Seroatlas · Human Serome Atlas

TNFAIP3

Tumor necrosis factor alpha-induced protein 3

Also known as: A20, OTUD7C, TNAP3_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P21580
Gene: TNFAIP3
Ensembl: ENSG00000118503
Chromosome: 6
Canonical length: 790 aa
Protein class: Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location: Centrosome,Cytosol
Quaternary structure: Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

790 residues, UniProt reviewed canonical sequence.

>P21580|TNFAIP3
     1  MAEQVLPQAL YLSNMRKAVK IRERTPEDIF KPTNGIIHHF KTMHRYTLEM FRTCQFCPQF
    61  REIIHKALID RNIQATLESQ KKLNWCREVR KLVALKTNGD GNCLMHATSQ YMWGVQDTDL
   121  VLRKALFSTL KETDTRNFKF RWQLESLKSQ EFVETGLCYD TRNWNDEWDN LIKMASTDTP
   181  MARSGLQYNS LEEIHIFVLC NILRRPIIVI SDKMLRSLES GSNFAPLKVG GIYLPLHWPA
   241  QECYRYPIVL GYDSHHFVPL VTLKDSGPEI RAVPLVNRDR GRFEDLKVHF LTDPENEMKE
   301  KLLKEYLMVI EIPVQGWDHG TTHLINAAKL DEANLPKEIN LVDDYFELVQ HEYKKWQENS
   361  EQGRREGHAQ NPMEPSVPQL SLMDVKCETP NCPFFMSVNT QPLCHECSER RQKNQNKLPK
   421  LNSKPGPEGL PGMALGASRG EAYEPLAWNP EESTGGPHSA PPTAPSPFLF SETTAMKCRS
   481  PGCPFTLNVQ HNGFCERCHN ARQLHASHAP DHTRHLDPGK CQACLQDVTR TFNGICSTCF
   541  KRTTAEASSS LSTSLPPSCH QRSKSDPSRL VRSPSPHSCH RAGNDAPAGC LSQAARTPGD
   601  RTGTSKCRKA GCVYFGTPEN KGFCTLCFIE YRENKHFAAA SGKVSPTASR FQNTIPCLGR
   661  ECGTLGSTMF EGYCQKCFIE AQNQRFHEAK RTEEQLRSSQ RRDVPRTTQS TSRPKCARAS
   721  CKNILACRSE ELCMECQHPN QRMGPGAHRG EPAPEDPPKQ RCRAPACDHF GNAKCNGYCN
   781  ECFQFKQMYG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNFAIP3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.4
Highest tissue expression: 394 nTPM

Expression across tissuesHPA

Tissue

bone marrow: 394 nTPM
urinary bladder: 146 nTPM
appendix: 86 nTPM
ovary: 65 nTPM
thymus: 60 nTPM
lymph node: 55 nTPM

Single-cell type

neutrophils: 5,956 nCPM
innate lymphoid cells: 2,537 nCPM
mast cells: 2,207 nCPM
endometrial luminal cells: 1,915 nCPM
endometrial glandular cells: 1,903 nCPM
monocytes: 1,643 nCPM

Immune cell

MAIT T-cell: 15 nTPM
T-reg: 12 nTPM
gdT-cell: 12 nTPM
memory CD4 T-cell: 11 nTPM
memory CD8 T-cell: 11 nTPM
plasmacytoid DC: 9.2 nTPM

Brain region

cerebral cortex: 25 nTPM
choroid plexus: 13 nTPM
thalamus: 10 nTPM
spinal cord: 7.8 nTPM
medulla oblongata: 7.5 nTPM
pons: 7.3 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TNFAIP3.

Disease | AllUniProt

Conditions TNFAIP3 is implicated in, by any mechanism.

Autoinflammatory syndrome, familial, Behcet-like 1 (AIFBL1) MIM:616744

Disease | GeneticClinVar

91 pathogenic / likely-pathogenic of 740 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Autoinflammatory syndrome, familial, Behcet-like 1
Autoinflammatory syndrome, familial, Behcet-like
Neoplasm
Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.2
gnomAD pLI: 1
gnomAD missense Z: 1.45
DepMap mean gene effect: 0.01
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of TNFAIP3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads TNFAIP3 as an antibody target. Whether an autoantibody or antibody against TNFAIP3 could matter depends on whether native TNFAIP3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

TNFAIP3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label TNFAIP3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Loading the interactive Seroatlas protein explorer...