ID   PSIK_PSICY              Reviewed;         361 AA.
AC   A0A286LEZ6;
DT   05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT   22-NOV-2017, sequence version 1.
DT   03-AUG-2022, entry version 10.
DE   RecName: Full=4-hydroxytryptamine kinase {ECO:0000303|PubMed:28763571};
DE            EC=2.7.1.222 {ECO:0000250|UniProtKB:P0DPA8};
DE   AltName: Full=Psilocybin biosynthesis kinase {ECO:0000303|PubMed:28763571};
GN   Name=psiK {ECO:0000303|PubMed:28763571};
OS   Psilocybe cyanescens.
OC   Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC   Agaricomycetidae; Agaricales; Strophariaceae; Psilocybe.
OX   NCBI_TaxID=93625;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION, FUNCTION, AND PATHWAY.
RC   STRAIN=FSU 12416;
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).
RN   [2]
RP   FUNCTION.
RX   PubMed=30283667; DOI=10.1002/evl3.42;
RA   Reynolds H.T., Vijayakumar V., Gluck-Thaler E., Korotkin H.B.,
RA   Matheny P.B., Slot J.C.;
RT   "Horizontal gene cluster transfer increased hallucinogenic mushroom
RT   diversity.";
RL   Evol. Lett. 2:88-101(2018).
CC   -!- FUNCTION: 4-hydroxytryptamine kinase; part of the gene cluster that
CC       mediates the biosynthesis of psilocybin, a psychotropic tryptamine-
CC       derived natural product (PubMed:28763571, PubMed:30283667). The first
CC       step in the pathway is the decarboxylation of L-tryptophan to
CC       tryptamine by the decarboxylase psiD. PsiD does not decarboxylate
CC       phenylalanine, tyrosine, or 5-hydroxy- L -tryptophan (5-HTP)
CC       (PubMed:30283667). 4-hydroxy-L-tryptophan is accepted as substrate by
CC       psiD as well. The cytochrome P450 monooxygenase psiH then converts
CC       tryptamine to 4-hydroxytryptamine. The kinase psiK catalyzes the 4-O-
CC       phosphorylation step by converting 4-hydroxytryptamine into
CC       norbaeocystin. The methyltransferase psiM then catalyzes iterative
CC       methyl transfer to the amino group of norbaeocystin to yield psilocybin
CC       via a monomethylated intermediate, baeocystin. PsiK kinase can also
CC       turn psilocin into psilocybin. This activity may represent a protective
CC       mechanism to rephosphorylate the unstable psilocin to the stable
CC       psilocybin in case of intracellular ester cleavage (By similarity).
CC       {ECO:0000250|UniProtKB:P0DPA8, ECO:0000269|PubMed:28763571,
CC       ECO:0000269|PubMed:30283667}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4-hydroxytryptamine + ATP = 4-hydoxytryptamine 4-phosphate +
CC         ADP + H(+); Xref=Rhea:RHEA:55564, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:139069, ChEBI:CHEBI:139070,
CC         ChEBI:CHEBI:456216; EC=2.7.1.222;
CC         Evidence={ECO:0000250|UniProtKB:P0DPA8};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:28763571}.
CC   -!- SIMILARITY: Belongs to the methylthioribose kinase family.
CC       {ECO:0000305}.
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DR   EMBL; KY984102; ASU62240.1; -; mRNA.
DR   AlphaFoldDB; A0A286LEZ6; -.
DR   SMR; A0A286LEZ6; -.
DR   GO; GO:0140383; F:4-hydroxytryptamine kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0140380; P:psilocybin biosynthetic process; ISS:GO_Central.
DR   InterPro; IPR004119; EcKL.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   Pfam; PF02958; EcKL; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
PE   2: Evidence at transcript level;
KW   ATP-binding; Kinase; Nucleotide-binding; Transferase.
FT   CHAIN           1..361
FT                   /note="4-hydroxytryptamine kinase"
FT                   /id="PRO_0000445828"
FT   BINDING         37
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:O31663"
FT   BINDING         57
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:O31663"
FT   BINDING         118..120
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:O31663"
FT   BINDING         224
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:O31663"
FT   BINDING         248..250
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:O31663"
SQ   SEQUENCE   361 AA;  40315 MW;  F3AD5838DA19F35A CRC64;
     MTFDLKTEEG LLSYLTKHLS LDVAPNGVKR LSGGFVNVTW RVGLNAPYHG HTSIILKHAQ
     PHLSSDIDFK IGVERSAYEY QALKIVSANS SLLGSSDIRV SVPEGLHYDV VNNALIMQDV
     GTMKTLLDYV TAKPPISAEI ASLVGSQIGA FIARLHNLGR ENKDKDDFKF FSGNIVGRTT
     ADQLYQTIIP NAAKYGIDDP ILPIVVKELV EEVMNSEETL IMADLWSGNI LLQFDENSTE
     LTRIWLVDWE LCKYGPPSLD MGYFLGDCFL VARFQDQLVG TSMRQAYLKS YARNVKEPIN
     YAKATAGIGA HLVMWTDFMK WGNDEEREEF VKKGVEAFHE ANEDNRNGEI TSILVKEASR
     T