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

Summary

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: mouse all
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Genomic context

Location:: 6q23.3

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
109.20201120	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_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Immune Regulation of TNFAIP3 in Psoriasis through Its Association with Th1 and Th17 Cell Differentiation and p38 Activation.
Title: Immune Regulation of TNFAIP3 in Psoriasis through Its Association with Th1 and Th17 Cell Differentiation and p38 Activation.
A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma.
Title: A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma.
Immunohistochemical Assessment of TNFAIP3/A20 Expression Correlates With Early Tumorigenesis in Breast Cancer.
Title: Immunohistochemical Assessment of TNFAIP3/A20 Expression Correlates With Early Tumorigenesis in Breast Cancer.
A20 Promotes Ripoptosome Formation and TNF-Induced Apoptosis via cIAPs Regulation and NIK Stabilization in Keratinocytes.
Title: A20 Promotes Ripoptosome Formation and TNF-Induced Apoptosis via cIAPs Regulation and NIK Stabilization in Keratinocytes.
Lack of association of TNFA, TNFRSF1B and TNFAIP3 gene polymorphisms with response to anti-tumor necrosis factor therapy in Japanese patients with psoriasis.
Title: Lack of association of TNFA, TNFRSF1B and TNFAIP3 gene polymorphisms with response to anti-tumor necrosis factor therapy in Japanese patients with psoriasis.
Identification of TNFAIP3 as relapse biomarker and potential therapeutic target for MOG antibody associated diseases.
Title: Identification of TNFAIP3 as relapse biomarker and potential therapeutic target for MOG antibody associated diseases.
TNFalpha-Signaling Modulates the Kinase Activity of Human Effector Treg and Regulates IL-17A Expression.
Title: TNFα-Signaling Modulates the Kinase Activity of Human Effector Treg and Regulates IL-17A Expression.
A20 as an immune tolerance factor can determine islet transplant outcomes.
Title: A20 as an immune tolerance factor can determine islet transplant outcomes.
TNFAIP3 genetic polymorphisms reduce ankylosing spondylitis risk in Eastern Chinese Han population.
Title: TNFAIP3 genetic polymorphisms reduce ankylosing spondylitis risk in Eastern Chinese Han population.
Role of deleterious single nucleotide variants in the coding regions of TNFAIP3 for Japanese autoimmune hepatitis with cirrhosis.
Title: Role of deleterious single nucleotide variants in the coding regions of TNFAIP3 for Japanese autoimmune hepatitis with cirrhosis.

Submit: New GeneRIF Correction See all GeneRIFs (331)

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 Sj&#x000c3;&#x000b6;gren'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)

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

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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

STS-M59465 (e-PCR)
- UniSTS:50983

TNFAIP3_431 (e-PCR)
- UniSTS:277825

D6S2077 (e-PCR)
- UniSTS:56662

PMC152246P3 (e-PCR)
- UniSTS:271205

PMC355833P1 (e-PCR)
- UniSTS:273253

PMC355833P2 (e-PCR)
- UniSTS:273254

PMC355833P3 (e-PCR)
- UniSTS:273255

D6S1833 (e-PCR)
- UniSTS:51875

PMC135646P1 (e-PCR)
- UniSTS:270765

PMC135646P2 (e-PCR)
- UniSTS:270766

D6S1858 (e-PCR)
- UniSTS:42178

SHGC-132182 (e-PCR)
- UniSTS:170697

G10608 (e-PCR)
- UniSTS:79322

STS-R70479 (e-PCR)
- UniSTS:6382

Homology

Homologs of the TNFAIP3 gene: The TNFAIP3 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Orthologs from Annotation Pipeline: 345 organisms have orthologs with human gene TNFAIP3
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA binding	IEA Inferred from Electronic Annotation more info
K63-linked polyubiquitin modification-dependent protein binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Lys63-specific deubiquitinase activity	EXP Inferred from Experiment more info	PubMed
Lys63-specific deubiquitinase activity	TAS Traceable Author Statement more info
cysteine-type peptidase activity	IEA Inferred from Electronic Annotation more info
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
kinase binding	IEA Inferred from Electronic Annotation more info
protease binding	IPI Inferred from Physical Interaction more info	PubMed
protein C-terminus binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein self-association	IDA Inferred from Direct Assay more info	PubMed
thiol-dependent ubiquitin-specific protease activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
thiol-dependent ubiquitin-specific protease activity	IDA Inferred from Direct Assay more info	PubMed
thiol-dependent ubiquitin-specific protease activity	IMP Inferred from Mutant Phenotype more info	PubMed
thiol-dependent ubiquitin-specific protease activity	TAS Traceable Author Statement more info	PubMed
ubiquitin binding	IPI Inferred from Physical Interaction more info	PubMed
ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed
zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
B-1 B cell homeostasis	ISS Inferred from Sequence or Structural Similarity more info
apoptotic process	IEA Inferred from Electronic Annotation more info
cell migration	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular response to hydrogen peroxide	ISS Inferred from Sequence or Structural Similarity more info
cellular response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info	PubMed
establishment of protein localization to vacuole	IEA Inferred from Electronic Annotation more info
inflammatory response	IEA Inferred from Electronic Annotation more info
negative regulation of B cell activation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of CD40 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of I-kappaB kinase/NF-kappaB signaling	IDA Inferred from Direct Assay more info	PubMed
negative regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of bone resorption	NAS Non-traceable Author Statement more info	PubMed
negative regulation of chronic inflammatory response	IEA Inferred from Electronic Annotation more info
negative regulation of cyclin-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
negative regulation of endothelial cell apoptotic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	IDA Inferred from Direct Assay more info	PubMed
negative regulation of inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of innate immune response	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of interleukin-1 beta production	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of interleukin-2 production	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of interleukin-6 production	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of osteoclast proliferation	NAS Non-traceable Author Statement more info	PubMed
negative regulation of protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
negative regulation of smooth muscle cell proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of toll-like receptor 2 signaling pathway	NAS Non-traceable Author Statement more info	PubMed
negative regulation of toll-like receptor 3 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
negative regulation of toll-like receptor 4 signaling pathway	NAS Non-traceable Author Statement more info	PubMed
negative regulation of toll-like receptor 5 signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of type I interferon production	TAS Traceable Author Statement more info
nucleotide-binding oligomerization domain containing signaling pathway	TAS Traceable Author Statement more info
positive regulation of Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of cellular protein catabolic process	IEA Inferred from Electronic Annotation more info
positive regulation of hepatocyte proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
protein K11-linked deubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein K29-linked deubiquitination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein K33-linked deubiquitination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein K48-linked deubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein K48-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein K63-linked deubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein deubiquitination	TAS Traceable Author Statement more info	PubMed
protein deubiquitination involved in ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein phosphopantetheinylation	IEA Inferred from Electronic Annotation more info
regulation of defense response to virus by host	NAS Non-traceable Author Statement more info	PubMed
regulation of germinal center formation	ISS Inferred from Sequence or Structural Similarity more info
regulation of tumor necrosis factor-mediated signaling pathway	TAS Traceable Author Statement more info
regulation of vascular wound healing	NAS Non-traceable Author Statement more info	PubMed
response to molecule of bacterial origin	IDA Inferred from Direct Assay more info	PubMed
response to muramyl dipeptide	IEA Inferred from Electronic Annotation more info
tolerance induction to lipopolysaccharide	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytosol	TAS Traceable Author Statement more info
extracellular exosome	HDA more info	PubMed
lysosome	IEA Inferred from Electronic Annotation more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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

EC 3.4.19.12

NP_001257437.1

EC 3.4.19.12

NP_006281.1

EC 3.4.19.12

XP_005267176.1

EC 3.4.19.12

XP_006715618.1

EC 3.4.19.12

XP_011534397.1

EC 3.4.19.12

XP_011534398.1

EC 3.4.19.12

XP_024302300.1

EC 3.4.19.12

XP_024302301.1

EC 3.4.19.12

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

NG_032761.1 RefSeqGene

Range

4816..20869

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p13 Primary Assembly

Range

137866317..137883312

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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
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
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