OXLA_HUMAN
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 03-AUG-2022, entry version 168.
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};
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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 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; Q96RQ9; -.
DR PeptideAtlas; Q96RQ9; -.
DR PRIDE; Q96RQ9; -.
DR ProteomicsDB; 78004; -. [Q96RQ9-1]
DR ProteomicsDB; 78005; -. [Q96RQ9-2]
DR Antibodypedia; 32207; 154 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 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; YTHAWIA; -.
DR OrthoDB; 367611at2759; -.
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; 17 hits in 1075 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 left testis and 105 other tissues.
DR ExpressionAtlas; Q96RQ9; baseline and differential.
DR Genevisible; Q96RQ9; HS.
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:0016491; F:oxidoreductase activity; IBA:GO_Central.
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:cellular 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; 3.50.50.60; -; 1.
DR InterPro; IPR002937; Amino_oxidase.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR001613; Flavin_amine_oxidase.
DR Pfam; PF01593; Amino_oxidase; 1.
DR PRINTS; PR00757; AMINEOXDASEF.
DR SUPFAM; SSF51905; SSF51905; 1.
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
