OXLA_MUSSP
ID OXLA_MUSSP Reviewed; 46 AA.
AC O08615;
DT 30-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 25-MAY-2022, entry version 65.
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:0000250|UniProtKB:Q96RQ9};
DE EC=1.4.3.25 {ECO:0000250|UniProtKB:Q96RQ9};
DE AltName: Full=Interleukin-4-induced protein 1 {ECO:0000250|UniProtKB:O09046};
DE Short=IL4-induced protein 1 {ECO:0000250|UniProtKB:O09046};
DE AltName: Full=Protein Fig-1 {ECO:0000303|PubMed:9122225};
DE Flags: Fragment;
GN Name=Il4i1 {ECO:0000250|UniProtKB:O09046};
GN Synonyms=Fig1 {ECO:0000303|PubMed:9122225};
OS Mus spretus (Western Mediterranean mouse) (Algerian mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10096;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION.
RX PubMed=9122225; DOI=10.1073/pnas.94.6.2507;
RA Chu C.C., Paul W.E.;
RT "Fig1, an interleukin 4-induced mouse B cell gene isolated by cDNA
RT representational difference analysis.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2507-2512(1997).
CC -!- FUNCTION: Secreted L-amino-acid oxidase that acts as a key
CC immunoregulator. Has preference for L-aromatic amino acids: converts
CC phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp) to
CC phenylpyruvic acid (PP), hydroxyphenylpyruvic acid (HPP), and indole-3-
CC pyruvic acid (I3P), respectively. Also has weak L-arginine oxidase
CC activity. Acts as a negative regulator of anti-tumor immunity by
CC mediating Trp degradation via an indole pyruvate pathway that activates
CC the transcription factor AHR. IL4I1-mediated Trp catabolism generates
CC I3P, giving rise to indole metabolites (indole-3-acetic acid (IAA) and
CC indole-3-aldehyde (I3A)) and kynurenic acid, which act as ligands for
CC AHR, a ligand-activated transcription factor that plays important roles
CC in immunity and cancer. AHR activation by indoles following IL4I1-
CC mediated Trp degradation enhances tumor progression by promoting cancer
CC cell motility and suppressing adaptive immunity. Also has an
CC immunoregulatory function in some immune cells, probably by mediating
CC Trp degradation and promoting downstream AHR activation: inhibits T-
CC cell activation and proliferation, promotes the differentiation of
CC naive CD4(+) T-cells into FOXP3(+) regulatory T-cells (Treg) and
CC regulates the development and function of B-cells (By similarity). Also
CC regulates M2 macrophage polarization by inhibiting T-cell activation
CC (By similarity). Also has antibacterial properties by inhibiting growth
CC of Gram negative and Gram positive bacteria through the production of
CC NH4(+) and H2O2 (By similarity). {ECO:0000250|UniProtKB:O09046,
CC ECO:0000250|UniProtKB:Q96RQ9}.
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;
CC Evidence={ECO:0000250|UniProtKB:Q96RQ9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13782;
CC Evidence={ECO:0000250|UniProtKB:Q96RQ9};
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:0000250|UniProtKB:Q96RQ9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61245;
CC Evidence={ECO:0000250|UniProtKB:Q96RQ9};
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:0000250|UniProtKB:Q96RQ9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61241;
CC Evidence={ECO:0000250|UniProtKB:Q96RQ9};
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:0000250|UniProtKB:Q96RQ9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61249;
CC Evidence={ECO:0000250|UniProtKB:Q96RQ9};
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:0000250|UniProtKB:Q96RQ9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51405;
CC Evidence={ECO:0000250|UniProtKB:Q96RQ9};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:O09046};
CC -!- PATHWAY: Amino-acid degradation; L-tryptophan degradation via pyruvate
CC pathway. {ECO:0000250|UniProtKB:Q96RQ9}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q96RQ9}. Lysosome
CC {ECO:0000250|UniProtKB:O09046}. Cytoplasmic vesicle, secretory vesicle,
CC acrosome {ECO:0000250|UniProtKB:Q96RQ9}. Note=Secreted at the
CC immunological synapse. {ECO:0000250|UniProtKB:Q96RQ9}.
CC -!- INDUCTION: By interleukin-4. {ECO:0000269|PubMed:9122225}.
CC -!- SIMILARITY: Belongs to the flavin monoamine oxidase family. FIG1
CC subfamily. {ECO:0000305}.
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DR EMBL; U80211; AAB51360.1; -; Genomic_DNA.
DR AlphaFoldDB; O08615; -.
DR SMR; O08615; -.
DR MGI; MGI:109552; Il4i1.
DR UniPathway; UPA00332; -.
DR GO; GO:0001669; C:acrosomal vesicle; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0001772; C:immunological synapse; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0097225; C:sperm midpiece; ISS:UniProtKB.
DR GO; GO:0001716; F:L-amino-acid oxidase activity; ISS: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; ISS:UniProtKB.
DR GO; GO:0050868; P:negative regulation of T cell activation; ISS:UniProtKB.
DR GO; GO:0002841; P:negative regulation of T cell mediated immune response to tumor cell; ISS:UniProtKB.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; ISS:UniProtKB.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0002819; P:regulation of adaptive immune response; ISS:UniProtKB.
DR GO; GO:0045577; P:regulation of B cell differentiation; ISS:UniProtKB.
DR GO; GO:0006569; P:tryptophan catabolic process; ISS:UniProtKB.
DR GO; GO:0019440; P:tryptophan catabolic process to indole-3-acetate; ISS:UniProtKB.
DR GO; GO:0006572; P:tyrosine catabolic process; ISS:UniProtKB.
PE 2: Evidence at transcript level;
KW Adaptive immunity; Cytoplasmic vesicle; FAD; Flavoprotein; Glycoprotein;
KW Immunity; Lysosome; Oxidoreductase; Secreted.
FT CHAIN <1..>46
FT /note="L-amino-acid oxidase"
FT /id="PRO_0000099873"
FT CARBOHYD 31
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT NON_TER 1
FT NON_TER 46
SQ SEQUENCE 46 AA; 5165 MW; 483CBE1F75610164 CRC64;
AFKDLKALGC KKAMNKFNKH TLLEYLLEEG NLSRPAVQLL GDVMSE
