TNFSFs
Members of the tumor necrosis factor (TNF) family of ligands (TNFSFs) play important roles in various physiologic and pathologic processes, including cell proliferation, differentiation, and death, and modulation of immune responses.
Members
| TNFSF1 | TNFSF2 | TNFSF3 | TNFSF4 | TNFSF5 | TNFSF6 | TNFSF7 | TNFSF8 | TNFSF9 | TNFSF10 |
| TNFSF11 | TNFSF12 | TNFSF13A | TNFSF13B | TNFSF14 | TNFSF15 | TNFSF16 | TNFSF17 | TNFSF18 |
Members
NGF
CD40L
CD137L/4-1BBL
TNF-alpha (TNFA)
CD134L/OX40L
CD27L/CD70
FasL
CD30L
TNF-beta (TNFB)/LT-alpha
LT-beta
TRAIL
EDA
TNF-related ligands usually share a number of common features. These features do not include a high degree of overall amino acid (aa) sequence homology.
With the exception of nerve growth factor (NGF) and TNF-beta (TNFB), all ligands are synthesized as type II transmembrane proteins (extracellular C-terminus) that contain a short cytoplasmic segment (10-80 aa residues) and a relatively long extracellular region (140-215 aa residues).
NGF, which is structurally unrelated to TNF, is included in this superfamily only because of its ability to bind to the TNFRSF low affinity NGF receptor (LNGFR). NGF has a classic signal sequence peptide and is secreted. TNF-beta, in contrast, although also fully secreted, has a primary structure much more related to type II transmembrane proteins.
TNF-beta (TNFB) might be considered as a type II protein with a non-functional, or inefficient, transmembrane segment.
In general, TNFSF members form trimeric structures, and their monomers are composed of beta-strands that orient themselves into a two sheet structure.
As a consequence of the trimeric structure of these molecules, it is suggested that the ligands and receptors of the TNSF and TNFRSF superfamilies undergo "clustering" during signal transduction.
Pathology of TNFSFs
germline mutations of ectodysplasin (EDA) in x-linked ectodermal dysplasia (17924345)
TNFSF4 variants in susceptibility to systemic lupus erythematosus (18059267)
