ASO_CATRO
ID ASO_CATRO Reviewed; 529 AA.
AC A0A2S1XB67;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 18-JUL-2018, sequence version 1.
DT 03-AUG-2022, entry version 15.
DE RecName: Full=O-acetylstemmadenine oxidase {ECO:0000303|PubMed:30256480};
DE Short=CrASO {ECO:0000303|PubMed:29724909, ECO:0000303|PubMed:30256480};
DE EC=1.21.3.- {ECO:0000269|PubMed:29724909, ECO:0000269|PubMed:30256480};
DE AltName: Full=Precondylocarpine acetate synthase {ECO:0000303|PubMed:29724909};
DE Flags: Precursor;
GN Name=ASO {ECO:0000303|PubMed:30256480};
GN Synonyms=PAS {ECO:0000303|PubMed:29724909};
OS Catharanthus roseus (Madagascar periwinkle) (Vinca rosea).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; lamiids; Gentianales; Apocynaceae; Rauvolfioideae; Vinceae;
OC Catharanthinae; Catharanthus.
OX NCBI_TaxID=4058;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF
RP ARG-188, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, PATHWAY, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=cv. Little Delicata;
RX PubMed=30256480; DOI=10.1111/tpj.14111;
RA Qu Y., Safonova O., De Luca V.;
RT "Completion of the canonical pathway for assembly of anticancer drugs
RT vincristine/vinblastine in Catharanthus roseus.";
RL Plant J. 97:257-266(2019).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC
RP ACTIVITY, PATHWAY, AND SUBCELLULAR LOCATION.
RC STRAIN=cv. Little Bright Eyes;
RX PubMed=29724909; DOI=10.1126/science.aat4100;
RA Caputi L., Franke J., Farrow S.C., Chung K., Payne R.M.E., Nguyen T.-D.,
RA Dang T.-T.T., Soares Teto Carqueijeiro I., Koudounas K.,
RA Duge de Bernonville T., Ameyaw B., Jones D.M., Vieira I.J.C.,
RA Courdavault V., O'Connor S.E.;
RT "Missing enzymes in the biosynthesis of the anticancer drug vinblastine in
RT Madagascar periwinkle.";
RL Science 360:1235-1239(2018).
CC -!- FUNCTION: Component of the seco-iridoid and derivatives monoterpenoid
CC indole alkaloids (MIAs, e.g. vinblastine, catharanthine, tabersonine,
CC vincadifformine, vindoline, vincristine, quinine and strychnine)
CC biosynthesis pathway. Converts O-acetylstemmadenine (OAS) to reactive
CC acetylated intermediates, likely dihydroprecondylocarpine acetate.
CC {ECO:0000269|PubMed:29724909, ECO:0000269|PubMed:30256480}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O-acetyl-15alpha-stemmadenine + O2 = H2O2 + precondylocarpine
CC acetate; Xref=Rhea:RHEA:58572, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:142673, ChEBI:CHEBI:142769;
CC Evidence={ECO:0000269|PubMed:29724909, ECO:0000269|PubMed:30256480};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58573;
CC Evidence={ECO:0000269|PubMed:29724909, ECO:0000269|PubMed:30256480};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:O64743};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:29724909,
CC ECO:0000269|PubMed:30256480}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:29724909}. Vacuole {ECO:0000269|PubMed:29724909}.
CC Vesicle {ECO:0000269|PubMed:29724909}. Note=First targeted to
CC endoplasmic reticulum (ER) and progressively secreted to vacuole by ER-
CC derived vesicles. {ECO:0000269|PubMed:29724909}.
CC -!- TISSUE SPECIFICITY: Expressed in leaf epidermis.
CC {ECO:0000269|PubMed:30256480}.
CC -!- DISRUPTION PHENOTYPE: Accumulates O-acetylstemmadenine (OAS) at the
CC expense of catharanthine and vindoline (PubMed:30256480,
CC PubMed:29724909). Strong accumulation of stemmadenine acetate
CC (PubMed:29724909). {ECO:0000269|PubMed:29724909,
CC ECO:0000269|PubMed:30256480}.
CC -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; MH136588; AYE56095.1; -; mRNA.
DR EMBL; MH213134; AWJ76616.1; -; mRNA.
DR AlphaFoldDB; A0A2S1XB67; -.
DR SMR; A0A2S1XB67; -.
DR BioCyc; MetaCyc:MON-20637; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005773; C:vacuole; IEA:UniProtKB-SubCell.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.30.43.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016167; FAD-bd_PCMH_sub1.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 1: Evidence at protein level;
KW Alkaloid metabolism; Disulfide bond; Endoplasmic reticulum; FAD;
KW Flavoprotein; Glycoprotein; Oxidoreductase; Signal; Vacuole.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..529
FT /note="O-acetylstemmadenine oxidase"
FT /id="PRO_5015696778"
FT DOMAIN 70..244
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT BINDING 102..108
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O64743"
FT BINDING 113
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O64743"
FT BINDING 168..169
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O64743"
FT BINDING 173..177
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O64743"
FT BINDING 183
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O64743"
FT BINDING 465
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O64743"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 293
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 32..92
FT /evidence="ECO:0000250|UniProtKB:O64743"
FT MUTAGEN 188
FT /note="R->W: Very low enzyme activity leading to the
FT accumulation of O-acetylstemmadenine (OAS) at the expense
FT of catharanthine, vindoline and vindorosine."
FT /evidence="ECO:0000269|PubMed:30256480"
SQ SEQUENCE 529 AA; 59214 MW; 7B362368349F3B53 CRC64;
MIKKVPIVLS IFCFLLLLSS SHGSIPEAFL NCISNKFSLD VSILNILHVP SNSSYDSVLK
STIQNPRFLK SPKPLAIITP VLHSHVQSAV ICTKQAGLQI RIRSGGADYE GLSYRSEVPF
ILLDLQNLRS ISVDIEDNSA WVESGATIGE FYHEIAQNSP VHAFPAGVSS SVGIGGHLSS
GGFGTLLRKY GLAADNIIDA KIVDARGRIL DRESMGEDLF WAIRGGGGAS FGVIVSWKVK
LVKVPPMVTV FILSKTYEEG GLDLLHKWQY IEHKLPEDLF LAVSIMDDSS SGNKTLMAGF
MSLFLGKTED LLKVMAENFP QLGLKKEDCL EMNWIDAAMY FSGHPIGESR SVLKNRESHL
PKTCVSIKSD FIQEPQSMDA LEKLWKFCRE EENSPIILML PLGGMMSKIS ESEIPFPYRK
DVIYSMIYEI VWNCEDDESS EEYIDGLGRL EELMTPYVKQ PRGSWFSTRN LYTGKNKGPG
TTYSKAKEWG FRYFNNNFKK LALIKGQVDP ENFFYYEQSI PPLHLQVEL
