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 [ 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 [8589998], TRAIL which selectively induces apoptosis in tumour cells via DR4 and DR5 receptors [10651627], the RANK ligand which triggers osteoclastogenesis via the RANK receptor [11733492], and TALL-1 (soluble domain) which is involved in the immune response via the TACI, BCMA, and BAFF-R receptors [11862220].
C1q proteins also contain TNF-like domains. C1q family members include the serum protein ACRP30 (C-terminal TNF-like domain) which may be involved in energy homeostasis and obesity, and X-NC1 (C-terminal TNF-like domain) which is crucial for collagen X assembly in bone tissue [11839302]. | 
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