TNF

Tumour necrosis factor family.
TNF
SMART accession number:SM00207
Description: Family of cytokines that form homotrimeric or heterotrimeric complexes. TNF mediates mature T-cell receptor-induced apoptosis through the p75 TNF receptor.
Interpro abstract (IPR006052):

Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities [(PUBMED:8095800), (PUBMED:1377364), (PUBMED:15335677)]. Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia [(PUBMED:2989794), (PUBMED:3349526)]. The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine [(PUBMED:2268312)]. A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers [(PUBMED:2777790)]. Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide [(PUBMED:2777790)].

There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors.

The following cytokines can be grouped into a family on the basis of sequence, functional, and structural similarities [(PUBMED:8095800), (PUBMED:1377364), (PUBMED:15335677)]:

  • Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-alpha) [(PUBMED:3061461), (PUBMED:1850405)] is a cytokine which has a wide variety of functions. It can cause cytolysis of certain tumor cell lines; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion; finally, it can stimulate cell proliferation and induce cell differentiation under certain conditions.
  • Lymphotoxin-alpha (LT-alpha) and lymphotoxin-beta (LT-beta), two related cytokines produced by lymphocytes and which are cytotoxic for a wide range of tumor cells in vitro and in vivo [(PUBMED:7916655)].
  • T cell antigen gp39 (CD40L), a cytokine which seems to be important in B-cell development and activation.
  • CD27L, a cytokine which plays a role in T-cell activation. It induces the proliferation of costimulated T cells and enhances the generation of cytolytic T cells.
  • CD30L, a cytokine which induces proliferation of T cells.
  • FASL, a cytokine involved in cell death [(PUBMED:7505205)].
  • 4-1BBL, a inducible T cell surface molecule that contributes to T-cell stimulation.
  • OX40L, a cytokine that co-stimulates T cell proliferation and cytokine production [(PUBMED:8076595)].
  • TNF-related apoptosis inducing ligand (TRAIL), a cytokine that induces apoptosis [(PUBMED:8777713)].
  • TNF-alpha is synthesised as a type II membrane protein which then undergoes post-translational cleavage liberating the extracellular domain. CD27L, CD30L, CD40L, FASL, LT-beta, 4-1BBL and TRAIL also appear to be type II membrane proteins. LT-alpha is a secreted protein.

All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors. The PROSITE pattern for this family is located in a beta-strand in the central section of the protein which is conserved across all members.

GO process:immune response (GO:0006955)
GO component:membrane (GO:0016020)
GO function:tumor necrosis factor receptor binding (GO:0005164)
Family alignment:
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There are 1853 TNF domains in 1841 proteins in SMART's nrdb database.

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