Tumour necrosis factor, conserved site
IPR021184
Definition
This entry represents α conserved site located in a β-strand in the central section of the protein which is conserved across all members of the Tumor Necrosis Factor family. Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities [[cite:PMID:8095800], [cite:PMID:1377364], [cite: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 [[cite:PMID:2989794], [cite: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 [[cite:PMID:8095800], [cite:PMID:1377364], [cite:PMID:15335677]]: Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-alpha) [[cite:PMID:3061461], [cite: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.
11 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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