IL4I1
Description
The IL4I1 (interleukin 4 induced 1) is a protein-coding gene located on chromosome 19.
Secreted L-amino-acid oxidase that acts as a key immunoregulator (PubMed:17356132, PubMed:32818467, PubMed:32866000). 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 (PubMed:17356132, PubMed:32818467, PubMed:32866000). Also has weak L-arginine oxidase activity (PubMed:26673964). Acts as a negative regulator of anti-tumor immunity by mediating Trp degradation via an indole pyruvate pathway that activates the transcription factor AHR (PubMed:32818467, PubMed:32866000). 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 (PubMed:32818467, PubMed:32866000). AHR activation by indoles following IL4I1-mediated Trp degradation enhances tumor progression by promoting cancer cell motility and suppressing adaptive immunity (PubMed:32818467). 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 (PubMed:17356132, PubMed:25446972, PubMed:25778793, PubMed:28891065). 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 (PubMed:23355881). {ECO:0000250|UniProtKB:O09046, ECO:0000269|PubMed:17356132, ECO:0000269|PubMed:23355881, ECO:0000269|PubMed:25446972, ECO:0000269|PubMed:25778793, ECO:0000269|PubMed:26673964, ECO:0000269|PubMed:28891065, ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000}
IL4I1 is also known as FIG1, LAAO, LAO, hIL4I1.
Associated Diseases
- familial infantile bilateral striatal necrosis
- infantile bilateral striatal necrosis
- cancer
- isolated asymptomatic elevation of creatine phosphokinase
- 7q11.23 microduplication syndrome
- plasma fibronectin deficiency
- pentosuria
- myopathy due to calsequestrin and SERCA1 protein overload
- metabolic myopathy due to lactate transporter defect
- nonpapillary renal cell carcinoma