{PDOC00224}
{PS00251; TNF_1}
{PS50049; TNF_2}
{BEGIN}
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* TNF family signature and profile *
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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-alpha) [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-alpha  (LT-alpha)  and  lymphotoxin-beta (LT-beta), 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-alpha is  synthesized  as  a type II membrane protein which then undergoes
post-translational cleavage liberating the extracellular domain. CD27L, CD30L,
CD40L, FASL,  LT-beta,  4-1BBL  and  TRAIL  also appear to be type II membrane
proteins. LT-alpha  is  a  secreted protein. All these cytokines  seem to form
homotrimeric (or heterotrimeric in the case of LT-alpha/beta) 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 beta-strand in the central
section of these proteins.

-Consensus pattern: [LV]-x-[LIVM]-{V}-x-{L}-G-[LIVMF]-Y-[LIVMFY](2)-x(2)-
                    [QEKHL]-[LIVMGT]-x-[LIVMFY]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: 4.

-Sequences known to belong to this class detected by the profile: ALL,  except
 for OX40L.
-Other sequence(s) detected in Swiss-Prot: 2.

-Last update: December 2004 / Pattern and text revised.

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

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