Tumour necrosis factor domain (IPR006052)
Short name: TNF_dom
Overlapping homologous superfamilies
- Tumour necrosis factor-like domain superfamily (IPR008983)
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.
- 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.