To improve security and privacy, we are moving our web pages and services from HTTP to HTTPS.
To give users of web services time to transition to HTTPS, we will support separate HTTP and HTTPS services until the end of 2017.
From January 2018 most HTTP traffic will be automatically redirected to HTTPS. [more...]
View this page in https
PROSITE documentation PDOC00224 [for PROSITE entry PS50049]

TNF family signature and profile





Description

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)


References

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
DOI10.1038/358026b0

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



PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)