Protein: 4-hydroxytryptamine kinase (P0DPA8)
Organism: Psilocybe cubensis (Psychedelic mushroom) (Stropharia cubensis)
Function: 4-hydroxytryptamine kinase; part of the gene cluster that mediates the biosynthesis of psilocybin, a psychotropic tryptamine- derived natural product. The first step in the pathway is the decarboxylation of L-tryptophan to tryptamine by the decarboxylase psiD. 4-hydroxy-L-tryptophan is accepted as substrate by psiD as well. The cytochrome P450 monooxygenase psiH then converts tryptamine to 4-hydroxytryptamine. The kinase psiK catalyzes the 4-O-phosphorylation step by converting 4-hydroxytryptamine into norbaeocystin. The methyltransferase psiM then catalyzes iterative methyl transfer to the amino group of norbaeocystin to yield psilocybin via a monomethylated intermediate, baeocystin. 4-hydroxy-6-methyl-l-tryptophancan also be converted the decarboxylase PsiD, kinase PsiK, and methyltransferase PsiM into respectively 6-methyl-norbaeocystin, 6-methylbaeocystin, and 6- methylpsilocybin. PsiK kinase can also turn psilocin into psilocybin. This activity may represent a protective mechanism to rephosphorylate the unstable psilocin to the stable psilocybin in case of intracellular ester cleavage. Moreover, psiK is able to O-phosphorylate the quaternary amine 4-hydroxy-N,N,N- trimethyltryptamine (4-OH-TMT) to yield aeruginascin, another bioactive compound found in Psilocybe species
Sequence: MAFDLKTEDGLITYLTKHLSLDVDTSGVKRLSGGFVNVTWRIKLNAPYQGHTSIILKHAQPHMSTDEDFKIGVERSVYEYQAIKLMMANREVLGGVDGIVSVPEGLNYDLENNALIMQDVGKMKTLLDYVTAKPPLATDIARLVGTEIGGFVARLHNIGRERRDDPEFKFFSGNIVGRTTSDQLYQTIIPNAAKYGVDDPLLPTVVKDLVDDVMHSEETLVMADLWSGNILLQLEEGNPSKLQKIYILDWELCKYGPASLDLGYFLGDCYLISRFQDEQVGTTMRQAYLQSYARTSKHSINYAKVTAGIAAHIVMWTDFMQWGSEEERINFVKKGVAAFHDARGNNDNGEITSTLLKESSTA
InterPro domains: - IPR002575: Aminoglycoside phosphotransferase (domain) [29-294]
- IPR015897: CHK kinase-like (domain) [115-298]
- IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [7-298]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0016773 (phosphotransferase activity, alcohol group as acceptor)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:1901564 (organonitrogen compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0006082 (organic acid metabolic process), GO:0019637 (organophosphate metabolic process), GO:0044249 (cellular biosynthetic process), GO:0006520 (amino acid metabolic process), GO:0009404 (toxin metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0006793 (phosphorus metabolic process), GO:1901566 (organonitrogen compound biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0043385 (mycotoxin metabolic process), GO:0009072 (aromatic amino acid metabolic process), GO:0009403 (toxin biosynthetic process), GO:0009821 (alkaloid biosynthetic process), GO:0043436 (oxoacid metabolic process), GO:0019438 (aromatic compound biosynthetic process), GO:0018130 (heterocycle biosynthetic process), GO:0009820 (alkaloid metabolic process), GO:0090407 (organophosphate biosynthetic process), GO:0042430 (indole-containing compound metabolic process), GO:0009308 (amine metabolic process), GO:0006796 (phosphate-containing compound metabolic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:1901605 (alpha-amino acid metabolic process), GO:0042435 (indole-containing compound biosynthetic process), GO:0019752 (carboxylic acid metabolic process), GO:0006576 (biogenic amine metabolic process), GO:0043386 (mycotoxin biosynthetic process), GO:0006586 (indolalkylamine metabolic process), GO:0006568 (tryptophan metabolic process), GO:0035835 (indole alkaloid biosynthetic process), GO:0035834 (indole alkaloid metabolic process), GO:1902221 (erythrose 4-phosphate/phosphoenolpyruvate family amino acid metabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005829 (cytosol), GO:0005622 (intracellular anatomical structure)