ID   PSIH_PSICU              Reviewed;         508 AA.
AC   P0DPA7;
DT   25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2017, sequence version 1.
DT   03-AUG-2022, entry version 15.
DE   RecName: Full=Tryptamine 4-monooxygenase;
DE            EC=1.14.99.59 {ECO:0000269|PubMed:28763571};
DE   AltName: Full=Cytochrome P450 monooxygenase psiH {ECO:0000303|PubMed:28763571};
DE   AltName: Full=Psilocybin biosynthesis hydroxylase {ECO:0000303|PubMed:28763571};
DE   Flags: Precursor;
GN   Name=psiH {ECO:0000303|PubMed:28763571};
OS   Psilocybe cubensis (Psychedelic mushroom) (Stropharia cubensis).
OC   Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC   Agaricomycetidae; Agaricales; Strophariaceae; Psilocybe.
OX   NCBI_TaxID=181762;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, CATALYTIC
RP   ACTIVITY, AND PATHWAY.
RX   PubMed=28763571; DOI=10.1002/anie.201705489;
RA   Fricke J., Blei F., Hoffmeister D.;
RT   "Enzymatic synthesis of psilocybin.";
RL   Angew. Chem. Int. Ed. 56:12352-12355(2017).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of psilocybin, a psychotropic tryptamine-
CC       derived natural product (PubMed:28763571). The first step in the
CC       pathway is the decarboxylation of L-tryptophan to tryptamine by the
CC       decarboxylase psiD (PubMed:28763571). 4-hydroxy-L-tryptophan is
CC       accepted as substrate by psiD as well (PubMed:28763571). The cytochrome
CC       P450 monooxygenase psiH then converts tryptamine to 4-hydroxytryptamine
CC       (PubMed:28763571). The kinase psiK catalyzes the 4-O-phosphorylation
CC       step by converting 4-hydroxytryptamine into norbaeocystin
CC       (PubMed:28763571). The methyltransferase psiM then catalyzes iterative
CC       methyl transfer to the amino group of norbaeocystin to yield psilocybin
CC       via a monomethylated intermediate, baeocystin (PubMed:28763571). PsiK
CC       kinase can also turn psilocin into psilocybin (PubMed:28763571). This
CC       activity may represent a protective mechanism to rephosphorylate the
CC       unstable psilocin to the stable psilocybin in case of intracellular
CC       ester cleavage (PubMed:28763571). {ECO:0000269|PubMed:28763571}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=AH2 + O2 + tryptamine = 4-hydroxytryptamine + A + H2O;
CC         Xref=Rhea:RHEA:15865, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:57887,
CC         ChEBI:CHEBI:139069; EC=1.14.99.59;
CC         Evidence={ECO:0000269|PubMed:28763571};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:28763571}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=When the mind bends - Issue
CC       198 of December 2017;
CC       URL="https://web.expasy.org/spotlight/back_issues/198/";
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DR   EMBL; MF000993; ASU62246.1; -; Genomic_RNA.
DR   AlphaFoldDB; P0DPA7; -.
DR   SMR; P0DPA7; -.
DR   KEGG; ag:ASU62246; -.
DR   BRENDA; 1.14.99.59; 15552.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; 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:0140382; F:tryptamine 4-monooxygenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0140380; P:psilocybin biosynthetic process; IDA:GO_Central.
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   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..508
FT                   /note="Tryptamine 4-monooxygenase"
FT                   /id="PRO_0000442158"
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"
SQ   SEQUENCE   508 AA;  57515 MW;  BF9E4E5B04B86D37 CRC64;
     MIAVLFSFVI AGCIYYIVSR RVRRSRLPPG PPGIPIPFIG NMFDMPEESP WLTFLQWGRD
     YNTDILYVDA GGTEMVILNT LETITDLLEK RGSIYSGRLE STMVNELMGW EFDLGFITYG
     DRWREERRMF AKEFSEKGIK QFRHAQVKAA HQLVQQLTKT PDRWAQHIRH QIAAMSLDIG
     YGIDLAEDDP WLEATHLANE GLAIASVPGK FWVDSFPSLK YLPAWFPGAV FKRKAKVWRE
     AADHMVDMPY ETMRKLAPQG LTRPSYASAR LQAMDLNGDL EHQEHVIKNT AAEVNVGGGD
     TTVSAMSAFI LAMVKYPEVQ RKVQAELDAL TNNGQIPDYD EEDDSLPYLT ACIKELFRWN
     QIAPLAIPHK LMKDDVYRGY LIPKNTLVFA NTWAVLNDPE VYPDPSVFRP ERYLGPDGKP
     DNTVRDPRKA AFGYGRRNCP GIHLAQSTVW IAGATLLSAF NIERPVDQNG KPIDIPADFT
     TGFFRHPVPF QCRFVPRTEQ VSQSVSGP