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MGP003158

UniProt Annotations

Entry Information
Gene Nametumor necrosis factor
Protein EntryTNFA_HUMAN
UniProt IDP01375
SpeciesHuman
Comments
Comment typeDescription
DiseasePsoriatic arthritis (PSORAS) [MIM:607507]: An inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis). {ECO:0000269|PubMed:12746914}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
FunctionCytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. {ECO:0000269|PubMed:16829952}.
FunctionThe TNF intracellular domain (ICD) form induces IL12 production in dendritic cells. {ECO:0000269|PubMed:16829952}.
InteractionQ8UYL3:crmE (xeno); NbExp=3; IntAct=EBI-359977, EBI-7539950; Q9Y6K9:IKBKG; NbExp=2; IntAct=EBI-359977, EBI-81279; P19438:TNFRSF1A; NbExp=9; IntAct=EBI-359977, EBI-299451; P20333:TNFRSF1B; NbExp=2; IntAct=EBI-359977, EBI-358983;
PolymorphismGenetic variations in TNF are involved in susceptibility to malaria [MIM:611162].
PolymorphismGenetic variations in TNF influence susceptibility to hepatitis B virus (HBV) infection [MIM:610424].
PtmO-glycosylated; glycans contain galactose, N- acetylgalactosamine and N-acetylneuraminic acid. {ECO:0000269|PubMed:8631363}.
PtmThe membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1. {ECO:0000269|PubMed:10205166, ECO:0000269|PubMed:8597870}.
PtmThe soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C- domain 2 secreted into the extracellular space. {ECO:0000269|PubMed:16829951, ECO:0000269|PubMed:16829952, ECO:0000269|PubMed:9034191}.
Sequence CautionSequence=AAF71992.1; Type=Frameshift; Positions=91, 157; Evidence={ECO:0000305}; Sequence=CAA75070.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
SimilarityBelongs to the tumor necrosis factor family. {ECO:0000305}.
Subcellular LocationC-domain 1: Secreted.
Subcellular LocationC-domain 2: Secreted.
Subcellular LocationCell membrane {ECO:0000269|PubMed:16829952}; Single-pass type II membrane protein {ECO:0000269|PubMed:16829952}.
Subcellular LocationTumor necrosis factor, membrane form: Membrane; Single-pass type II membrane protein.
Subcellular LocationTumor necrosis factor, soluble form: Secreted.
SubunitHomotrimer. Interacts with SPPL2B. {ECO:0000269|PubMed:16829951}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TNFaID319.html";
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/tnf/";
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/tnf/";
Web ResourceName=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=TNF";
Web ResourceName=Wikipedia; Note=Tumor necrosis factor alpha entry; URL="http://en.wikipedia.org/wiki/Tumor_necrosis_factor-alpha";
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