ID   PAXP_PENPX              Reviewed;         515 AA.
AC   Q9C449;
DT   11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   03-AUG-2022, entry version 89.
DE   RecName: Full=Cytochrome P450 monooxygenase paxP {ECO:0000303|PubMed:12884010};
DE            EC=1.-.-.- {ECO:0000305|PubMed:17428785};
DE   AltName: Full=Paxilline synthesis protein P {ECO:0000303|PubMed:11169115};
GN   Name=paxP {ECO:0000303|PubMed:11169115};
OS   Penicillium paxilli.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=70109;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC   STRAIN=PN2013;
RX   PubMed=11169115; DOI=10.1046/j.1365-2958.2001.02265.x;
RA   Young C., McMillan L., Telfer E., Scott B.;
RT   "Molecular cloning and genetic analysis of an indole-diterpene gene cluster
RT   from Penicillium paxilli.";
RL   Mol. Microbiol. 39:754-764(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=PN2013;
RX   PubMed=23949005; DOI=10.3390/toxins5081422;
RA   Scott B., Young C.A., Saikia S., McMillan L.K., Monahan B.J., Koulman A.,
RA   Astin J., Eaton C.J., Bryant A., Wrenn R.E., Finch S.C., Tapper B.A.,
RA   Parker E.J., Jameson G.B.;
RT   "Deletion and gene expression analyses define the paxilline biosynthetic
RT   gene cluster in Penicillium paxilli.";
RL   Toxins 5:1422-1446(2013).
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=12884010; DOI=10.1007/s00438-003-0887-2;
RA   McMillan L.K., Carr R.L., Young C.A., Astin J.W., Lowe R.G., Parker E.J.,
RA   Jameson G.B., Finch S.C., Miles C.O., McManus O.B., Schmalhofer W.A.,
RA   Garcia M.L., Kaczorowski G.J., Goetz M., Tkacz J.S., Scott B.;
RT   "Molecular analysis of two cytochrome P450 monooxygenase genes required for
RT   paxilline biosynthesis in Penicillium paxilli, and effects of paxilline
RT   intermediates on mammalian maxi-K ion channels.";
RL   Mol. Genet. Genomics 270:9-23(2003).
RN   [4]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=17428785; DOI=10.1074/jbc.m701626200;
RA   Saikia S., Parker E.J., Koulman A., Scott B.;
RT   "Defining paxilline biosynthesis in Penicillium paxilli: functional
RT   characterization of two cytochrome P450 monooxygenases.";
RL   J. Biol. Chem. 282:16829-16837(2007).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the ATM2 gene cluster
CC       that mediates the biosynthesis of paxilline, a mycotoxin that acts as
CC       an inhibitor of mammalian maxi-K channels (PubMed:11169115,
CC       PubMed:23949005). PaxG, the geranylgeranyl diphosphate (GGPP) synthase
CC       is proposed to catalyze the first step in paxilline biosynthesis
CC       (PubMed:23949005). Condensation of indole-3-glycerol phosphate with
CC       GGPP by paxC then forms 3-geranylgeranylindole (3-GGI), followed by
CC       epoxidation and cyclization of this intermediate (by paxM and paxB) to
CC       form paspaline (PubMed:23949005). Paspaline is subsequently converted
CC       to 13-desoxypaxilline by paxP, the latter being then converted to
CC       paxilline by paxQ (PubMed:23949005, PubMed:17428785). Finally paxilline
CC       can be mono- and di-prenylated by paxD (PubMed:23949005). PaxP can also
CC       utilized beta-paxitriol and alpha-PC-M6 as substrates converting them
CC       to paxilline (PubMed:17428785). {ECO:0000269|PubMed:11169115,
CC       ECO:0000269|PubMed:12884010, ECO:0000269|PubMed:17428785,
CC       ECO:0000269|PubMed:23949005}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:17428785, ECO:0000305|PubMed:11169115,
CC       ECO:0000305|PubMed:23949005}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of paxillines
CC       (PubMed:23949005). Leads to the accumulation of the paspaline
CC       intermediate (PubMed:12884010). {ECO:0000269|PubMed:12884010,
CC       ECO:0000269|PubMed:23949005}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; HM171111; AAK11528.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q9C449; -.
DR   SMR; Q9C449; -.
DR   KEGG; ag:AAK11528; -.
DR   BioCyc; MetaCyc:MON-18638; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:InterPro.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   GO; GO:0008152; P:metabolic process; IEA:UniProt.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   SUPFAM; SSF48264; SSF48264; 1.
PE   1: Evidence at protein level;
KW   Heme; Iron; Membrane; Metal-binding; Oxidoreductase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..515
FT                   /note="Cytochrome P450 monooxygenase paxP"
FT                   /id="PRO_0000436125"
FT   TRANSMEM        20..36
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         456
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"
SQ   SEQUENCE   515 AA;  58780 MW;  83AB34F4C0822166 CRC64;
     MDLSDFHIST PLRYFHEEAS LLWKLGVFAV LVYFLLPKPT YKTNVKVPTV KYMGPWMPEI
     LSRIFFNSHA PTVIYKGYEK FKTSAFKVVK PDGDLVVLST RYAEELRQMP STTLNALEAT
     FTDHVGGYTT ILTDSHLHTE TIQKKLTPAI GRLIPRMISE LDHAFEVEFP TCDDQFASIN
     PYTVFLRLVA RVGARIFIGD ELCREEKWLQ ASIDYTKNIF LTIALMRPMP GFLHPIVGRI
     LPSSRSLKDQ LSYIQQDLLG PVIKERRRLE ASSDSEYKKP DDFLQWMMDL AQNENESHPD
     NLSHRLLGIT SMAVVHTSAM SMTHILYDLL TMPDLIEPLR DEIRNEIKDW NKATQADLSR
     LIIMDSFLKE SQRLNPPGDL SFHRVVKKDL TLSDGLFLPK GTHICMAAGP ISKDPDVVSD
     PDTFDAFRFV KQRTATSGFV STGPNNMHFG LGRYACPGRF FAAFVIKLIL SRFLMDYDFK
     FETEHKERPK NLLIGDKIVP NVATPILIKR RATKA