TNF Tumour necrosis factor family.
SMART ACC:	SM000207
Description:	Family of cytokines that form homotrimeric or heterotrimeric complexes. TNF mediates mature T-cell receptor-induced apoptosis through the p75 TNF receptor.
InterPro ACC:	IPR006052
InterPro abstract:	The following cytokines can be grouped into a family on the basis of sequence, functional, and structural similarities [ PUBMED:8095800 PUBMED:1377364 PUBMED:15335677 … expand 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. 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. collapse
GO process:	immune response (GO:0006955)
GO component:	membrane (GO:0016020)
GO function:	tumor necrosis factor receptor binding (GO:0005164)
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 5 212 TNF domains in 5 186 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing TNF domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing TNF domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Relevant references for this domain

Primary literature for the TNF domain is listed below. Automatically-derived, secondary literature is also available.

Disease genes where sequence variants are found in this domain

UniRef sequences and OMIM curated human diseases associated with missense mutations within the TNF domain.

Protein	Description	Disease / phenotype
CD40L_HUMAN		OMIM:308230 : Immunodeficiency, X-linked, with hyper-IgM

KEGG pathways involving proteins which contain this domain

This information is based on the mapping of SMART genomic protein database to KEGG orthologous groups. Percentages are related to the number of proteins containing a TNF domain which could be assigned to a KEGG orthologous group, and not all proteins containing TNF domains. Please note that proteins can be included in multiple pathways, ie. the numbers below will not add to 100%.

KEGG pathways

KEGG orthologous groups

Some of these KOs are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

3D structures in PDB containing this domain

Links to other resources describing this domain

InterPro	IPR006052
PROSITE	TNF_DOMAIN
Pfam	TNF