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

Gene ID: 7128, updated on 3-Jan-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
109.20201120 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (137866317..137883312)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (138188325..138204451)

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. [Effect of Regulating A20 Expression on NF-κB Expression and Biological Characteristics of Jurkat Cells]. Wang Z, et al. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2020 Aug. PMID 32798389
  2. Identification of TNFAIP3 as relapse biomarker and potential therapeutic target for MOG antibody associated diseases. Saxena S, et al. Sci Rep, 2020 Jul 24. PMID 32709905, Free PMC Article
  3. High throughput sequencing reveals high specificity of TNFAIP3 mutations in ocular adnexal marginal zone B-cell lymphomas. Vela V, et al. Hematol Oncol, 2020 Aug. PMID 32012328
  4. A20 as an immune tolerance factor can determine islet transplant outcomes. Zammit NW, et al. JCI Insight, 2019 Nov 1. PMID 31581152, Free PMC Article
  5. TNFAIP3 Gene Polymorphisms in Three Common Autoimmune Diseases: Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Primary Sjogren Syndrome-Association with Disease Susceptibility and Clinical Phenotypes in Italian Patients. Ciccacci C, et al. J Immunol Res, 2019. PMID 31534975, Free PMC Article

See all (442) 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. 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.
  2. 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.
  3. A20 as an immune tolerance factor can determine islet transplant outcomes.
    Title: A20 as an immune tolerance factor can determine islet transplant outcomes.
  4. 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.
  5. 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.
  6. [Effect of Regulating A20 Expression on NF-kappaB Expression and Biological Characteristics of Jurkat Cells].
    Title: [Effect of Regulating A20 Expression on NF-κB Expression and Biological Characteristics of Jurkat Cells].
  7. High throughput sequencing reveals high specificity of TNFAIP3 mutations in ocular adnexal marginal zone B-cell lymphomas.
    Title: High throughput sequencing reveals high specificity of TNFAIP3 mutations in ocular adnexal marginal zone B-cell lymphomas.
  8. Study found de novo frameshift mutation in TNFAIP3 in neuropsychiatric systemic lupus erythematosus patient and using cell culture experiments with recombinant mutated protein demonstrated that mutant TNFAIP3 in patients could cause dysfunction of barrier maintenance which led to leakage of inflammatory cytokines from peripheral into CNS, while microglia exacerbated the neuroinflammation by secreting cytokines.
    Title: A De Novo Frameshift Mutation in TNFAIP3 Impairs A20 Deubiquitination Function to Cause Neuropsychiatric Systemic Lupus Erythematosus.
  9. Our results demonstrated that rs610604 in TNFAIP3 polymorphism was significantly associated with psoriasis risk using random-effect model (G vs. T, OR = 1.19, 95% CI: 1.09-1.31, P = 0.0002), and a significant association between rs17728338 in TNIP1 polymorphism and psoriasis vulnerability using fixed-effect model (A vs. G, OR = 1.69, 95% CI:1.58-1.80, P < 0.00001).
    Title: Association of rs610604 in TNFAIP3 and rs17728338 in TNIP1 gene polymorphisms with psoriasis susceptibility: a meta-analysis of case-control studies.
  10. the A20-ACSL4 axis plays important roles in erastin-induced endothelial ferroptosis.
    Title: miRNA-17-92 protects endothelial cells from erastin-induced ferroptosis through targeting the A20-ACSL4 axis.
Submit: New GeneRIF Correction See all GeneRIFs (326)

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&amp;#x000c3;&amp;#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)

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
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 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
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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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 109.20201120

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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