Details of Drug-Metabolizing Enzyme (DME)
| General Information of DME (ID: DMEN135) | |||||
|---|---|---|---|---|---|
| DME Name | L-amino-acid oxidase (IL4I1), Homo sapiens | ||||
| Gene Name | IL4I1 | ||||
| UniProt ID | |||||
| EC Number | EC: 1.4.3.2 (Click to Show/Hide the Complete EC Tree) | ||||
| Lineage | Species: Homo sapiens (Click to Show/Hide the Complete Species Lineage) | ||||
| Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Pathway/Function) of This DME | |||||
| Sequence |
MAPLALHLLVLVPILLSLVASQDWKAERSQDPFEKCMQDPDYEQLLKVVTWGLNRTLKPQ
RVIVVGAGVAGLVAAKVLSDAGHKVTILEADNRIGGRIFTYRDQNTGWIGELGAMRMPSS HRILHKLCQGLGLNLTKFTQYDKNTWTEVHEVKLRNYVVEKVPEKLGYALRPQEKGHSPE DIYQMALNQALKDLKALGCRKAMKKFERHTLLEYLLGEGNLSRPAVQLLGDVMSEDGFFY LSFAEALRAHSCLSDRLQYSRIVGGWDLLPRALLSSLSGLVLLNAPVVAMTQGPHDVHVQ IETSPPARNLKVLKADVVLLTASGPAVKRITFSPPLPRHMQEALRRLHYVPATKVFLSFR RPFWREEHIEGGHSNTDRPSRMIFYPPPREGALLLASYTWSDAAAAFAGLSREEALRLAL DDVAALHGPVVRQLWDGTGVVKRWAEDQHSQGGFVVQPPALWQTEKDDWTVPYGRIYFAG EHTAYPHGWVETAVKSALRAAIKINSRKGPASDTASPEGHASDMEGQGHVHGVASSPSHD LAKEEGSHPPVQGQLSLQNTTHTRTSH |
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| Function | Secreted L-amino-acid oxidase that acts as a key immunoregulator . Has preference for L-aromatic amino acids: converts phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp) to phenylpyruvic acid (PP), hydroxyphenylpyruvic acid (HPP), and indole-3-pyruvic acid (I3P), respectively . Also has weak L-arginine oxidase activity . Acts as a negative regulator of anti-tumor immunity by mediating Trp degradation via an indole pyruvate pathway that activates the transcription factor AHR . IL4I1-mediated Trp catabolism generates I3P, giving rise to indole metabolites (indole-3-acetic acid (IAA) and indole-3-aldehyde (I3A)) and kynurenic acid, which act as ligands for AHR, a ligand-activated transcription factor that plays important roles in immunity and cancer . AHR activation by indoles following IL4I1-mediated Trp degradation enhances tumor progression by promoting cancer cell motility and suppressing adaptive immunity . Also has an immunoregulatory function in some immune cells, probably by mediating Trp degradation and promoting downstream AHR activation: inhibits T-cell activation and proliferation, promotes the differentiation of naive CD4(+) T-cells into FOXP3(+) regulatory T-cells (Treg) and regulates the development and function of B-cells . Also regulates M2 macrophage polarization by inhibiting T-cell activation (By similarity). Also has antibacterial properties by inhibiting growth of Gram negative and Gram positive bacteria through the production of NH4(+) and H2O2 . | ||||
| Full List of Drug(s) Metabolized by This DME | |||||
|---|---|---|---|---|---|
| Drugs in Phase 1 Clinical Trial | Click to Show/Hide the Full List of Drugs: 1 Drugs | ||||
TRP-01 |
Drug Info | Phase 1 | Depression | ICD11: 6A71 | [1] |
| Full List of Metabolic Reactions (MR) Catalyzed by This DME | ||||||||||||||||||||||||||||
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| References | |||||
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| 1 | Tryptophan and indole metabolism in immune regulation | ||||
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