PROSITE documentation PDOC00224
TNF family signature and profile


The following cytokines can be grouped into a family on the basis of sequence, functional, and structural similarities [1,2,3]:

  • Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-α) [4,5] 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-α (LT-α) and lymphotoxin-β (LT-β), two related cytokines produced by lymphocytes and which are cytotoxic for a wide range of tumor cells in vitro and in vivo [6].
  • 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 [7].
  • 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 [8].
  • TNF-related apoptosis inducing ligand (TRAIL) [9], a cytokine that induces apoptosis [9].

TNF-α is synthesized as a type II membrane protein which then undergoes post-translational cleavage liberating the extracellular domain. CD27L, CD30L, CD40L, FASL, LT-β, 4-1BBL and TRAIL also appear to be type II membrane proteins. LT-α is a secreted protein. All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-α/β) complexes that are recognized by their specific receptors.

As a signature for this family of proteins, we have selected the most conserved region. This region is located in a β-strand in the central section of these proteins.

Last update:

December 2004 / Pattern and text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

TNF_2, PS50049; TNF family profile  (MATRIX)

TNF_1, PS00251; TNF family signature  (PATTERN)


1AuthorsPeitsch M.C. Jongeneel C.V.
TitleA 3-D model for the CD40 ligand predicts that it is a compact trimer similar to the tumor necrosis factors.
SourceInt. Immunol. 5:233-238(1993).
PubMed ID8095800

2AuthorsFarrah T. Smith C.A.
TitleEmerging cytokine family.
SourceNature 358:26-26(1992).
PubMed ID1377364

3AuthorsBazan J.F.
TitleEmerging families of cytokines and receptors.
SourceCurr. Biol. 3:603-606(1993).
PubMed ID15335677

4AuthorsBeutler B. Cerami A.
TitleThe history, properties, and biological effects of cachectin.
SourceBiochemistry 27:7575-7582(1988).
PubMed ID3061461

5AuthorsVilcek J. Lee T.H.
TitleTumor necrosis factor. New insights into the molecular mechanisms of its multiple actions.
SourceJ. Biol. Chem. 266:7313-7316(1991).
PubMed ID1850405

6AuthorsBrowning J.L. Ngam-ek A. Lawton P. DeMarinis J. Tizard R. Chow E.P. Hession C. O'Brine-Greco B. Foley S.F. Ware C.F.
TitleLymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface.
SourceCell 72:847-856(1993).
PubMed ID7916655

7AuthorsSuda T. Takahashi T. Golstein P. Nagata S.
TitleMolecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family.
SourceCell 75:1169-1178(1993).
PubMed ID7505205

8AuthorsBaum P.R. Gayle R.B. III Ramsdell F. Srinivasan S. Sorensen R.A. Watson M.L. Seldin M.F. Baker E. Sutherland G.R. Clifford K.N.
TitleMolecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34.
SourceEMBO J. 13:3992-4001(1994).
PubMed ID8076595

9AuthorsWiley S.R. Schooley K. Smolak P.J. Din W.S. Huang C.-P. Nicholl J.K. Sutherland G.R. Smith T.D. Rauch C. Smith C.A.
TitleIdentification and characterization of a new member of the TNF family that induces apoptosis.
SourceImmunity 3:673-682(1995).
PubMed ID8777713

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