Tumour necrosis factor alpha (IPR002959)

Short name: TNF_alpha

Overlapping homologous superfamilies

Family relationships


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 structure of human TNF has been determined to 2.9 A using X-ray crystallography. The protein is trimeric, each subunit consisting of an anti-parallel beta-sandwich. The subunits trimerise via a novel edge-to-face packing of beta-sheets [PMID: 2922050]. It is believed that each TNF molecule has three receptor-interaction sites (between the three subunits), thus allowing signal transmission by receptor clustering [PMID: 2009860].

This entry represents TNF-alpha, which is a soluble cytokine with a wide variety of functions: it causes damage to tumour cells but has no effect on normal cells; 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; and it can stimulate cell proliferation and induce cell differentiation under certain conditions.

GO terms

Biological Process

GO:0006955 immune response

Molecular Function

GO:0005164 tumor necrosis factor receptor binding

Cellular Component

GO:0016020 membrane

Contributing signatures

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