Overview
| Uniprot ID | Q96RQ9 |
|---|
| Protein Name | L-amino-acid oxidase |
|---|
| Gene Name | IL4I1 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 165 |
VVEKVPEKLGYALRP |
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 (By similarity). Also has antibacterial properties by inhibiting growth of Gram negative and Gram positive bacteria through the production of NH4(+) and H2O2 (PubMed:23355881)
Protein Sequence
10
MAPLALHLLV
20
LVPILLSLVA
30
SQDWKAERSQ
40
DPFEKCMQDP
50
DYEQLLKVVT
60
WGLNRTLKPQ
70
RVIVVGAGVA
80
GLVAAKVLSD
90
AGHKVTILEA
100
DNRIGGRIFT
110
YRDQNTGWIG
120
ELGAMRMPSS
130
HRILHKLCQG
140
LGLNLTKFTQ
150
YDKNTWTEVH
160
EVKLRNYVVE
170
KVPEKLGYAL
180
RPQEKGHSPE
190
DIYQMALNQA
200
LKDLKALGCR
210
KAMKKFERHT
220
LLEYLLGEGN
230
LSRPAVQLLG
240
DVMSEDGFFY
250
LSFAEALRAH
260
SCLSDRLQYS
270
RIVGGWDLLP
280
RALLSSLSGL
290
VLLNAPVVAM
300
TQGPHDVHVQ
310
IETSPPARNL
320
KVLKADVVLL
330
TASGPAVKRI
340
TFSPPLPRHM
350
QEALRRLHYV
360
PATKVFLSFR
370
RPFWREEHIE
380
GGHSNTDRPS
390
RMIFYPPPRE
400
GALLLASYTW
410
SDAAAAFAGL
420
SREEALRLAL
430
DDVAALHGPV
440
VRQLWDGTGV
450
VKRWAEDQHS
460
QGGFVVQPPA
470
LWQTEKDDWT
480
VPYGRIYFAG
490
EHTAYPHGWV
500
ETAVKSALRA
510
AIKINSRKGP
520
ASDTASPEGH
530
ASDMEGQGHV
540
HGVASSPSHD
550
LAKEEGSHPP
560
VQGQLSLQNT
THTRTSH
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0001669 |
acrosomal vesicle |
| Cellular Component |
GO:0005576 |
extracellular region |
| Cellular Component |
GO:0001772 |
immunological synapse |
| Cellular Component |
GO:0005764 |
lysosome |
| Cellular Component |
GO:0097225 |
sperm midpiece |
| Molecular Function |
GO:0001716 |
L-amino-acid oxidase activity |
| Molecular Function |
GO:0106329 |
L-phenylalaine oxidase activity |
| Biological Process |
GO:0002250 |
adaptive immune response |
| Biological Process |
GO:0009063 |
amino acid catabolic process |
| Biological Process |
GO:0006559 |
L-phenylalanine catabolic process |
| Biological Process |
GO:0006569 |
L-tryptophan catabolic process |
| Biological Process |
GO:0019440 |
L-tryptophan catabolic process to indole-3-acetate |
| Biological Process |
GO:0006572 |
L-tyrosine catabolic process |
| Biological Process |
GO:0050868 |
negative regulation of T cell activation |
| Biological Process |
GO:0002841 |
negative regulation of T cell mediated immune response to tumor cell |
| Biological Process |
GO:0042130 |
negative regulation of T cell proliferation |
| Biological Process |
GO:0045591 |
positive regulation of regulatory T cell differentiation |
| Biological Process |
GO:0045944 |
positive regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0002819 |
regulation of adaptive immune response |
| Biological Process |
GO:0045577 |
regulation of B cell differentiation |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.