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 .
Subcellular locations: Secreted, Lysosome, Cytoplasmic vesicle, Secretory vesicle, Acrosome
Secreted at the immunological synapse.
Primarily found in immune tissues, with the highest expression in lymph nodes and spleen (, ). Present in germinal center macrophages and inflammatory myeloid cells and antigen-presenting cells (at protein level) . Also present in spermatozoa (at protein level) . Highly expressed in primary mediastinal large B-cell lymphoma, a specific subtype of diffuse large B-cell lymphoma . Expressed by neoplastic cells of several B-cell lymphomas and by tumor-associated macrophages .