Conserved Site

Tumour necrosis factor, conserved site (IPR021184)

Short name: TNF_CS

Description

Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities [PMID: 8095800, PMID: 1377364, PMID: 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 [PMID: 2989794, PMID: 3349526]. The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine [PMID: 2268312]. A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers [PMID: 2777790]. Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide [PMID: 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 [PMID: 8095800, PMID: 1377364, PMID: 15335677]:

  • Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-alpha) [PMID: 3061461, PMID: 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 [PMID: 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 [PMID: 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 [PMID: 8076595].
  • TNF-related apoptosis inducing ligand (TRAIL), a cytokine that induces apoptosis [PMID: 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.

This entry represents Tumor Necrosis Factor, conserved site.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns