ID   RETO_PAPSO              Reviewed;         535 AA.
AC   P93479;
DT   20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   04-NOV-2026, entry version 114.
DE   RecName: Full=Reticuline oxidase;
DE            EC=1.21.3.3;
DE   AltName: Full=Berberine bridge-forming enzyme;
DE            Short=BBE;
DE   AltName: Full=Tetrahydroprotoberberine synthase;
DE   Flags: Precursor;
GN   Name=BBE1;
OS   Papaver somniferum (Opium poppy).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; Ranunculales; Papaveraceae; Papaveroideae;
OC   Papaver.
OX   NCBI_TaxID=3469;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY,
RP   DEVELOPMENTAL STAGE, AND INDUCTION BY ELICITOR AND METHYL JASMONATE.
RC   STRAIN=cv. Marianne;
RX   PubMed=8972604; DOI=10.1104/pp.112.4.1669;
RA   Facchini P.J., Penzes C., Johnson A.G., Bull D.;
RT   "Molecular characterization of berberine bridge enzyme genes from opium
RT   poppy.";
RL   Plant Physiol. 112:1669-1677(1996).
RN   [2]
RP   TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   PubMed=14508000; DOI=10.1105/tpc.015396;
RA   Bird D.A., Franceschi V.R., Facchini P.J.;
RT   "A tale of three cell types: alkaloid biosynthesis is localized to sieve
RT   elements in opium poppy.";
RL   Plant Cell 15:2626-2635(2003).
RN   [3]
RP   TISSUE SPECIFICITY.
RX   PubMed=15353584; DOI=10.1073/pnas.0405704101;
RA   Weid M., Ziegler J., Kutchan T.M.;
RT   "The roles of latex and the vascular bundle in morphine biosynthesis in the
RT   opium poppy, Papaver somniferum.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:13957-13962(2004).
RN   [4]
RP   DEVELOPMENTAL STAGE.
RC   STRAIN=cv. Louisiana, and cv. Marianne;
RX   PubMed=16813579; DOI=10.1111/j.1365-313x.2006.02801.x;
RA   Samanani N., Alcantara J., Bourgault R., Zulak K.G., Facchini P.J.;
RT   "The role of phloem sieve elements and laticifers in the biosynthesis and
RT   accumulation of alkaloids in opium poppy.";
RL   Plant J. 47:547-563(2006).
CC   -!- FUNCTION: Oxygen-dependent FAD-dependent oxidoreductase essential to
CC       the formation of benzophenanthridine alkaloids in the response of
CC       plants to pathogenic attack (PubMed:8972604). Catalyzes the
CC       stereospecific conversion of the N-methyl moiety of (S)-reticuline into
CC       the berberine bridge carbon of (S)-scoulerine. Involved in the
CC       biosynthesis of sanguinarine (PubMed:8972604).
CC       {ECO:0000269|PubMed:8972604}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-reticuline + O2 = (S)-scoulerine + H2O2 + H(+);
CC         Xref=Rhea:RHEA:19885, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:16240, ChEBI:CHEBI:17129, ChEBI:CHEBI:57873; EC=1.21.3.3;
CC         Evidence={ECO:0000305};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000250|UniProtKB:P30986};
CC       Note=Binds 1 FAD per subunit in a bicovalent manner.
CC       {ECO:0000250|UniProtKB:P30986};
CC   -!- COFACTOR:
CC       Name=a metal cation; Xref=ChEBI:CHEBI:25213;
CC         Evidence={ECO:0000250|UniProtKB:P30986};
CC   -!- PATHWAY: Alkaloid biosynthesis; (S)-scoulerine biosynthesis; (S)-
CC       scoulerine from (S)-reticuline: step 1/1.
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle {ECO:0000305|PubMed:8972604}.
CC       Note=Localized to the parietal region of the sieve element cytoplasm.
CC       {ECO:0000269|PubMed:14508000}.
CC   -!- TISSUE SPECIFICITY: Expressed in roots and stems (PubMed:14508000,
CC       PubMed:15353584, PubMed:8972604). Not detected in leaves or
CC       reproductive organs (PubMed:8972604). Restricted to the parietal region
CC       of sieve elements adjacent or proximal to laticifers (PubMed:14508000).
CC       {ECO:0000269|PubMed:14508000, ECO:0000269|PubMed:15353584,
CC       ECO:0000269|PubMed:8972604}.
CC   -!- DEVELOPMENTAL STAGE: Transiently induced 3 days after seed imbibition
CC       (PubMed:8972604). Increases rapidly between 1 and 3 days after seed
CC       germination (PubMed:16813579). {ECO:0000269|PubMed:16813579,
CC       ECO:0000269|PubMed:8972604}.
CC   -!- INDUCTION: Up-regulated upon fungal elicitor treatment and by methyl
CC       jasmonate. {ECO:0000269|PubMed:8972604}.
CC   -!- PTM: The FAD cofactor is bound via a bicovalent 6-S-cysteinyl, 8alpha-
CC       N1-histidyl FAD linkage. {ECO:0000250|UniProtKB:P30986}.
CC   -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC       family. {ECO:0000305}.
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DR   EMBL; AF025430; AAC61839.1; -; Genomic_DNA.
DR   PIR; T07969; T07969.
DR   AlphaFoldDB; P93479; -.
DR   SMR; P93479; -.
DR   GlyCosmos; P93479; 2 sites, No reported glycans.
DR   KEGG; ag:AAC61839; -.
DR   OMA; AKCMFFP; -.
DR   OrthoDB; 407275at2759; -.
DR   BioCyc; MetaCyc:MONOMER-20626; -.
DR   BRENDA; 1.21.3.3; 4515.
DR   UniPathway; UPA00319; UER00450.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-SubCell.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0050468; F:reticuline oxidase activity; IEA:UniProtKB-EC.
DR   Gene3D; 3.30.465.10; -; 1.
DR   Gene3D; 3.40.462.20; -; 1.
DR   Gene3D; 3.30.43.10; Uridine Diphospho-n-acetylenolpyruvylglucosamine Reductase, domain 2; 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   InterPro; IPR006093; Oxy_OxRdtase_FAD_BS.
DR   PANTHER; PTHR32448; OS08G0158400 PROTEIN; 1.
DR   Pfam; PF08031; BBE; 1.
DR   Pfam; PF01565; FAD_binding_4; 1.
DR   SUPFAM; SSF56176; FAD-binding/transporter-associated domain-like; 1.
DR   PROSITE; PS51387; FAD_PCMH; 1.
DR   PROSITE; PS00862; OX2_COVAL_FAD; 1.
PE   2: Evidence at transcript level;
KW   Alkaloid metabolism; Cytoplasmic vesicle; FAD; Flavoprotein; Glycoprotein;
KW   Oxidoreductase; Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..535
FT                   /note="Reticuline oxidase"
FT                   /id="PRO_0000020426"
FT   DOMAIN          71..245
FT                   /note="FAD-binding PCMH-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT   CARBOHYD        42
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        475
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CROSSLNK        108..170
FT                   /note="6-(S-cysteinyl)-8alpha-(pros-histidyl)-FAD (His-
FT                   Cys)"
FT                   /evidence="ECO:0000250|UniProtKB:P30986"
SQ   SEQUENCE   535 AA;  59903 MW;  F0341EF38AB41239 CRC64;
     MMCRSLTLRF FLFIVLLQTC VRGGDVNDNL LSSCLNSHGV HNFTTLSTDT NSDYFKLLHA
     SMQNPLFAKP TVSKPSFIVM PGSKEELSST VHCCTRESWT IRLRSGGHSY EGLSYTADTP
     FVIVDMMNLN RISIDVLSET AWVESGATLG ELYYAIAQST DTLGFTAGWC PTVGSGGHIS
     GGGFGMMSRK YGLAADNVVD AILIDSNGAI LDREKMGDDV FWAIRGGGGG VWGAIYAWKI
     KLLPVPEKLT VFRVTKNVGI EDASSLLHKW QYVADELDED FTVSVLGGVN GNDAWLMFLG
     LHLGRKDAAK TIIDEKFPEL GLVDKEFQEM SWGESMAFLS GLDTISELNN RFLKFDERAF
     KTKVDFTKVS VPLNVFRHAL EMLSEQPGGF IALNGFGGKM SEISTDFTPF PHRKGTKLMF
     EYIIAWNQDE ESKIGEFSEW LAKFYDYLEP FVSKEPRVGY VNHIDLDIGG IDWRNKSSTT
     NAVEIARNWG ERYFSSNYER LVKAKTLIDP NNVFNHPQSI PPMMKFEEIY MLKEL
//