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tumor necrosis factor [TNF]-alpha; tumor necrosis factor ligand superfamily member 2; cachectin (TNF, TNFA, TNFSF2)

Function: - cytokine - binds to TNFRSF1A/TNFR1 & TNFRSF1B/TNFBR - can induce cell death of certain tumor cell lines - potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion - implicated in the induction of cachexia - under certain conditions, can stimulate cell proliferation & induce cell differentiation - the membrane form, but not the soluble form, is phosphorylated on Ser - dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1 - the soluble form derives from the membrane form by proteolytic processing - the membrane-bound form undergoes intramembrane proteolytic cleavage - the membrane-bound form is proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing a TNF intracellular domain (ICD) released in the cytosol for signaling to the nucleus & a TNF C-domain secreted into the extracellular space Structure: - homotrimer - O-glycosylated - glycans contain galactose, N-acetylgalactosamine & N-acetylneuraminic acid - belongs to the tumor necrosis factor family Compartment: - cell membrane, single-pass type 2 membrane protein - soluble form: secreted Expression: - mainly expressed & secreted by macrophages Polymorphism: - polymorphisms in TNF influence susceptibility to hepatitis B infection - polymorphisms in TNF are involved in susceptibility to malaria - polymorphisms in TNF are a cause of susceptibility psoriatic arthritis

Related

infliximab (Remicade) tumor necrosis factor (TNF) alpha in body fluid tumor necrosis factor (TNF) alpha in CSF tumor necrosis factor (TNF) alpha in serum/plasma

General

oligomerizing protein toxin (hazardous material, poison) tumor necrosis factor (TNF) family protein

Properties

CONFIGURATION: trimer SIZE: entity length = 233 aa MW = 26 kD COMPARTMENT: cellular membrane MOTIF: Ser phosphorylation site {S2} proteolytic site {34} transmembrane domain {36-56} MOTIF: proteolytic site {39} proteolytic site {49} proteolytic site {51} proteolytic site {76-77} Ser glycosylation site {S80} cysteine residue {C145} MODIFICATION: cysteine residue {C177} cysteine residue {C177} MODIFICATION: cysteine residue {C145} SECRETED-BY: monocyte macrophage fibroblast T-cell

References

  1. UniProt :accession P01375
  2. Wikipedia; Note: tumor necrosis factor alpha entry http://en.wikipedia.org/wiki/tumor_necrosis_factor-alpha
  3. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/TNFaID319.html
  4. NIEHS-SNPs http://egp.gs.washington.edu/data/tnf/
  5. SeattleSNPs http://pga.gs.washington.edu/data/tnf/
  6. SHMPD; Singapore human mutation and polymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=TNF
  7. Henderson B & Blake S Therapeutic potential of cytokine manipulation TIPS 13:145 1992 PMID: 1589908
  8. Leung L, Cahill CM. TNF-alpha and neuropathic pain--a review. J Neuroinflammation. 2010 Apr 16;7:27 PMID: 20398373

Databases & Figures

OMIM correlations UniProt P01375 Pfam PF00229 Entrez Gene 7124 KEGG correlations signaling pathways: caspases