expression and quantitation of artemisinin-related genes in
RT Artemisia annua L.";
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Kong J., Wang W., Cheng K.;
RT "Production of artemisinic acid by engineered yeast.";
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=cv. Feng-shun No.1;
RX PubMed=18816428; DOI=10.1055/s-2008-1081333;
RA Yang R.-Y., Feng L.-L., Yang X.-Q., Yin L.-L., Xu X.-L., Zeng Q.-P.;
RT "Quantitative transcript profiling reveals down-regulation of A sterol
RT pathway relevant gene and overexpression of artemisinin biogenetic genes in
RT transgenic Artemisia annua plants.";
RL Planta Med. 74:1510-1516(2008).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kim S.-H., Kim Y.-B., Rayhan M.U., Choi G.-E., Kim S.-U.;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Banyai W., Supaibulwatana K.;
RT "Cloning of cytochrome P450 monooxygenase (CYP71AV1) from Artemisia annua
RT L.";
RL Submitted (SEP-2010) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND INDUCTION
RP BY TRANS-CINNAMIC ACID.
RX PubMed=22986332; DOI=10.1016/j.gene.2012.09.015;
RA Misra A., Chanotiya C.S., Gupta M.M., Dwivedi U.N., Shasany A.K.;
RT "Characterization of cytochrome P450 monooxygenases isolated from trichome
RT enriched fraction of Artemisia annua L. leaf.";
RL Gene 510:193-201(2012).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, FUNCTION, AND
RP MUTAGENESIS OF SER-307; LEU-369; SER-479 AND MET-483.
RC TISSUE=Leaf;
RX PubMed=23246612; DOI=10.1016/j.febslet.2012.11.031;
RA Komori A., Suzuki M., Seki H., Nishizawa T., Marion Meyer J.J., Shimizu H.,
RA Yokoyama S., Muranaka T.;
RT "Comparative functional analysis of CYP71AV1 natural variants reveals an
RT important residue for the successive oxidation of amorpha-4,11-diene.";
RL FEBS Lett. 587:278-284(2013).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND SUBCELLULAR LOCATION.
RX PubMed=23638869; DOI=10.1111/nph.12274;
RA Ting H.-M., Wang B., Ryden A.-M., Woittiez L., van Herpen T.,
RA Verstappen F.W.A., Ruyter-Spira C., Beekwilder J., Bouwmeester H.J.,
RA van der Krol A.;
RT "The metabolite chemotype of Nicotiana benthamiana transiently expressing
RT artemisinin biosynthetic pathway genes is a function of CYP71AV1 type and
RT relative gene dosage.";
RL New Phytol. 199:352-366(2013).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Sankhuan D., Chowpongpang S., Kirdmanee C., Supaibulwatana K.;
RT "Molecular cloning of cytochrome P450 monooxygenase.";
RL Submitted (MAR-2014) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Huhao1; TISSUE=Leaf;
RX PubMed=29703587; DOI=10.1016/j.molp.2018.03.015;
RA Shen Q., Zhang L., Liao Z., Wang S., Yan T., Shi P., Liu M., Fu X., Pan Q.,
RA Wang Y., Lv Z., Lu X., Zhang F., Jiang W., Ma Y., Chen M., Hao X., Li L.,
RA Tang Y., Lv G., Zhou Y., Sun X., Brodelius P.E., Rose J.K.C., Tang K.;
RT "The genome of Artemisia annua provides insight into the evolution of
RT Asteraceae family and artemisinin biosynthesis.";
RL Mol. Plant 11:776-788(2018).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-14.
RA Yang R.Y., Zeng Q.P.;
RT "Promoter analysis of amorpha-4,11-diene monooxygenase (CYP71AV1) gene
RT involved in artemisinin biosynthesis.";
RL Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-495 (ISOFORM 1), FUNCTION, CATALYTIC
RP ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=16458889; DOI=10.1016/j.febslet.2006.01.065;
RA Teoh K.H., Polichuk D.R., Reed D.W., Nowak G., Covello P.S.;
RT "Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a
RT cytochrome P450 with a key role in the biosynthesis of the antimalarial
RT sesquiterpene lactone artemisinin.";
RL FEBS Lett. 580:1411-1416(2006).
RN [15]
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX DOI=10.1139/B09-032;
RA Teoh K.H., Polichuk D.R., Reed D.W., Covello P.S.;
RT "Molecular cloning of an aldehyde dehydrogenase implicated in artemisinin
RT biosynthesis in Artemisia annua.";
RL Botany 87:635-642(2009).
RN [16]
RP TISSUE SPECIFICITY.
RX PubMed=19664791; DOI=10.1016/j.phytochem.2009.07.009;
RA Olsson M.E., Olofsson L.M., Lindahl A.-L., Lundgren A., Brodelius M.,
RA Brodelius P.E.;
RT "Localization of enzymes of artemisinin biosynthesis to the apical cells of
RT glandular secretory trichomes of Artemisia annua L.";
RL Phytochemistry 70:1123-1128(2009).
RN [17]
RP FUNCTION.
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 [18]
RP TISSUE SPECIFICITY.
RX PubMed=21388533; DOI=10.1186/1471-2229-11-45;
RA Olofsson L., Engstroem A., Lundgren A., Brodelius P.E.;
RT "Relative expression of genes of terpene metabolism in different tissues of
RT Artemisia annua L.";
RL BMC Plant Biol. 11:45-45(2011).
RN [19]
RP INDUCTION BY GIBBERELLIC ACID.
RX DOI=10.1007/s10725-010-9510-9;
RA Banyai W., Mii M., Supaibulwatana K.;
RT "Enhancement of artemisinin content and biomass in Artemisia annua by
RT exogenous GA3 treatment.";
RL Plant Growth Regul. 63:45-54(2011).
RN [20]
RP TISSUE SPECIFICITY.
RX PubMed=22195571; DOI=10.1016/j.plantsci.2011.10.019;
RA Olofsson L., Lundgren A., Brodelius P.E.;
RT "Trichome isolation with and without fixation using laser microdissection
RT and pressure catapulting followed by RNA amplification: expression of genes
RT of terpene metabolism in apical and sub-apical trichome cells of Artemisia
RT annua L.";
RL Plant Sci. 183:9-13(2012).
RN [21]
RP BIOTECHNOLOGY.
RX PubMed=22247290; DOI=10.1073/pnas.1110740109;
RA Westfall P.J., Pitera D.J., Lenihan J.R., Eng D., Woolard F.X.,
RA Regentin R., Horning T., Tsuruta H., Melis D.J., Owens A., Fickes S.,
RA Diola D., Benjamin K.R., Keasling J.D., Leavell M.D., McPhee D.J.,
RA Renninger N.S., Newman J.D., Paddon C.J.;
RT "Production of amorphadiene in yeast, and its conversion to
RT dihydroartemisinic acid, precursor to the antimalarial agent artemisinin.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E111-E118(2012).
RN [22]
RP BIOTECHNOLOGY.
RX PubMed=23575629; DOI=10.1038/nature12051;
RA Paddon C.J., Westfall P.J., Pitera D.J., Benjamin K., Fisher K., McPhee D.,
RA Leavell M.D., Tai A., Main A., Eng D., Polichuk D.R., Teoh K.H., Reed D.W.,
RA Treynor T., Lenihan J., Fleck M., Bajad S., Dang G., Diola D., Dorin G.,
RA Ellens K.W., Fickes S., Galazzo J., Gaucher S.P., Geistlinger T., Henry R.,
RA Hepp M., Horning T., Iqbal T., Jiang H., Kizer L., Lieu B., Melis D.,
RA Moss N., Regentin R., Secrest S., Tsuruta H., Vazquez R., Westblade L.F.,
RA Xu L., Yu M., Zhang Y., Zhao L., Lievense J., Covello P.S., Keasling J.D.,
RA Reiling K.K., Renninger N.S., Newman J.D.;
RT "High-level semi-synthetic production of the potent antimalarial
RT artemisinin.";
RL Nature 496:528-532(2013).
RN [23]
RP REVIEW ON ARTEMISININ ANTIMALARIAL PROPERTIES.
RX PubMed=27488942; DOI=10.1002/anie.201601967;
RA Tu Y.;
RT "Artemisinin-A Gift from Traditional Chinese Medicine to the World (Nobel
RT Lecture).";
RL Angew. Chem. Int. Ed. 55:10210-10226(2016).
RN [24]
RP TISSUE SPECIFICITY.
RX PubMed=30851440; DOI=10.1016/j.molp.2019.02.011;
RA Judd R., Bagley M.C., Li M., Zhu Y., Lei C., Yuzuak S., Ekeloef M., Pu G.,
RA Zhao X., Muddiman D.C., Xie D.-Y.;
RT "Artemisinin biosynthesis in non-glandular trichome cells of Artemisia
RT annua.";
RL Mol. Plant 12:704-714(2019).
RN [25]
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).
RN [26]
RP BIOTECHNOLOGY.
RX PubMed=32514287; DOI=10.1186/s13020-020-00336-8;
RA Uzun T., Toptas O.;
RT "Artesunate: could be an alternative drug to chloroquine in COVID-19
RT treatment?";
RL Chin. Med. J. 15:54-54(2020).
RN [27]
RP BIOTECHNOLOGY, AND REVIEW.
RX PubMed=32405226; DOI=10.1016/j.phrs.2020.104901;
RA Cheong D.H.J., Tan D.W.S., Wong F.W.S., Tran T.;
RT "Anti-malarial drug, artemisinin and its derivatives for the treatment of
RT respiratory diseases.";
RL Pharmacol. Res. 158:104901-104901(2020).
CC -!- FUNCTION: Involved in the biosynthesis of the antimalarial endoperoxide
CC artemisinin (PubMed:16458889, PubMed:16612385, PubMed:20351109,
CC PubMed:27488942). Catalyzes three consecutive oxidations of amorpha-
CC 4,11-diene to produce artemisinic acid, with artemisinic alcohol and
CC artemisinic aldehyde as intermediates products, but is unable to
CC oxidize germacrene A (PubMed:16458889, PubMed:16612385,
CC PubMed:20351109, PubMed:23246612). No activity with limonene, alpha-
CC pinene, beta-pinene, pinocarveol, (-)-alloisolongifolene,
CC caryophyllene, (-)-alpha-gurjunene, (+)-gamma-gurjunene, (+)-ledene,
CC (+)-beta-selinene and (+)-valencene as substrates (PubMed:16458889,
CC PubMed:16612385, PubMed:20351109). {ECO:0000269|PubMed:16458889,
CC ECO:0000269|PubMed:16612385, ECO:0000269|PubMed:20351109,
CC ECO:0000269|PubMed:23246612, ECO:0000303|PubMed:27488942}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-amorpha-4,11-diene + 3 O2 + 3 reduced [NADPH--hemoprotein
CC reductase] = (+)-artemisinate + 4 H(+) + 4 H2O + 3 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:32999, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:52026, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:64782; EC=1.14.14.114;
CC Evidence={ECO:0000269|PubMed:16458889, ECO:0000269|PubMed:16612385,
CC ECO:0000269|PubMed:23246612, ECO:0000269|Ref.15};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33000;
CC Evidence={ECO:0000269|PubMed:16458889, ECO:0000269|PubMed:16612385,
CC ECO:0000269|PubMed:23246612, ECO:0000269|Ref.15};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=0.04 nmol/min/mg enzyme with artemisinic alcohol as substrate
CC {ECO:0000269|Ref.15};
CC Vmax=0.02 nmol/min/mg enzyme with dihydroartemisinic alcohol as
CC substrate {ECO:0000269|Ref.15};
CC Vmax=0.510 nmol/min/mg enzyme with artemisinic aldehyde as substrate
CC {ECO:0000269|Ref.15};
CC -!- PATHWAY: Sesquiterpene biosynthesis. {ECO:0000303|PubMed:30468448}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23638869}; Single-pass type II membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=AMOLAP {ECO:0000303|PubMed:23638869};
CC IsoId=Q1PS23-1; Sequence=Displayed;
CC Name=2; Synonyms=AMOHAP {ECO:0000303|PubMed:23638869};
CC IsoId=Q1PS23-2; Sequence=VSP_060270;
CC -!- TISSUE SPECIFICITY: Highly expressed both in apical and sub-apical
CC cells of glandular secretory trichomes (PubMed:22195571,
CC PubMed:19664791). Detected in flower buds, leaves and roots
CC (PubMed:22986332). Also present in non-glandular trichome cells
CC (PubMed:30851440). {ECO:0000269|PubMed:16458889,
CC ECO:0000269|PubMed:19664791, ECO:0000269|PubMed:21388533,
CC ECO:0000269|PubMed:22195571, ECO:0000269|PubMed:22986332,
CC ECO:0000269|PubMed:30851440}.
CC -!- INDUCTION: Strongly induced by gibberellic acid (GA(3)) leading to an
CC increased artemisinin yield (Ref.19). Accumulates in the presence of
CC trans-cinnamic acid (PubMed:22986332). {ECO:0000269|PubMed:22986332,
CC ECO:0000269|Ref.19}.
CC -!- BIOTECHNOLOGY: Artemisinin and derivatives (e.g. artesunate), are
CC antimalarial drugs due to their endoperoxidase properties; they also
CC display multiple pharmacological actions against inflammation,viral
CC infections, and cell and tumor proliferation (PubMed:32514287,
CC PubMed:32405226). Artesunate may be a promising treatment for COVID-19
CC mediated by the severe acute respiratory syndrome coronavirus 2 (2019-
CC nCoV) (SARS-CoV-2) because of its anti-inflammatory activity, NF-kappaB
CC (nuclear factor kappa B)-coronavirus effect and chloroquine-like
CC endocytosis inhibition mechanism (PubMed:32514287, PubMed:32405226).
CC {ECO:0000303|PubMed:32405226, ECO:0000303|PubMed:32514287}.
CC -!- BIOTECHNOLOGY: Yeast (S.cerevisiae) has been engineered to produce
CC artemisinic-acid, a precursor of the antimalarial artemisinin compound,
CC by expressing AMS1/ADS, CYP71AV1, ADH1 and ALDH1 in conjunction with
CC CYB5 and CPR1. {ECO:0000269|PubMed:16612385,
CC ECO:0000269|PubMed:22247290, ECO:0000269|PubMed:23575629}.
CC -!- MISCELLANEOUS: [Isoform 2]: Reduced production of artemisinic acid (AA)
CC but increased accumulation of artemisinic alcohol (AAOH) and
CC artemisinic aldehyde (AAA), and production of (DHAA) probably due to a
CC lower catalytic activity. {ECO:0000269|PubMed:23638869}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABC41927.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=ABG49365.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; DQ268763; ABB82944.1; -; mRNA.
DR EMBL; DQ453967; ABE57266.1; -; mRNA.
DR EMBL; DQ826743; ABG91755.1; -; Genomic_DNA.
DR EMBL; EF197889; ABM88788.1; -; mRNA.
DR EMBL; DQ872632; ABI31728.1; -; mRNA.
DR EMBL; EU684540; ACF74516.1; -; mRNA.
DR EMBL; HQ315834; ADU25498.1; -; mRNA.
DR EMBL; JN594504; AFO64615.1; -; mRNA.
DR EMBL; AB706288; BAM68808.1; -; mRNA.
DR EMBL; JQ254992; AFP19100.1; -; mRNA.
DR EMBL; KJ609178; AIC83779.1; -; mRNA.
DR EMBL; PKPP01014078; PWA40082.1; -; Genomic_DNA.
DR EMBL; HM048927; ADI24872.1; -; Genomic_DNA.
DR EMBL; DQ667170; ABG49365.1; ALT_INIT; Genomic_DNA.
DR EMBL; DQ315671; ABC41927.1; ALT_INIT; mRNA.
DR AlphaFoldDB; Q1PS23; -.
DR SMR; Q1PS23; -.
DR STRING; 35608.Q1PS23; -.
DR KEGG; ag:ABB82944; -.
DR BRENDA; 1.14.13.158; 7150.
DR BRENDA; 1.14.14.114; 7150.
DR Proteomes; UP000245207; Unassembled WGS sequence.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
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:0062150; F:amorpha-4,11-diene 12-monooxygenase 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:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0051762; P:sesquiterpene biosynthetic 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 Alternative initiation; Endoplasmic reticulum; Glycoprotein; Heme; Iron;
KW Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..495
FT /note="Amorpha-4,11-diene 12-monooxygenase"
FT /id="PRO_0000412767"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..29
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..495
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT BINDING 439
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 SITE 479
FT /note="Required for artemisinic alcohol oxidizing activity
FT that catalyzes the conversion of artemisinic alcohol to
FT artemisinic aldehyde"
FT /evidence="ECO:0000269|PubMed:23246612"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 386
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 1..7
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305|PubMed:23638869"
FT /id="VSP_060270"
FT MUTAGEN 307
FT /note="S->A: Reduced activity leading to a slightly reduced
FT accumulation of artemisinic acid."
FT /evidence="ECO:0000269|PubMed:23246612"
FT MUTAGEN 369
FT /note="L->M: Reduced activity leading to a reduced
FT accumulation of artemisinic acid."
FT /evidence="ECO:0000269|PubMed:23246612"
FT MUTAGEN 479
FT /note="S->F: Altered artemisinic alcohol oxidizing activity
FT leading to the accumulation of artemisinic alcohol."
FT /evidence="ECO:0000269|PubMed:23246612"
FT MUTAGEN 483
FT /note="M->V: Reduced activity leading to a reduced
FT accumulation of artemisinic acid."
FT /evidence="ECO:0000269|PubMed:23246612"
FT CONFLICT 27
FT /note="K -> E (in Ref. 6; ACF74516)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="G -> R (in Ref. 8; AFO64615)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="R -> G (in Ref. 6; ACF74516)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="I -> V (in Ref. 5; ABI31728)"
FT /evidence="ECO:0000305"
FT CONFLICT 102..103
FT /note="SF -> TS (in Ref. 7; ADU25498 and 11; AIC83779)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="S -> T (in Ref. 1; ABB82944, 3; ABG91755, 5;
FT ABI31728, 14; ABC41927, 2; ABE57266, 10; AFP19100 and 8;
FT AFO64615)"
FT CONFLICT 140
FT /note="L -> S (in Ref. 6; ACF74516)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="V -> I (in Ref. 14; ABC41927 and 3; ABG91755)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="I -> T (in Ref. 6; ACF74516)"
FT /evidence="ECO:0000305"
FT CONFLICT 314
FT /note="S -> P (in Ref. 5; ABI31728)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="M -> L (in Ref. 3; ABG91755)"
FT /evidence="ECO:0000305"
FT CONFLICT 467
FT /note="G -> D (in Ref. 4; ABG49365/ABM88788)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="T -> A (in Ref. 5; ABI31728 and 10; AFP19100)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 495 AA; 55711 MW; F4B6D33FD1E1BBA7 CRC64;
MKSILKAMAL SLTTSIALAT ILLFVYKFAT RSKSTKKSLP EPWRLPIIGH MHHLIGTTPH
RGVRDLARKY GSLMHLQLGE VPTIVVSSPK WAKEILTTYD ISFANRPETL TGEIVLYHNT
DVVLAPYGEY WRQLRKICTL ELLSVKKVKS FQSLREEECW NLVQEIKASG SGRPVNLSEN
VFKLIATILS RAAFGKGIKD QKELTEIVKE ILRQTGGFDV ADIFPSKKFL HHLSGKRARL
TSLRKKIDNL IDNLVAEHTV NTSSKTNETL LDVLLRLKDS AEFPLTSDNI KAIILDMFGA
GTDTSSSTIE WAISELIKCP KAMEKVQAEL RKALNGKEKI HEEDIQELSY LNMVIKETLR
LHPPLPLVLP RECRQPVNLA GYNIPNKTKL IVNVFAINRD PEYWKDAEAF IPERFENSSA
TVMGAEYEYL PFGAGRRMCP GAALGLANVQ LPLANILYHF NWKLPNGVSY DQIDMTESSG
ATMQRKTELL LVPSF
