ID   PSIK_PSICU              Reviewed;         362 AA.
AC   P0DPA8;
DT   25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2017, sequence version 1.
DT   03-AUG-2022, entry version 12.
DE   RecName: Full=4-hydroxytryptamine kinase {ECO:0000303|PubMed:28763571};
DE            EC=2.7.1.222 {ECO:0000269|PubMed:28763571};
DE   AltName: Full=Psilocybin biosynthesis kinase {ECO:0000303|PubMed:28763571};
GN   Name=psiK {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 [MRNA], IDENTIFICATION, FUNCTION, CATALYTIC ACTIVITY,
RP   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: 4-hydroxytryptamine kinase; 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=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:0000269|PubMed:28763571};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:28763571}.
CC   -!- SIMILARITY: Belongs to the methylthioribose kinase family.
CC       {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/";
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; KY984099; ASU62237.1; -; mRNA.
DR   AlphaFoldDB; P0DPA8; -.
DR   KEGG; ag:ASU62237; -.
DR   BRENDA; 2.7.1.222; 15552.
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; IDA:GO_Central.
DR   InterPro; IPR002575; Aminoglycoside_PTrfase.
DR   InterPro; IPR015897; CHK_kinase-like.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   Pfam; PF01636; APH; 1.
DR   SMART; SM00587; CHK; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Kinase; Nucleotide-binding; Transferase.
FT   CHAIN           1..362
FT                   /note="4-hydroxytryptamine kinase"
FT                   /id="PRO_0000442159"
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         249..251
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:O31663"
SQ   SEQUENCE   362 AA;  40442 MW;  9DBD00D508E570A3 CRC64;
     MAFDLKTEDG LITYLTKHLS LDVDTSGVKR LSGGFVNVTW RIKLNAPYQG HTSIILKHAQ
     PHMSTDEDFK IGVERSVYEY QAIKLMMANR EVLGGVDGIV SVPEGLNYDL ENNALIMQDV
     GKMKTLLDYV TAKPPLATDI ARLVGTEIGG FVARLHNIGR ERRDDPEFKF FSGNIVGRTT
     SDQLYQTIIP NAAKYGVDDP LLPTVVKDLV DDVMHSEETL VMADLWSGNI LLQLEEGNPS
     KLQKIYILDW ELCKYGPASL DLGYFLGDCY LISRFQDEQV GTTMRQAYLQ SYARTSKHSI
     NYAKVTAGIA AHIVMWTDFM QWGSEEERIN FVKKGVAAFH DARGNNDNGE ITSTLLKESS
     TA