Homologous Superfamily

Tumour necrosis factor-like domain superfamily (IPR008983)

Short name: Tumour_necrosis_fac-like_dom

Overlapping entries


The tumour necrosis factor (TNF)-like domains are found in both TNF and C1q protein families. Structurally these domains self-associate to make a compact bell-shaped homotrimer, each monomer being composed of an anti-parallel beta-sheet sandwich with a jellyroll topology. Both TNF and C1q family members can be expressed as soluble plasma proteins or as type II membrane-bound proteins.

TNF family members bind extracellularly to cysteine-rich receptors, thereby inducing a clustering of the receptors, which subsequently triggers the intracellular apoptotic cascade. The TNF proteins are important mediators in inflammation, immune responses and cytotoxicity through their interaction with the TNF-R55 and the TNF-R75 cell-surface receptors [PMID: 9442056]. Other TNF family members include the CD40 ligand (C-terminal TNF-like domain) which is involved in the immune response via the CD40 receptor [PMID: 8589998]; TRAIL, which selectively induces apoptosis in tumour cells via DR4 and DR5 receptors [PMID: 10651627]; the RANK ligand (TNFSF11), which triggers osteoclastogenesis via the RANK receptor [PMID: 11733492]; and TALL-1 (soluble domain), which is involved in the immune response via the TACI, BCMA, and BAFF-R receptors [PMID: 11862220].

C1q proteins also contain TNF-like domains. C1q family members include the Adiponectin/ACRP30 (C-terminal TNF-like domain), which regulates metabolism and energy homeostasis [PMID: 22449980], and NC1 (non-collagenous domain 1), the C-terminal TNF-like domain of collagen X, which is crucial for collagen X assembly in bone tissue [PMID: 11839302].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0005515 protein binding

Cellular Component

No terms assigned in this category.

Contributing signatures

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