PROSITE documentation PDOC00224TNF 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.
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PROSITE methods (with tools and information) covered by this documentation:
1 | Authors | Peitsch M.C. Jongeneel C.V. |
Title | A 3-D model for the CD40 ligand predicts that it is a compact trimer similar to the tumor necrosis factors. | |
Source | Int. Immunol. 5:233-238(1993). | |
PubMed ID | 8095800 |
2 | Authors | Farrah T. Smith C.A. |
Title | Emerging cytokine family. | |
Source | Nature 358:26-26(1992). | |
PubMed ID | 1377364 | |
DOI | 10.1038/358026b0 |
3 | Authors | Bazan J.F. |
Title | Emerging families of cytokines and receptors. | |
Source | Curr. Biol. 3:603-606(1993). | |
PubMed ID | 15335677 |
4 | Authors | Beutler B. Cerami A. |
Title | The history, properties, and biological effects of cachectin. | |
Source | Biochemistry 27:7575-7582(1988). | |
PubMed ID | 3061461 |
5 | Authors | Vilcek J. Lee T.H. |
Title | Tumor necrosis factor. New insights into the molecular mechanisms of its multiple actions. | |
Source | J. Biol. Chem. 266:7313-7316(1991). | |
PubMed ID | 1850405 |
6 | Authors | Browning 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. |
Title | Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface. | |
Source | Cell 72:847-856(1993). | |
PubMed ID | 7916655 |
7 | Authors | Suda T. Takahashi T. Golstein P. Nagata S. |
Title | Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. | |
Source | Cell 75:1169-1178(1993). | |
PubMed ID | 7505205 |
8 | Authors | Baum 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. |
Title | Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34. | |
Source | EMBO J. 13:3992-4001(1994). | |
PubMed ID | 8076595 |
9 | Authors | Wiley 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. |
Title | Identification and characterization of a new member of the TNF family that induces apoptosis. | |
Source | Immunity 3:673-682(1995). | |
PubMed ID | 8777713 |
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