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    IL4I1 interleukin 4 induced 1 [ Homo sapiens (human) ]

    Gene ID: 259307, updated on 27-Nov-2024

    Summary

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    Official Symbol
    IL4I1provided by HGNC
    Official Full Name
    interleukin 4 induced 1provided by HGNC
    Primary source
    HGNC:HGNC:19094
    See related
    Ensembl:ENSG00000104951 MIM:609742; AllianceGenome:HGNC:19094
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    LAO; FIG1; LAAO; hIL4I1
    Summary
    This gene encodes a secreted L-amino acid oxidase protein which primarily catabolizes L-phenylalanine and, to a lesser extent, L-arginine. The expression of this gene is induced by the cytokine interleukin 4 in B cells. This gene is also expressed in macrophages and dendritic cells. This protein may play a role immune system escape as it is expressed in tumor-associated macrophages and suppresses T-cell responses. This protein also contains domains thought to be involved in the binding of flavin adenine dinucleotide (FAD) cofactor. Multiple transcript variants encoding different isoforms have been found for this gene. Some transcripts of this gene share a promoter and exons of the 5' UTR with the overlapping NUP62 gene. [provided by RefSeq, Jul 2020]
    Expression
    Broad expression in testis (RPKM 12.4), liver (RPKM 8.9) and 22 other tissues See more
    Orthologs
    all
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    Genomic context

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    See IL4I1 in Genome Data Viewer
    Location:
    19q13.33
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (49889654..49929504, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (52889790..52929639, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (50392911..50432761, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:50373269-50373916 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:50379233-50380192 Neighboring gene AKT1 substrate 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14965 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:50381153-50382112 Neighboring gene uncharacterized LOC124904743 Neighboring gene TBC1 domain family member 17 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:50393336-50394003 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:50394004-50394672 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:50394673-50395339 Neighboring gene microRNA 4750 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14966 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14967 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14968 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:50411173-50411894 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10946 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14969 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:50415677-50416528 Neighboring gene nucleoporin 62 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:50424983-50425650 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:50425735-50426488 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10947 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10948 Neighboring gene activating transcription factor 5 Neighboring gene microRNA 4751 Neighboring gene small nucleolar RNA U3 Neighboring gene sialic acid binding Ig like lectin 11

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Origin and diversification of the L-amino oxidase family in innate immune defenses of animals. Hughes AL. Immunogenetics, 2010 Dec. PMID 20878154, Free PMC Article
    2. Emerging Role of IL-4-Induced Gene 1 as a Prognostic Biomarker Affecting the Local T-Cell Response in Human Cutaneous Melanoma. Ramspott JP, et al. J Invest Dermatol, 2018 Dec. PMID 30048651
    3. An Overview of l-Amino Acid Oxidase Functions from Bacteria to Mammals: Focus on the Immunoregulatory Phenylalanine Oxidase IL4I1. Castellano F, et al. Molecules, 2017 Dec 5. PMID 29206151, Free PMC Article
    4. IL4-induced gene 1 is secreted at the immune synapse and modulates TCR activation independently of its enzymatic activity. Aubatin A, et al. Eur J Immunol, 2018 Jan. PMID 28891065
    5. Alterations of the immunosuppressive IL4I1 enzyme activity induced by naturally occurring SNP/mutations. Molinier-Frenkel V, et al. Genes Immun, 2016 Mar. PMID 26673964

    See all (42) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. IL4I1 in M2-like macrophage promotes glioma progression and is a promising target for immunotherapy.
      Title: IL4I1 in M2-like macrophage promotes glioma progression and is a promising target for immunotherapy.
    2. Knockdown of IL4I1 Improved High Glucose-evoked Insulin Resistance in HepG2 Cells by Alleviating Inflammation and Lipotoxicity Through AHR Activation.
      Title: Knockdown of IL4I1 Improved High Glucose-evoked Insulin Resistance in HepG2 Cells by Alleviating Inflammation and Lipotoxicity Through AHR Activation.
    3. IL4i1 and IDO1: Oxidases that control a tryptophan metabolic nexus in cancer.
      Title: IL4i1 and IDO1: Oxidases that control a tryptophan metabolic nexus in cancer.
    4. Human Chorionic Gonadotropin-Stimulated Interleukin-4-Induced-1 (IL4I1) Promotes Human Decidualization via Aryl Hydrocarbon Receptor.
      Title: Human Chorionic Gonadotropin-Stimulated Interleukin-4-Induced-1 (IL4I1) Promotes Human Decidualization via Aryl Hydrocarbon Receptor.
    5. IL4I1 enhances PD-L1 expression through JAK/STAT signaling pathway in lung adenocarcinoma.
      Title: IL4I1 enhances PD-L1 expression through JAK/STAT signaling pathway in lung adenocarcinoma.
    6. IL4I1 binds to TMPRSS13 and competes with SARS-CoV-2 spike.
      Title: IL4I1 binds to TMPRSS13 and competes with SARS-CoV-2 spike.
    7. Pan-cancer analysis combined with experimental validation revealed IL4I1 as an immunological and prognostic biomarker.
      Title: Pan-cancer analysis combined with experimental validation revealed IL4I1 as an immunological and prognostic biomarker.
    8. IL4I1-driven AHR signature: a new avenue for cancer therapy.
      Title: IL4I1-driven AHR signature: a new avenue for cancer therapy.
    9. Single-cell analysis revealed that IL4I1 promoted ovarian cancer progression.
      Title: Single-cell analysis revealed that IL4I1 promoted ovarian cancer progression.
    10. Integrated analysis reveals the participation of IL4I1, ITGB7, and FUT7 in reshaping the TNBC immune microenvironment by targeting glycolysis.
      Title: Integrated analysis reveals the participation of IL4I1, ITGB7, and FUT7 in reshaping the TNBC immune microenvironment by targeting glycolysis.
    Submit: New GeneRIF Correction See all GeneRIFs (25)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables L-amino-acid oxidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables L-amino-acid oxidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables L-phenylalaine oxidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in L-phenylalanine catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in amino acid catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of T cell activation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of T cell mediated immune response to tumor cell IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of T cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of regulatory T cell differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of B cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of adaptive immune response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tryptophan catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tryptophan catabolic process to indole-3-acetate IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tyrosine catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in acrosomal vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular region IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in immunological synapse IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lysosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in sperm midpiece IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    L-amino-acid oxidase
    Names
    Fig-1 protein
    IL4-induced protein 1
    interleukin four induced 1
    NP_001244946.1
    NP_001244947.1
    NP_001372568.1
    NP_690863.1
    NP_758962.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_021170.1 RefSeqGene

      Range
      37619..44852
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001258017.2 → NP_001244946.1  L-amino-acid oxidase isoform 2 precursor

      See identical proteins and their annotated locations for NP_001244946.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 2. The first two exons of its 5' UTR are shared with an upstream gene. Variants 2, 3 and 4 encode the same protein (isoform 2).
      Source sequence(s)
      AC118342, DQ079589
      Consensus CDS
      CCDS12786.1
      UniProtKB/TrEMBL
      A2RRH1
      Conserved Domains (2) summary
      pfam01593
      Location:91 → 523
      Amino_oxidase; Flavin containing amine oxidoreductase
      pfam13450
      Location:86 → 143
      NAD_binding_8; NAD(P)-binding Rossmann-like domain

    2. NM_001258018.2 → NP_001244947.1  L-amino-acid oxidase isoform 2 precursor

      See identical proteins and their annotated locations for NP_001244947.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 2. The first two exons of its 5' UTR are shared with an upstream gene. Variants 2, 3 and 4 encode the same protein (isoform 2).
      Source sequence(s)
      AC118342, DQ079588
      Consensus CDS
      CCDS12786.1
      UniProtKB/TrEMBL
      A2RRH1
      Related
      ENSP00000472474.1, ENST00000595948.5
      Conserved Domains (2) summary
      pfam01593
      Location:91 → 523
      Amino_oxidase; Flavin containing amine oxidoreductase
      pfam13450
      Location:86 → 143
      NAD_binding_8; NAD(P)-binding Rossmann-like domain

    3. NM_001385639.1 → NP_001372568.1  L-amino-acid oxidase isoform 3 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR and coding region, compared to variant 2, and is expressed from a different promoter. The resulting isoform (3) contains a distinct and shorter N-terminus, as compared to isoform 2.
      Source sequence(s)
      AC118342
      UniProtKB/TrEMBL
      A2RRH1
      Conserved Domains (1) summary
      pfam01593
      Location:46 → 464
      Amino_oxidase; Flavin containing amine oxidoreductase

    4. NM_152899.2 → NP_690863.1  L-amino-acid oxidase isoform 1 precursor

      See identical proteins and their annotated locations for NP_690863.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR and coding region, compared to variant 2, and is expressed from a different promoter. The resulting isoform (1) contains a distinct and shorter N-terminus, as compared to isoform 2.
      Source sequence(s)
      AF293462
      Consensus CDS
      CCDS12787.1
      UniProtKB/Swiss-Prot
      Q1WMJ3, Q4GZN1, Q4GZN2, Q6P2Q3, Q8TEM5, Q96RQ8, Q96RQ9
      UniProtKB/TrEMBL
      A2RRH1
      Related
      ENSP00000375702.1, ENST00000391826.7
      Conserved Domains (1) summary
      pfam01593
      Location:69 → 501
      Amino_oxidase; Flavin containing amine oxidoreductase

    5. NM_172374.3 → NP_758962.1  L-amino-acid oxidase isoform 2 precursor

      See identical proteins and their annotated locations for NP_758962.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) encodes the longest isoform (2). The first two exons of its 5' UTR are shared with an upstream gene. Variants 2, 3 and 4 encode the same protein (isoform 2).
      Source sequence(s)
      AC118342, DQ079587
      Consensus CDS
      CCDS12786.1
      UniProtKB/TrEMBL
      A2RRH1
      Related
      ENSP00000342557.2, ENST00000341114.7
      Conserved Domains (2) summary
      pfam01593
      Location:91 → 523
      Amino_oxidase; Flavin containing amine oxidoreductase
      pfam13450
      Location:86 → 143
      NAD_binding_8; NAD(P)-binding Rossmann-like domain

    RNA

    1. NR_047577.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) contains an alternate exon, compared to variant 2. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC011452, AC118342, AJ880389
      Related
      ENST00000601717.5

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      49889654..49929504 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      52889790..52929639 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96RQ9.1 GenPept UniProtKB/Swiss-Prot:Q96RQ9

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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