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TNFAIP3 TNF alpha induced protein 3 [ Homo sapiens (human) ]

Gene ID: 7128, updated on 17-Oct-2021

Summary

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Official Symbol
TNFAIP3provided by HGNC
Official Full Name
TNF alpha induced protein 3provided by HGNC
Primary source
HGNC:HGNC:11896
See related
Ensembl:ENSG00000118503 MIM:191163
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
A20; AISBL; OTUD7C; TNFA1P2
Summary
This gene was identified as a gene whose expression is rapidly induced by the tumor necrosis factor (TNF). The protein encoded by this gene is a zinc finger protein and ubiqitin-editing enzyme, and has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. The encoded protein, which has both ubiquitin ligase and deubiquitinase activities, is involved in the cytokine-mediated immune and inflammatory responses. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2012]
Expression
Broad expression in bone marrow (RPKM 156.2), appendix (RPKM 61.9) and 14 other tissues See more
Orthologs
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Genomic context

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See TNFAIP3 in Genome Data Viewer
Location:
6q23.3
Exon count:
13
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (137866317..137883312)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (138188396..138204449)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 2539 Neighboring gene wound and keratinocyte migration associated lncRNA 2 Neighboring gene uncharacterized LOC107986649 Neighboring gene long intergenic non-protein coding RNA 2528 Neighboring gene uncharacterized LOC107986545

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. Down-regulation of A20 promotes immune escape of lung adenocarcinomas. Breitenecker K, et al. Sci Transl Med, 2021 Jul 7. PMID 34233950,
  2. A20 regulates inflammation through autophagy mediated by NF-κB pathway in human nucleus pulposus cells and ameliorates disc degeneration in vivo. Zhang Y, et al. Biochem Biophys Res Commun, 2021 Apr 16. PMID 33677390
  3. Functional analysis of novel A20 variants in patients with atypical inflammatory diseases. Kadowaki S, et al. Arthritis Res Ther, 2021 Feb 6. PMID 33549127, Free PMC Article
  4. Immunohistochemical Assessment of TNFAIP3/A20 Expression Correlates With Early Tumorigenesis in Breast Cancer. Sharif-Askari FS, et al. Anticancer Res, 2021 Feb. PMID 33517278
  5. A20 regulates the therapeutic effect of anti-PD-1 immunotherapy in melanoma. Guo W, et al. J Immunother Cancer, 2020 Dec. PMID 33298620, Free PMC Article

See all (472) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Haploinsufficiency of A20 (HA20): updates on the genetics, phenotype, pathogenesis and treatment.
    Title: Haploinsufficiency of A20 (HA20): updates on the genetics, phenotype, pathogenesis and treatment.
  2. RNF31 mediated ubiquitination of A20 aggravates inflammation and hepatocyte apoptosis through the TLR4/MyD88/NF-kappaB signaling pathway.
    Title: RNF31 mediated ubiquitination of A20 aggravates inflammation and hepatocyte apoptosis through the TLR4/MyD88/NF-κB signaling pathway.
  3. A20 regulates the therapeutic effect of anti-PD-1 immunotherapy in melanoma.
    Title: A20 regulates the therapeutic effect of anti-PD-1 immunotherapy in melanoma.
  4. Haploinsufficiency of A20 Due to Novel Mutations in TNFAIP3.
    Title: Haploinsufficiency of A20 Due to Novel Mutations in TNFAIP3.
  5. A20 regulates inflammation through autophagy mediated by NF-kappaB pathway in human nucleus pulposus cells and ameliorates disc degeneration in vivo.
    Title: A20 regulates inflammation through autophagy mediated by NF-κB pathway in human nucleus pulposus cells and ameliorates disc degeneration in vivo.
  6. gamma-Aminobutyric Acid Promotes Osteogenic Differentiation of Mesenchymal Stem Cells by Inducing TNFAIP3.
    Title: γ-Aminobutyric Acid Promotes Osteogenic Differentiation of Mesenchymal Stem Cells by Inducing TNFAIP3.
  7. Functional analysis of novel A20 variants in patients with atypical inflammatory diseases.
    Title: Functional analysis of novel A20 variants in patients with atypical inflammatory diseases.
  8. Mesenchymal stem cell-originated exosomal lncRNA HAND2-AS1 impairs rheumatoid arthritis fibroblast-like synoviocyte activation through miR-143-3p/TNFAIP3/NF-kappaB pathway.
    Title: Mesenchymal stem cell-originated exosomal lncRNA HAND2-AS1 impairs rheumatoid arthritis fibroblast-like synoviocyte activation through miR-143-3p/TNFAIP3/NF-κB pathway.
  9. Tumour Necrosis Factor Alpha-induced Protein 3 Negatively Regulates Cutibacterium acnes-induced Innate Immune Events in Epidermal Keratinocytes.
    Title: Tumour Necrosis Factor Alpha-induced Protein 3 Negatively Regulates Cutibacterium acnes-induced Innate Immune Events in Epidermal Keratinocytes.
  10. Down-regulation of A20 promotes immune escape of lung adenocarcinomas.
    Title: Down-regulation of A20 promotes immune escape of lung adenocarcinomas.
Submit: New GeneRIF Correction See all GeneRIFs (354)

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

Associated conditions

Description Tests
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
GeneReviews: Not available
A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23.
GeneReviews: Not available
A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility.
GeneReviews: Not available
A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.
GeneReviews: Not available
Association of genome-wide variation with highly sensitive cardiac troponin-T levels in European Americans and Blacks: a meta-analysis from atherosclerosis risk in communities and cardiovascular health studies.
GeneReviews: Not available
Autoinflammatory syndrome, familial, Behcet-like
MedGen: C4225218 OMIM: 616744 GeneReviews: Not available
Compare labs
Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus.
GeneReviews: Not available
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
GeneReviews: Not available
Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus.
GeneReviews: Not available
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
GeneReviews: Not available
Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways.
GeneReviews: Not available
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
GeneReviews: Not available
Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.
GeneReviews: Not available
Multiple common variants for celiac disease influencing immune gene expression.
GeneReviews: Not available
Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study.
GeneReviews: Not available
Two independent alleles at 6q23 associated with risk of rheumatoid arthritis.
GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 and the viral protein Tat modulate the expression of tumor necrosis factor, alpha-induced protein 3 (TNFAIP3) in immature dendritic cells and monocyte-derived macrophages PubMed

Go to the HIV-1, Human Interaction Database

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

Clone Names

  • MGC104522, MGC138687, MGC138688

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables K63-linked polyubiquitin modification-dependent protein binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables Lys63-specific deubiquitinase activity EXP
Inferred from Experiment
more info
 PubMed 
enables Lys63-specific deubiquitinase activity TAS
Traceable Author Statement
more info
  
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables kinase binding IEA
Inferred from Electronic Annotation
more info
  
enables protease binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein C-terminus binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein self-association IDA
Inferred from Direct Assay
more info
 PubMed 
enables thiol-dependent deubiquitinase IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables thiol-dependent deubiquitinase IDA
Inferred from Direct Assay
more info
 PubMed 
enables thiol-dependent deubiquitinase IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables thiol-dependent deubiquitinase TAS
Traceable Author Statement
more info
 PubMed 
enables ubiquitin binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables zinc ion binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in B-1 B cell homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in cell migration IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in cellular response to hydrogen peroxide ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to lipopolysaccharide IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cytoskeleton organization IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in establishment of protein localization to vacuole IEA
Inferred from Electronic Annotation
more info
  
involved_in inflammatory response IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of B cell activation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of CD40 signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of I-kappaB kinase/NF-kappaB signaling IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of bone resorption NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in negative regulation of chronic inflammatory response IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of cyclin-dependent protein serine/threonine kinase activity IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of endothelial cell apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of extrinsic apoptotic signaling pathway via death domain receptors IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of inflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of innate immune response ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_or_within negative regulation of interleukin-1 beta production IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of interleukin-2 production IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of interleukin-6 production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of osteoclast proliferation NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in negative regulation of protein ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of smooth muscle cell proliferation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of toll-like receptor 2 signaling pathway NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in negative regulation of toll-like receptor 3 signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of toll-like receptor 4 signaling pathway NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in negative regulation of toll-like receptor 5 signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of tumor necrosis factor production ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in nucleotide-binding oligomerization domain containing signaling pathway TAS
Traceable Author Statement
more info
  
involved_in positive regulation of Wnt signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in positive regulation of cellular protein catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of hepatocyte proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein K11-linked deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein K29-linked deubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in protein K33-linked deubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in protein K48-linked deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein K48-linked ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein K63-linked deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein deubiquitination TAS
Traceable Author Statement
more info
 PubMed 
involved_in protein deubiquitination involved in ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in regulation of defense response to virus by host NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in regulation of germinal center formation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of tumor necrosis factor-mediated signaling pathway TAS
Traceable Author Statement
more info
  
involved_in regulation of vascular wound healing NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in response to molecule of bacterial origin IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to muramyl dipeptide IEA
Inferred from Electronic Annotation
more info
  
involved_in tolerance induction to lipopolysaccharide IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in lysosome IEA
Inferred from Electronic Annotation
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
tumor necrosis factor alpha-induced protein 3
Names
OTU domain-containing protein 7C
putative DNA-binding protein A20
tumor necrosis factor inducible protein A20
tumor necrosis factor, alpha induced protein 3
zinc finger protein A20
NP_001257436.1
NP_001257437.1
NP_006281.1
XP_005267176.1
XP_006715618.1
XP_011534397.1
XP_011534398.1
XP_024302300.1
XP_024302301.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

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_032761.1 RefSeqGene

    Range
    4816..20869
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001270507.2 → NP_001257436.1  tumor necrosis factor alpha-induced protein 3

    See identical proteins and their annotated locations for NP_001257436.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. All three variants encode the same protein.
    Source sequence(s)
    CB528739, DB143089, M59465
    Consensus CDS
    CCDS5187.1
    UniProtKB/Swiss-Prot
    P21580
    Conserved Domains (2) summary
    smart00259
    Location:759 → 784
    ZnF_A20; A20-like zinc fingers
    pfam02338
    Location:98 → 257
    OTU; OTU-like cysteine protease

  2. NM_001270508.2 → NP_001257437.1  tumor necrosis factor alpha-induced protein 3

    See identical proteins and their annotated locations for NP_001257437.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. All three variants encode the same protein.
    Source sequence(s)
    CB528739, HY009939, M59465
    Consensus CDS
    CCDS5187.1
    UniProtKB/Swiss-Prot
    P21580
    Related
    ENSP00000481570.1, ENST00000612899.5
    Conserved Domains (2) summary
    smart00259
    Location:759 → 784
    ZnF_A20; A20-like zinc fingers
    pfam02338
    Location:98 → 257
    OTU; OTU-like cysteine protease

  3. NM_006290.4 → NP_006281.1  tumor necrosis factor alpha-induced protein 3

    See identical proteins and their annotated locations for NP_006281.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. All three variants encode the same protein.
    Source sequence(s)
    CB528739, HY085289, M59465
    Consensus CDS
    CCDS5187.1
    UniProtKB/Swiss-Prot
    P21580
    Related
    ENSP00000237289.4, ENST00000237289.8
    Conserved Domains (2) summary
    smart00259
    Location:759 → 784
    ZnF_A20; A20-like zinc fingers
    pfam02338
    Location:98 → 257
    OTU; OTU-like cysteine protease

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

    Range
    137866317..137883312
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011536095.1 → XP_011534397.1  tumor necrosis factor alpha-induced protein 3 isoform X1

    See identical proteins and their annotated locations for XP_011534397.1

    UniProtKB/Swiss-Prot
    P21580
    Conserved Domains (2) summary
    smart00259
    Location:759 → 784
    ZnF_A20; A20-like zinc fingers
    pfam02338
    Location:98 → 257
    OTU; OTU-like cysteine protease

  2. XM_011536096.2 → XP_011534398.1  tumor necrosis factor alpha-induced protein 3 isoform X2

    Conserved Domains (2) summary
    smart00259
    Location:475 → 500
    ZnF_A20; A20-like zinc fingers
    pfam02338
    Location:98 → 257
    OTU; OTU-like cysteine protease

  3. XM_024446532.1 → XP_024302300.1  tumor necrosis factor alpha-induced protein 3 isoform X1

    Conserved Domains (2) summary
    smart00259
    Location:759 → 784
    ZnF_A20; A20-like zinc fingers
    pfam02338
    Location:98 → 257
    OTU; OTU-like cysteine protease

  4. XM_024446533.1 → XP_024302301.1  tumor necrosis factor alpha-induced protein 3 isoform X1

    Conserved Domains (2) summary
    smart00259
    Location:759 → 784
    ZnF_A20; A20-like zinc fingers
    pfam02338
    Location:98 → 257
    OTU; OTU-like cysteine protease

  5. XM_005267119.1 → XP_005267176.1  tumor necrosis factor alpha-induced protein 3 isoform X1

    See identical proteins and their annotated locations for XP_005267176.1

    UniProtKB/Swiss-Prot
    P21580
    Related
    ENSP00000481454.1, ENST00000620204.3
    Conserved Domains (2) summary
    smart00259
    Location:759 → 784
    ZnF_A20; A20-like zinc fingers
    pfam02338
    Location:98 → 257
    OTU; OTU-like cysteine protease

  6. XM_006715555.1 → XP_006715618.1  tumor necrosis factor alpha-induced protein 3 isoform X3

    Conserved Domains (2) summary
    smart00259
    Location:546 → 571
    ZnF_A20; A20-like zinc fingers
    cl19932
    Location:6 → 44
    OTU; OTU-like cysteine protease
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P21580.1 GenPept UniProtKB/Swiss-Prot:P21580

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