UniProtKB - O09046 (OXLA_MOUSE)
L-amino-acid oxidase
Il4i1
Functioni
Secreted L-amino-acid oxidase that acts as a key immunoregulator (PubMed:32818467).
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:15383589).
Also has weak L-arginine oxidase activity (By similarity).
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:21469114, PubMed:28405502, PubMed:32818467).
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 (By similarity).
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 cell, 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:25778793, PubMed:29288206).
Also regulates M2 macrophage polarization by inhibiting T-cell activation (PubMed:26599209).
Also has antibacterial properties by inhibiting growth of Gram negative and Gram positive bacteria through the production of NH4+ and H2O2 (By similarity).
By similarity7 PublicationsCatalytic activityi
- EC:1.4.3.21 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forwardBy similarity direction.
- EC:1.4.3.25By similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
Kineticsi
- KM=6.5 mM for phenylalanine (at 37 degrees Celsius)1 Publication
- Vmax=0.0099 nmol/min/mg enzyme toward phenylalanine (at 37 degrees Celsius)1 Publication
pH dependencei
: L-tryptophan degradation via pyruvate pathway Pathwayi
This protein is involved in the pathway L-tryptophan degradation via pyruvate pathway, which is part of Amino-acid degradation.By similarityView all proteins of this organism that are known to be involved in the pathway L-tryptophan degradation via pyruvate pathway and in Amino-acid degradation.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 96 | FADBy similarity | 1 | |
Binding sitei | 115 | SubstrateBy similarity | 1 | |
Binding sitei | 286 | FAD; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Binding sitei | 395 | SubstrateBy similarity | 1 | |
Binding sitei | 479 | FADBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 68 – 69 | FADBy similarity | 2 | |
Nucleotide bindingi | 88 – 89 | FADBy similarity | 2 | |
Nucleotide bindingi | 112 – 115 | FADBy similarity | 4 | |
Nucleotide bindingi | 486 – 491 | FADBy similarity | 6 |
GO - Molecular functioni
- L-amino-acid oxidase activity Source: MGI
- L-phenylalaine oxidase activity Source: RHEA
- oxidoreductase activity Source: GO_Central
- polyamine oxidase activity Source: GO_Central
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- aromatic amino acid family metabolic process Source: MGI
- cellular amino acid catabolic process Source: GO_Central
- L-phenylalanine catabolic process Source: UniProtKB
- negative regulation of T cell activation Source: UniProtKB
- negative regulation of T cell mediated immune response to tumor cell Source: UniProtKB
- negative regulation of T cell proliferation Source: UniProtKB
- positive regulation of regulatory T cell differentiation Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- regulation of adaptive immune response Source: UniProtKB
- regulation of B cell differentiation Source: UniProtKB
- tryptophan catabolic process Source: UniProtKB
- tryptophan catabolic process to indole-3-acetate Source: UniProtKB
- tyrosine catabolic process Source: UniProtKB
Keywordsi
Molecular function | Oxidoreductase |
Biological process | Adaptive immunity, Immunity |
Ligand | FAD, Flavoprotein |
Enzyme and pathway databases
BRENDAi | 1.4.3.2, 3474 |
Reactomei | R-MMU-8964208, Phenylalanine metabolism |
UniPathwayi | UPA00332 |
Names & Taxonomyi
Protein namesi | Recommended name: L-amino-acid oxidaseCurated (EC:1.4.3.21 Publication, EC:1.4.3.25By similarity)Short name: LAAOCurated Short name: LAOCurated Alternative name(s): Interleukin-4-induced protein 11 Publication Short name: IL4-induced protein 11 Publication Short name: mIL4I11 Publication Protein Fig-11 Publication Short name: mFIG11 Publication |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:109552, Il4i1 |
Subcellular locationi
Extracellular region or secreted
- extracellular region Source: UniProtKB
Lysosome
- lysosome Source: MGI
Plasma Membrane
- immunological synapse Source: UniProtKB
Other locations
- acrosomal vesicle Source: UniProtKB
- sperm midpiece Source: UniProtKB
Keywords - Cellular componenti
Cytoplasmic vesicle, Lysosome, SecretedPathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | Sequence analysisAdd BLAST | 21 | |
ChainiPRO_0000001711 | 22 – 630 | L-amino-acid oxidaseAdd BLAST | 609 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 35 ↔ 198 | By similarity | ||
Glycosylationi | 53 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 133 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 219 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
MaxQBi | O09046 |
PaxDbi | O09046 |
PRIDEi | O09046 |
ProteomicsDBi | 294142 [O09046-1] 294143 [O09046-2] |
PTM databases
GlyGeni | O09046, 3 sites |
PhosphoSitePlusi | O09046 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Interactioni
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000113726 |
Miscellaneous databases
RNActi | O09046, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 486 – 487 | Substrate bindingBy similarity | 2 | |
Regioni | 532 – 554 | DisorderedSequence analysisAdd BLAST | 23 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG0029, Eukaryota |
InParanoidi | O09046 |
OrthoDBi | 367611at2759 |
Family and domain databases
Gene3Di | 3.50.50.60, 1 hit |
InterProi | View protein in InterPro IPR002937, Amino_oxidase IPR036188, FAD/NAD-bd_sf IPR001613, Flavin_amine_oxidase |
Pfami | View protein in Pfam PF01593, Amino_oxidase, 1 hit |
PRINTSi | PR00757, AMINEOXDASEF |
SUPFAMi | SSF51905, SSF51905, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative promoter usage. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAGLALRLVL AATLLGLAGS LDWKAASSLN PIEKCMEDHD YEQLLKVVTL
60 70 80 90 100
GLNRTSKPQK VVVVGAGVAG LVAAKMLSDA GHKVTILEAD NRIGGRIFTF
110 120 130 140 150
RDEKTGWIGE LGAMRMPSSH RILHKLCRTL GLNLTQFTQY DENTWTEVHN
160 170 180 190 200
VKLRNYVVEK MPEKLGYNLN NRERGHSPED IYQMALNKAF KDLKALGCKK
210 220 230 240 250
AMNKFNKHTL LEYLLEEGNL SRPAVQLLGD VMSEEGFFYL SFAEALRAHA
260 270 280 290 300
CLSDRLRYSR IVGGWDLLPR ALLSSLSGAL LLNAPVVSIT QGRNDVRVHI
310 320 330 340 350
ATSLHSEKTL TADVVLLTAS GPALQRITFS PPLTRKRQEA LRALHYVAAS
360 370 380 390 400
KVFLSFRRPF WHEEHIEGGH SNTDRPSRLI FYPARGEGSL LLASYTWSDA
410 420 430 440 450
AAPFAGLSTD QTLRLVLQDV AALHGPVVFR LWDGRGVVKR WAEDPHSQGG
460 470 480 490 500
FVVQPPLYGR EAEDYDWSAP FGRIYFAGEH TALPHGWVET AVKSGLRAAV
510 520 530 540 550
RINNNYGYGE VDPQMMEHAY AEANYLDQYP EGERPEEQQA REEVSPDEQE
560 570 580 590 600
PSHKHLLVET SPEGQQHAFV EAIPELQGHV FVETVPQEKG HAHQNIYPSE
610 620 630
HVQVHGEVIP EWHGHGGSGT PQMHRVGDHS
The sequence of this isoform differs from the canonical sequence as follows:
1-5: MAGLA → MGARRAPQRPPCT
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD3Z4E0 | D3Z4E0_MOUSE | Amine oxidase | Il4i1 | 638 | Annotation score: | ||
A0A0R4J0C2 | A0A0R4J0C2_MOUSE | Amine oxidase | Il4i1 | 630 | Annotation score: | ||
G3UXA7 | G3UXA7_MOUSE | L-amino-acid oxidase | Il4i1 | 54 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 12 | A → V in AAO17038 (Ref. 2) Curated | 1 | |
Sequence conflicti | 12 | A → V in AAO17039 (Ref. 2) Curated | 1 | |
Sequence conflicti | 56 | S → L in AAO65453 (Ref. 2) Curated | 1 | |
Sequence conflicti | 56 | S → L in AAS00457 (Ref. 2) Curated | 1 | |
Sequence conflicti | 184 | M → V in BAE30174 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 184 | M → V in BAE31293 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 385 | R → Q in AAO23118 (Ref. 2) Curated | 1 | |
Sequence conflicti | 385 | R → Q in BAE21502 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 385 | R → Q in BAE29676 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 385 | R → Q in BAE30047 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 385 | R → Q in BAE30174 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 385 | R → Q in BAE31293 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 454 | Q → R in BAE21502 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 537 | E → Q in BAE21502 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 551 | P → L in AAO17038 (Ref. 2) Curated | 1 | |
Sequence conflicti | 551 | P → L in AAO17039 (Ref. 2) Curated | 1 | |
Sequence conflicti | 568 | A → M in AAO17038 (Ref. 2) Curated | 1 | |
Sequence conflicti | 568 | A → M in AAO17039 (Ref. 2) Curated | 1 | |
Sequence conflicti | 598 – 630 | PSEHV…VGDHS → LRSMYRCMGKSSLSGMVMGD LAPRKCTEWGTTPNRKEEVS TQLLSQPSSGQTDHLH in BAB29253 (PubMed:16141072).CuratedAdd BLAST | 33 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_017174 | 1 – 5 | MAGLA → MGARRAPQRPPCT in isoform 2. 1 Publication | 5 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U70429 mRNA Translation: AAB51353.1 U70430 Genomic RNA Translation: AAB51354.1 AF538041 Genomic DNA Translation: AAM15529.1 AY442170 Genomic DNA Translation: AAM15530.2 AY157537 Genomic DNA Translation: AAO17038.1 AY157538 mRNA Translation: AAO17039.1 AY161348 Genomic DNA Translation: AAO23118.1 AY178834 Genomic DNA Translation: AAO65453.1 AY442343 Genomic DNA Translation: AAS00457.1 AK014297 mRNA Translation: BAB29253.1 Different initiation. AK133082 mRNA Translation: BAE21502.1 AK150582 mRNA Translation: BAE29676.1 AK151030 mRNA Translation: BAE30047.1 AK151171 mRNA Translation: BAE30174.1 AK152538 mRNA Translation: BAE31293.1 AK172393 mRNA Translation: BAE42981.1 BC115960 mRNA Translation: AAI15961.1 U89428 Transcribed RNA Translation: AAC36534.1 U89429 mRNA Translation: AAC36535.1 |
CCDSi | CCDS21217.1 [O09046-1] |
RefSeqi | NP_001164495.1, NM_001171024.1 NP_034345.2, NM_010215.3 |
Genome annotation databases
GeneIDi | 100328588 14204 |
KEGGi | mmu:100328588 mmu:14204 |
Keywords - Coding sequence diversityi
Alternative promoter usageSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U70429 mRNA Translation: AAB51353.1 U70430 Genomic RNA Translation: AAB51354.1 AF538041 Genomic DNA Translation: AAM15529.1 AY442170 Genomic DNA Translation: AAM15530.2 AY157537 Genomic DNA Translation: AAO17038.1 AY157538 mRNA Translation: AAO17039.1 AY161348 Genomic DNA Translation: AAO23118.1 AY178834 Genomic DNA Translation: AAO65453.1 AY442343 Genomic DNA Translation: AAS00457.1 AK014297 mRNA Translation: BAB29253.1 Different initiation. AK133082 mRNA Translation: BAE21502.1 AK150582 mRNA Translation: BAE29676.1 AK151030 mRNA Translation: BAE30047.1 AK151171 mRNA Translation: BAE30174.1 AK152538 mRNA Translation: BAE31293.1 AK172393 mRNA Translation: BAE42981.1 BC115960 mRNA Translation: AAI15961.1 U89428 Transcribed RNA Translation: AAC36534.1 U89429 mRNA Translation: AAC36535.1 |
CCDSi | CCDS21217.1 [O09046-1] |
RefSeqi | NP_001164495.1, NM_001171024.1 NP_034345.2, NM_010215.3 |
3D structure databases
AlphaFoldDBi | O09046 |
SMRi | O09046 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000113726 |
PTM databases
GlyGeni | O09046, 3 sites |
PhosphoSitePlusi | O09046 |
Proteomic databases
MaxQBi | O09046 |
PaxDbi | O09046 |
PRIDEi | O09046 |
ProteomicsDBi | 294142 [O09046-1] 294143 [O09046-2] |
Protocols and materials databases
DNASUi | 14204 |
Genome annotation databases
GeneIDi | 100328588 14204 |
KEGGi | mmu:100328588 mmu:14204 |
Organism-specific databases
CTDi | 100328588 259307 |
MGIi | MGI:109552, Il4i1 |
Phylogenomic databases
eggNOGi | KOG0029, Eukaryota |
InParanoidi | O09046 |
OrthoDBi | 367611at2759 |
Enzyme and pathway databases
UniPathwayi | UPA00332 |
BRENDAi | 1.4.3.2, 3474 |
Reactomei | R-MMU-8964208, Phenylalanine metabolism |
Miscellaneous databases
BioGRID-ORCSi | 100328588, 2 hits in 19 CRISPR screens 14204, 3 hits in 40 CRISPR screens |
PROi | PR:O09046 |
RNActi | O09046, protein |
SOURCEi | Search... |
Family and domain databases
Gene3Di | 3.50.50.60, 1 hit |
InterProi | View protein in InterPro IPR002937, Amino_oxidase IPR036188, FAD/NAD-bd_sf IPR001613, Flavin_amine_oxidase |
Pfami | View protein in Pfam PF01593, Amino_oxidase, 1 hit |
PRINTSi | PR00757, AMINEOXDASEF |
SUPFAMi | SSF51905, SSF51905, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | OXLA_MOUSE | |
Accessioni | O09046Primary (citable) accession number: O09046 Secondary accession number(s): Q1LZI6 Q9CXK7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
Last sequence update: | July 1, 1997 | |
Last modified: | May 25, 2022 | |
This is version 162 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families