ID OXLA_HUMAN Reviewed; 567 AA. AC Q96RQ9; Q1WMJ3; Q4GZN1; Q4GZN2; Q6P2Q3; Q8TEM5; Q96RQ8; DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-MAR-2024, entry version 177. DE RecName: Full=L-amino-acid oxidase {ECO:0000305}; DE Short=LAAO {ECO:0000305}; DE Short=LAO {ECO:0000305}; DE EC=1.4.3.2 {ECO:0000269|PubMed:17356132, ECO:0000269|PubMed:25767141, ECO:0000269|PubMed:26673964, ECO:0000269|PubMed:31812258, ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000}; DE EC=1.4.3.25 {ECO:0000269|PubMed:26673964}; DE AltName: Full=Interleukin-4-induced protein 1 {ECO:0000303|PubMed:16029492}; DE Short=IL4-induced protein 1 {ECO:0000303|PubMed:16029492}; DE Short=hIL4I1 {ECO:0000303|PubMed:17356132}; DE AltName: Full=Protein Fig-1 {ECO:0000303|PubMed:12031486}; DE Short=hFIG1 {ECO:0000303|PubMed:12031486}; DE Flags: Precursor; GN Name=IL4I1 {ECO:0000303|PubMed:16029492}; GN Synonyms=FIG1 {ECO:0000303|PubMed:12031486}; GN ORFNames=UNQ636/PRO1265 {ECO:0000303|PubMed:12975309}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY, RP AND INDUCTION. RX PubMed=12031486; DOI=10.1016/s0167-4781(02)00295-6; RA Chavan S.S., Tian W., Hsueh K., Jawaheer D., Gregersen P.K., Chu C.C.; RT "Characterization of the human homolog of the IL-4 induced gene-1 (Fig1)."; RL Biochim. Biophys. Acta 1576:70-80(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE PROMOTER USAGE, AND RP SUBCELLULAR LOCATION. RX PubMed=16029492; DOI=10.1186/1741-7007-3-16; RA Wiemann S., Kolb-Kokocinski A., Poustka A.; RT "Alternative pre-mRNA processing regulates cell-type specific expression of RT the IL4l1 and NUP62 genes."; RL BMC Biol. 3:16-16(2005). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Testis; RA Chu C.C., Reese S.T., George J., Tian W., Yuan L., Millan C., Marmar J.L., RA Benoff S.; RT "Interleukin-4 induced gene-1 variant (IL4I1_v2) is expressed during RT spermatogenesis and is decreased in pathologies with hypospermatogenesis."; RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Spleen; RA Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O.; RT "The nucleotide sequence of a long cDNA clone isolated from human spleen."; RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Ovary, and PNS; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE OF 22-36. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [9] RP TISSUE SPECIFICITY. RX PubMed=12446450; DOI=10.1182/blood-2002-07-2215; RA Copie-Bergman C., Boulland M.L., Dehoulle C., Moeller P., Farcet J.P., RA Dyer M.J., Haioun C., Romeo P.H., Gaulard P., Leroy K.; RT "Interleukin 4-induced gene 1 is activated in primary mediastinal large B- RT cell lymphoma."; RL Blood 101:2756-2761(2003). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR RP LOCATION, GLYCOSYLATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF GLU-481. RX PubMed=17356132; DOI=10.1182/blood-2006-07-036210; RA Boulland M.L., Marquet J., Molinier-Frenkel V., Moeller P., Guiter C., RA Lasoudris F., Copie-Bergman C., Baia M., Gaulard P., Leroy K., RA Castellano F.; RT "Human IL4I1 is a secreted L-phenylalanine oxidase expressed by mature RT dendritic cells that inhibits T-lymphocyte proliferation."; RL Blood 110:220-227(2007). RN [11] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-220. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [12] RP TISSUE SPECIFICITY. RX PubMed=19436310; DOI=10.1038/leu.2008.380; RA Carbonnelle-Puscian A., Copie-Bergman C., Baia M., Martin-Garcia N., RA Allory Y., Haioun C., Cremades A., Abd-Alsamad I., Farcet J.P., Gaulard P., RA Castellano F., Molinier-Frenkel V.; RT "The novel immunosuppressive enzyme IL4I1 is expressed by neoplastic cells RT of several B-cell lymphomas and by tumor-associated macrophages."; RL Leukemia 23:952-960(2009). RN [13] RP FUNCTION. RX PubMed=23355881; DOI=10.1371/journal.pone.0054589; RA Puiffe M.L., Lachaise I., Molinier-Frenkel V., Castellano F.; RT "Antibacterial properties of the mammalian L-amino acid oxidase IL4I1."; RL PLoS ONE 8:e54589-e54589(2013). RN [14] RP FUNCTION. RX PubMed=25446972; DOI=10.1002/eji.201444897; RA Scarlata C.M., Celse C., Pignon P., Ayyoub M., Valmori D.; RT "Differential expression of the immunosuppressive enzyme IL4I1 in human RT induced Aiolos+, but not natural Helios+, FOXP3+ Treg cells."; RL Eur. J. Immunol. 45:474-479(2015). RN [15] RP FUNCTION. RX PubMed=25778793; DOI=10.1002/eji.201445000; RA Cousin C., Aubatin A., Le Gouvello S., Apetoh L., Castellano F., RA Molinier-Frenkel V.; RT "The immunosuppressive enzyme IL4I1 promotes FoxP3(+) regulatory T RT lymphocyte differentiation."; RL Eur. J. Immunol. 45:1772-1782(2015). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [17] RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=25767141; DOI=10.1530/rep-14-0621; RA Houston B., Curry B., Aitken R.J.; RT "Human spermatozoa possess an IL4I1 L-amino acid oxidase with a potential RT role in sperm function."; RL Reproduction 149:587-596(2015). RN [18] RP FUNCTION, CATALYTIC ACTIVITY, VARIANTS ASP-92 AND GLY-102, AND RP CHARACTERIZATION OF VARIANTS ASP-92 AND GLY-102. RX PubMed=26673964; DOI=10.1038/gene.2015.55; RA Molinier-Frenkel V., Mestivier D., Castellano F.; RT "Alterations of the immunosuppressive IL4I1 enzyme activity induced by RT naturally occurring SNP/mutations."; RL Genes Immun. 17:148-152(2016). RN [19] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=28891065; DOI=10.1002/eji.201646769; RA Aubatin A., Sako N., Decrouy X., Donnadieu E., Molinier-Frenkel V., RA Castellano F.; RT "IL4-induced gene 1 is secreted at the immune synapse and modulates TCR RT activation independently of its enzymatic activity."; RL Eur. J. Immunol. 48:106-119(2018). RN [20] RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=31812258; DOI=10.1016/j.bioorg.2019.103463; RA Presset M., Djordjevic D., Dupont A., Le Gall E., Molinier-Frenkel V., RA Castellano F.; RT "Identification of inhibitors of the immunosuppressive enzyme IL4I1."; RL Bioorg. Chem. 94:103463-103463(2020). RN [21] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=32818467; DOI=10.1016/j.cell.2020.07.038; RA Sadik A., Somarribas Patterson L.F., Oeztuerk S., Mohapatra S.R., RA Panitz V., Secker P.F., Pfaender P., Loth S., Salem H., Prentzell M.T., RA Berdel B., Iskar M., Faessler E., Reuter F., Kirst I., Kalter V., RA Foerster K.I., Jaeger E., Guevara C.R., Sobeh M., Hielscher T., Poschet G., RA Reinhardt A., Hassel J.C., Zapatka M., Hahn U., von Deimling A., Hopf C., RA Schlichting R., Escher B.I., Burhenne J., Haefeli W.E., Ishaque N., RA Boehme A., Schaeuble S., Thedieck K., Trump S., Seiffert M., Opitz C.A.; RT "IL4I1 is a metabolic immune checkpoint that activates the AHR and promotes RT tumor progression."; RL Cell 182:1252-1270(2020). RN [22] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=32866000; DOI=10.1021/acs.jafc.0c03735; RA Zhang X., Gan M., Li J., Li H., Su M., Tan D., Wang S., Jia M., Zhang L., RA Chen G.; RT "An endogenous indole pyruvate pathway for tryptophan metabolism mediated RT by IL4I1."; RL J. Agric. Food Chem. 68:10678-10684(2020). CC -!- FUNCTION: Secreted L-amino-acid oxidase that acts as a key CC immunoregulator (PubMed:17356132, PubMed:32818467, PubMed:32866000). CC Has preference for L-aromatic amino acids: converts phenylalanine CC (Phe), tyrosine (Tyr) and tryptophan (Trp) to phenylpyruvic acid (PP), CC hydroxyphenylpyruvic acid (HPP), and indole-3-pyruvic acid (I3P), CC respectively (PubMed:17356132, PubMed:32818467, PubMed:32866000). Also CC has weak L-arginine oxidase activity (PubMed:26673964). Acts as a CC negative regulator of anti-tumor immunity by mediating Trp degradation CC via an indole pyruvate pathway that activates the transcription factor CC AHR (PubMed:32818467, PubMed:32866000). IL4I1-mediated Trp catabolism CC generates I3P, giving rise to indole metabolites (indole-3-acetic acid CC (IAA) and indole-3-aldehyde (I3A)) and kynurenic acid, which act as CC ligands for AHR, a ligand-activated transcription factor that plays CC important roles in immunity and cancer (PubMed:32818467, CC PubMed:32866000). AHR activation by indoles following IL4I1-mediated CC Trp degradation enhances tumor progression by promoting cancer cell CC motility and suppressing adaptive immunity (PubMed:32818467). Also has CC an immunoregulatory function in some immune cells, probably by CC mediating Trp degradation and promoting downstream AHR activation: CC inhibits T-cell activation and proliferation, promotes the CC differentiation of naive CD4(+) T-cells into FOXP3(+) regulatory T- CC cells (Treg) and regulates the development and function of B-cells CC (PubMed:17356132, PubMed:25446972, PubMed:25778793, PubMed:28891065). CC Also regulates M2 macrophage polarization by inhibiting T-cell CC activation (By similarity). Also has antibacterial properties by CC inhibiting growth of Gram negative and Gram positive bacteria through CC the production of NH4(+) and H2O2 (PubMed:23355881). CC {ECO:0000250|UniProtKB:O09046, ECO:0000269|PubMed:17356132, CC ECO:0000269|PubMed:23355881, ECO:0000269|PubMed:25446972, CC ECO:0000269|PubMed:25778793, ECO:0000269|PubMed:26673964, CC ECO:0000269|PubMed:28891065, ECO:0000269|PubMed:32818467, CC ECO:0000269|PubMed:32866000}. CC -!- CATALYTIC ACTIVITY: CC Reaction=an L-alpha-amino acid + H2O + O2 = a 2-oxocarboxylate + H2O2 + CC NH4(+); Xref=Rhea:RHEA:13781, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:35179, CC ChEBI:CHEBI:59869; EC=1.4.3.2; Evidence={ECO:0000269|PubMed:17356132, CC ECO:0000269|PubMed:25767141, ECO:0000269|PubMed:26673964, CC ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13782; CC Evidence={ECO:0000269|PubMed:17356132, ECO:0000269|PubMed:25767141, CC ECO:0000269|PubMed:26673964, ECO:0000269|PubMed:32818467, CC ECO:0000269|PubMed:32866000}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + L-tryptophan + O2 = H2O2 + indole-3-pyruvate + NH4(+); CC Xref=Rhea:RHEA:61244, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:17640, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:57912; Evidence={ECO:0000269|PubMed:17356132, CC ECO:0000269|PubMed:25767141, ECO:0000269|PubMed:32818467, CC ECO:0000269|PubMed:32866000}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61245; CC Evidence={ECO:0000269|PubMed:17356132, ECO:0000269|PubMed:25767141, CC ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + L-phenylalanine + O2 = 3-phenylpyruvate + H2O2 + NH4(+); CC Xref=Rhea:RHEA:61240, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:18005, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:58095; Evidence={ECO:0000269|PubMed:17356132, CC ECO:0000269|PubMed:25767141, ECO:0000269|PubMed:26673964, CC ECO:0000269|PubMed:31812258, ECO:0000269|PubMed:32818467}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61241; CC Evidence={ECO:0000269|PubMed:17356132, ECO:0000269|PubMed:25767141, CC ECO:0000269|PubMed:26673964, ECO:0000269|PubMed:31812258, CC ECO:0000269|PubMed:32818467}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + L-tyrosine + O2 = 3-(4-hydroxyphenyl)pyruvate + H2O2 + CC NH4(+); Xref=Rhea:RHEA:61248, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:36242, CC ChEBI:CHEBI:58315; Evidence={ECO:0000269|PubMed:17356132, CC ECO:0000269|PubMed:32818467}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61249; CC Evidence={ECO:0000269|PubMed:17356132, ECO:0000269|PubMed:32818467}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + L-arginine + O2 = 5-guanidino-2-oxopentanoate + H2O2 + CC NH4(+); Xref=Rhea:RHEA:51404, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:32682, CC ChEBI:CHEBI:58489; EC=1.4.3.25; CC Evidence={ECO:0000269|PubMed:26673964}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51405; CC Evidence={ECO:0000269|PubMed:26673964}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000250|UniProtKB:O09046}; CC -!- ACTIVITY REGULATION: L-amino-acid oxidase activity toward phenylalanine CC (Phe) is specfically inhibited by a number of Phe derivatives, such as CC Cp3 (ethyl 3-(2,6-dichlorophenyl)-2-(piperidin-1-yl)propanoate) or Cp2- CC SO4 (PubMed:31812258). Cp3 is a very potent inhibitor for activity CC toward phenylalanine but is toxic (PubMed:31812258). In contrast, Cp2- CC SO4 is less efficient but not toxic and is able to reverse CC immunosuppressive action of IL4I1 in vitro (PubMed:31812258). CC {ECO:0000269|PubMed:31812258}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.48 mM for L-phenylalanine {ECO:0000269|PubMed:17356132}; CC -!- PATHWAY: Amino-acid degradation; L-tryptophan degradation via pyruvate CC pathway. {ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000}. CC -!- INTERACTION: CC Q96RQ9; Q96CV9: OPTN; NbExp=3; IntAct=EBI-20831744, EBI-748974; CC Q96RQ9; O76024: WFS1; NbExp=3; IntAct=EBI-20831744, EBI-720609; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17356132, CC ECO:0000269|PubMed:28891065, ECO:0000269|PubMed:32818467}. Lysosome CC {ECO:0000250|UniProtKB:O09046}. Cytoplasmic vesicle, secretory vesicle, CC acrosome {ECO:0000269|PubMed:25767141}. Note=Secreted at the CC immunological synapse. {ECO:0000269|PubMed:28891065}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96RQ9-1; Sequence=Displayed; CC Name=2; Synonyms=IL4I1_2 {ECO:0000303|PubMed:16029492}; CC IsoId=Q96RQ9-2; Sequence=VSP_017173; CC -!- TISSUE SPECIFICITY: Primarily found in immune tissues, with the highest CC expression in lymph nodes and spleen (PubMed:12031486, CC PubMed:12446450). Present in germinal center macrophages and CC inflammatory myeloid cells and antigen-presenting cells (at protein CC level) (PubMed:17356132). Also present in spermatozoa (at protein CC level) (PubMed:25767141). Highly expressed in primary mediastinal large CC B-cell lymphoma, a specific subtype of diffuse large B-cell lymphoma CC (PubMed:12446450). Expressed by neoplastic cells of several B-cell CC lymphomas and by tumor-associated macrophages (PubMed:19436310). CC {ECO:0000269|PubMed:12031486, ECO:0000269|PubMed:12446450, CC ECO:0000269|PubMed:17356132, ECO:0000269|PubMed:19436310, CC ECO:0000269|PubMed:25767141}. CC -!- INDUCTION: By IL4/interleukin-4 (PubMed:12031486). Expression is up- CC regulated in numerous cancer and metastasis: expression is induced by CC immune checkpoint blockade (PubMed:32818467). CC {ECO:0000269|PubMed:12031486, ECO:0000269|PubMed:32818467}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:17356132}. CC -!- MISCELLANEOUS: [Isoform 2]: Uses the promoter of the upstream NUP62 CC gene and shares the first 2 non-coding exons with NUP62. CC {ECO:0000305|PubMed:16029492}. CC -!- SIMILARITY: Belongs to the flavin monoamine oxidase family. FIG1 CC subfamily. {ECO:0000305}. CC -!- CAUTION: According to a report, acts as a negative regulator of T-cell CC activation independently of its enzymatic activity (PubMed:28891065). CC However, authors of this study only tested enzyme activity via CC phenylalanine (Phe) deprivation and not via tryptophan (Trp). As IL4I1 CC immunoregulator activity is mediated via Trp degradation and subsequent CC activation of the transcription factor AHR, additional experiments are CC required to confirm this statement (PubMed:32818467, PubMed:32866000). CC {ECO:0000269|PubMed:28891065, ECO:0000269|PubMed:32818467, CC ECO:0000269|PubMed:32866000, ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB84923.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAI54291.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAI54292.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAI54293.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF293462; AAK73362.1; -; mRNA. DR EMBL; AF293463; AAK73363.1; -; Genomic_DNA. DR EMBL; AJ880386; CAI54291.1; ALT_INIT; mRNA. DR EMBL; AJ880387; CAI54292.1; ALT_INIT; mRNA. DR EMBL; AJ880388; CAI54293.1; ALT_INIT; mRNA. DR EMBL; DQ079587; AAZ32711.1; -; mRNA. DR EMBL; DQ079588; AAZ32712.1; -; mRNA. DR EMBL; DQ079589; AAZ32713.1; -; mRNA. DR EMBL; AK074097; BAB84923.1; ALT_INIT; mRNA. DR EMBL; AY358933; AAQ89292.1; -; mRNA. DR EMBL; CH471177; EAW52575.1; -; Genomic_DNA. DR EMBL; BC064378; AAH64378.2; -; mRNA. DR EMBL; BC090852; AAH90852.2; -; mRNA. DR CCDS; CCDS12786.1; -. [Q96RQ9-2] DR CCDS; CCDS12787.1; -. [Q96RQ9-1] DR RefSeq; NP_001244946.1; NM_001258017.1. [Q96RQ9-2] DR RefSeq; NP_001244947.1; NM_001258018.1. [Q96RQ9-2] DR RefSeq; NP_690863.1; NM_152899.1. [Q96RQ9-1] DR RefSeq; NP_758962.1; NM_172374.2. [Q96RQ9-2] DR AlphaFoldDB; Q96RQ9; -. DR SMR; Q96RQ9; -. DR BioGRID; 129252; 13. DR IntAct; Q96RQ9; 4. DR STRING; 9606.ENSP00000472474; -. DR DrugBank; DB04166; Anthranilic acid. DR DrugBank; DB04272; Citric acid. DR DrugBank; DB03147; Flavin adenine dinucleotide. DR DrugBank; DB03214; Vinylglycine. DR GlyConnect; 1446; 2 N-Linked glycans (2 sites). DR GlyCosmos; Q96RQ9; 4 sites, 2 glycans. DR GlyGen; Q96RQ9; 5 sites, 2 N-linked glycans (2 sites). DR iPTMnet; Q96RQ9; -. DR PhosphoSitePlus; Q96RQ9; -. DR BioMuta; IL4I1; -. DR DMDM; 20138284; -. DR jPOST; Q96RQ9; -. DR MassIVE; Q96RQ9; -. DR MaxQB; Q96RQ9; -. DR PaxDb; 9606-ENSP00000472474; -. DR PeptideAtlas; Q96RQ9; -. DR ProteomicsDB; 78004; -. [Q96RQ9-1] DR ProteomicsDB; 78005; -. [Q96RQ9-2] DR Antibodypedia; 32207; 168 antibodies from 25 providers. DR DNASU; 259307; -. DR Ensembl; ENST00000341114.7; ENSP00000342557.2; ENSG00000104951.16. [Q96RQ9-2] DR Ensembl; ENST00000391826.7; ENSP00000375702.1; ENSG00000104951.16. [Q96RQ9-1] DR Ensembl; ENST00000595948.5; ENSP00000472474.1; ENSG00000104951.16. [Q96RQ9-2] DR GeneID; 259307; -. DR KEGG; hsa:259307; -. DR MANE-Select; ENST00000391826.7; ENSP00000375702.1; NM_152899.2; NP_690863.1. DR UCSC; uc002pqt.2; human. [Q96RQ9-1] DR AGR; HGNC:19094; -. DR CTD; 259307; -. DR DisGeNET; 259307; -. DR GeneCards; IL4I1; -. DR HGNC; HGNC:19094; IL4I1. DR HPA; ENSG00000104951; Group enriched (lymphoid tissue, testis). DR MalaCards; IL4I1; -. DR MIM; 609742; gene. DR neXtProt; NX_Q96RQ9; -. DR OpenTargets; ENSG00000104951; -. DR PharmGKB; PA38795; -. DR VEuPathDB; HostDB:ENSG00000104951; -. DR eggNOG; KOG0029; Eukaryota. DR GeneTree; ENSGT00940000162082; -. DR HOGENOM; CLU_004498_8_3_1; -. DR InParanoid; Q96RQ9; -. DR OMA; GIAVGWH; -. DR OrthoDB; 3597164at2759; -. DR PhylomeDB; Q96RQ9; -. DR TreeFam; TF313314; -. DR PathwayCommons; Q96RQ9; -. DR Reactome; R-HSA-8964208; Phenylalanine metabolism. DR SignaLink; Q96RQ9; -. DR UniPathway; UPA00332; -. DR BioGRID-ORCS; 259307; 18 hits in 1156 CRISPR screens. DR ChiTaRS; IL4I1; human. DR GenomeRNAi; 259307; -. DR Pharos; Q96RQ9; Tbio. DR PRO; PR:Q96RQ9; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q96RQ9; Protein. DR Bgee; ENSG00000104951; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 106 other cell types or tissues. DR ExpressionAtlas; Q96RQ9; baseline and differential. DR GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell. DR GO; GO:0097225; C:sperm midpiece; IDA:UniProtKB. DR GO; GO:0001716; F:L-amino-acid oxidase activity; IDA:UniProtKB. DR GO; GO:0106329; F:L-phenylalaine oxidase activity; IEA:RHEA. DR GO; GO:0046592; F:polyamine oxidase activity; IBA:GO_Central. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0009063; P:amino acid catabolic process; IBA:GO_Central. DR GO; GO:0006559; P:L-phenylalanine catabolic process; IDA:UniProtKB. DR GO; GO:0050868; P:negative regulation of T cell activation; IDA:UniProtKB. DR GO; GO:0002841; P:negative regulation of T cell mediated immune response to tumor cell; IDA:UniProtKB. DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:UniProtKB. DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0002819; P:regulation of adaptive immune response; IDA:UniProtKB. DR GO; GO:0045577; P:regulation of B cell differentiation; ISS:UniProtKB. DR GO; GO:0006569; P:tryptophan catabolic process; IDA:UniProtKB. DR GO; GO:0019440; P:tryptophan catabolic process to indole-3-acetate; IDA:UniProtKB. DR GO; GO:0006572; P:tyrosine catabolic process; IDA:UniProtKB. DR Gene3D; 3.90.660.10; -; 2. DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 1. DR Gene3D; 1.10.405.10; Guanine Nucleotide Dissociation Inhibitor, domain 1; 1. DR InterPro; IPR002937; Amino_oxidase. DR InterPro; IPR036188; FAD/NAD-bd_sf. DR InterPro; IPR001613; Flavin_amine_oxidase. DR PANTHER; PTHR10742; FLAVIN MONOAMINE OXIDASE; 1. DR PANTHER; PTHR10742:SF21; L-AMINO-ACID OXIDASE; 1. DR Pfam; PF01593; Amino_oxidase; 1. DR PRINTS; PR00757; AMINEOXDASEF. DR SUPFAM; SSF54373; FAD-linked reductases, C-terminal domain; 1. DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1. DR Genevisible; Q96RQ9; HS. PE 1: Evidence at protein level; KW Adaptive immunity; Alternative promoter usage; Alternative splicing; KW Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond; FAD; KW Flavoprotein; Glycoprotein; Immunity; Lysosome; Oxidoreductase; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..21 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 22..567 FT /note="L-amino-acid oxidase" FT /id="PRO_0000001710" FT REGION 506..567 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 551..567 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 69..70 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P81382" FT BINDING 89..90 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P81382" FT BINDING 97 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P81382" FT BINDING 113..116 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P81382" FT BINDING 116 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P81382" FT BINDING 287 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P81382" FT BINDING 398 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P81382" FT BINDING 481 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000305|PubMed:17356132" FT BINDING 488..493 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P81382" FT BINDING 488..489 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P81382" FT CARBOHYD 54 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 134 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 220 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 559 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 36..199 FT /evidence="ECO:0000250|UniProtKB:P81382" FT VAR_SEQ 1..5 FT /note="MAPLA -> MPNDDFCPGLTIKAMGAERAPQRQPCT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16029492, ECO:0000303|Ref.3" FT /id="VSP_017173" FT VARIANT 92 FT /note="N -> D (increased L-amino-acid oxidase activity; FT dbSNP:rs111772144)" FT /evidence="ECO:0000269|PubMed:26673964" FT /id="VAR_083941" FT VARIANT 102 FT /note="R -> G (in an ovarian cancer; decreased L-amino-acid FT oxidase activity)" FT /evidence="ECO:0000269|PubMed:26673964" FT /id="VAR_083942" FT VARIANT 501 FT /note="A -> S (in dbSNP:rs2290772)" FT /id="VAR_048260" FT MUTAGEN 481 FT /note="E->A: Abolished L-amino-acid oxidase activity." FT /evidence="ECO:0000269|PubMed:17356132" FT CONFLICT 24 FT /note="W -> R (in Ref. 7; AAH64378)" FT /evidence="ECO:0000305" FT CONFLICT 114 FT /note="A -> T (in Ref. 2; CAI54291/CAI54293)" FT /evidence="ECO:0000305" SQ SEQUENCE 567 AA; 62881 MW; FFF953CB28D22F19 CRC64; MAPLALHLLV LVPILLSLVA SQDWKAERSQ DPFEKCMQDP DYEQLLKVVT WGLNRTLKPQ RVIVVGAGVA GLVAAKVLSD AGHKVTILEA DNRIGGRIFT YRDQNTGWIG ELGAMRMPSS HRILHKLCQG LGLNLTKFTQ YDKNTWTEVH EVKLRNYVVE KVPEKLGYAL RPQEKGHSPE DIYQMALNQA LKDLKALGCR KAMKKFERHT LLEYLLGEGN LSRPAVQLLG DVMSEDGFFY LSFAEALRAH SCLSDRLQYS RIVGGWDLLP RALLSSLSGL VLLNAPVVAM TQGPHDVHVQ IETSPPARNL KVLKADVVLL TASGPAVKRI TFSPPLPRHM QEALRRLHYV PATKVFLSFR RPFWREEHIE GGHSNTDRPS RMIFYPPPRE GALLLASYTW SDAAAAFAGL SREEALRLAL DDVAALHGPV VRQLWDGTGV VKRWAEDQHS QGGFVVQPPA LWQTEKDDWT VPYGRIYFAG EHTAYPHGWV ETAVKSALRA AIKINSRKGP ASDTASPEGH ASDMEGQGHV HGVASSPSHD LAKEEGSHPP VQGQLSLQNT THTRTSH //