IL4I1 (Vector pENTR223.1, Accession No. BC090852)

Length: 1704 Sequence: ATGGCCCCAT TGGCCCTGCA CCTCCTCGTC CTCGTCCCCA TCCTCCTCAG CCTGGTGGCC TCCCAGGACT GGAAGGCTGA ACGCAGCCAA GACCCCTTCG AGAAATGCAT GCAGGATCCT GACTATGAGC AGCTGCTCAA GGTGGTGACC TGGGGGCTCA ATCGGACCCT GAAGCCCCAG AGGGTGATTG TGGTTGGCGC TGGTGTGGCC GGGCTGGTGG CCGCCAAGGT GCTCAGCGAT GCTGGACACA AGGTCACCAT CCTGGAGGCA GATAACAGGA TCGGGGGCCG CATCTTCACC TACCGGGACC AGAACACGGG CTGGATTGGG GAGCTGGGAG CCATGCGCAT GCCCAGCTCT CACAGGATCC TCCACAAGCT CTGCCAGGGC CTGGGGCTCA ACCTGACCAA GTTCACCCAG TACGACAAGA ACACGTGGAC GGAGGTGCAC GAAGTGAAGC TGCGCAACTA TGTGGTGGAG AAGGTGCCCG AGAAGCTGGG CTACGCCTTG CGTCCCCAGG AAAAGGGCCA CTCGCCCGAA GACATCTACC AGATGGCTCT CAACCAGGCC CTCAAAGACC TCAAGGCACT GGGCTGCAGA AAGGCGATGA AGAAGTTTGA AAGGCACACG CTCTTGGAAT ATCTTCTCGG GGAGGGGAAC CTGAGCCGGC CGGCCGTGCA GCTTCTGGGA GACGTGATGT CCGAGGATGG CTTCTTCTAT CTCAGCTTCG CCGAGGCCCT CCGGGCCCAC AGCTGCCTCA GCGACAGACT CCAGTACAGC CGCATCGTGG GTGGCTGGGA CCTGCTGCCG CGCGCGCTGC TGAGCTCGCT GTCCGGGCTT GTGCTGTTGA ACGCGCCCGT GGTGGCGATG ACCCAGGGAC CGCACGATGT GCACGTGCAG ATCGAGACCT CTCCCCCGGC GCGGAATCTG AAGGTGCTGA AGGCCGACGT GGTGCTGCTG ACGGCGAGCG GACCGGCGGT GAAGCGCATC ACCTTCTCGC CGCCGCTGCC CCGCCACATG CAGGAGGCGC TGCGGAGGCT GCACTACGTG CCGGCCACCA AGGTGTTCCT AAGCTTCCGC AGGCCCTTCT GGCGCGAGGA GCACATTGAA GGCGGCCACT CAAACACCGA TCGCCCGTCG CGCATGATTT TCTACCCGCC GCCGCGCGAG GGCGCGCTGC TGCTGGCCTC GTACACGTGG TCGGACGCGG CGGCAGCGTT CGCCGGCTTG AGCCGGGAAG AGGCGTTGCG CTTGGCGCTC GACGACGTGG CGGCATTGCA CGGGCCTGTC GTGCGCCAGC TCTGGGACGG CACCGGCGTC GTCAAGCGTT GGGCGGAGGA CCAGCACAGC CAGGGTGGCT TTGTGGTACA GCCGCCGGCG CTCTGGCAAA CCGAAAAGGA TGACTGGACG GTCCCTTATG GCCGCATCTA CTTTGCCGGC GAGCACACCG CCTACCCGCA CGGCTGGGTG GAGACGGCGG TCAAGTCGGC GCTGCGCGCC GCCATCAAGA TCAACAGCCG GAAGGGGCCT GCATCGGACA CGGCCAGCCC CGAGGGGCAC GCATCTGACA TGGAGGGGCA GGGGCATGTG CATGGGGTGG CCAGCAGCCC CTCGCATGAC CTGGCAAAGG AAGAAGGCAG CCACCCTCCA GTCCAAGGCC AGTTATCTCT CCAAAACACG ACCCACACGA GGACCTCGCA Protein function: 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. Also has antibacterial properties by inhibiting growth of Gram negative and Gram positive bacteria through the production of NH4(+) and H2O2 (PubMed:23355881). [The UniProt Consortium]