| Literature References | 1. ARMITAGE, R.
Tumor necrosis factor receptor superfamily members and their ligands.
CURR.OPIN.IMMUNOL. 6 407-413 (1994).
2. BANNER D., D'ARCY, A., JAMES, W., GENTZ, R., SCHOENFELD, H., BROGER, C.,
LOETSCHER, H. AND LESSLAUER, W.
Crystal structure of the soluble human 55 kD TNF receptor-human TNF-beta
complex: implications for TNF receptor activation.
CELL 73 431-445 (1993).
3. WU, H.
Assembly of post-receptor signaling complexes for the tumor necrosis factor
receptor superfamily.
ADV.PROTEIN CHEM. 68 225-279 (2004).
4. LOCKSLEY, R., KILLEEN, N. AND LENARDO, M.
The TNF and TNF Receptor Superfamilies: Integrating Mammalian Biology.
CELL 104 487-501 (2001).
5. GRAVESTEIN, L. AND BORST, J.
Tumor necrosis factor receptor family members in the immune system.
SEMIN.IMMUNOL. 10 423-434 (1998).
6. LOENEN, W.
D27 and (TNFR) relatives in the immune system: their role in health and
disease.
SEMIN.IMMUNOL. 10 417-422 (1998).
7. WEINBERG, A., EVANS, D., THALHOFER, C., SHI, T. AND PRELL, R.
The generation of T cell memory: a review describing the molecular and
cellular events following OX40 (CD134) engagement.
J.LEUKOC.BIOL. 75 962-972 (2004).
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| Documentation | The tumour necrosis factor (TNF) receptor (TNFR) superfamily comprises more
than 20 type-I transmembrane proteins. Family members are defined based on
similarity in their extracellular domain - a region that contains many
cysteine residues arranged in a specific repetitive pattern [1]. The
cysteines allow formation of an extended rod-like structure, responsible for
ligand binding [2].
Upon receptor activation, different intracellular signalling complexes are
assembled for different members of the TNFR superfamily, depending on their
intracellular domains and sequences [3]. Activation of TNFRs can therefore
induce a range of disparate effects, including cell proliferation,
differentiation, survival, or apoptotic cell death, depending upon the
receptor involved [4,5].
TNFRs are widely distributed and play important roles in many crucial
biological processes, such as lymphoid and neuronal development, innate and
adaptive immunity, and maintenance of cellular homeostasis [3]. Drugs that
manipulate their signalling have potential roles in the prevention and
treatment of many diseases, such as viral infections, coronary heart
disease, transplant rejection, and immune disease [6].
TNF receptor 4 (also known as OX40 and CD134 antigen) is expressed primarily
on activated CD4(+) T cells. Activation of the receptor increases the
proinflammatory activity of these cells and enhances their long-term
survival [7].
TNFACTORR4 is a 3-element fingerprint that provides a signature for tumour
necrosis factor receptor 4. The fingerprint was derived from an initial
alignment of 2 sequences: the motifs were drawn from conserved regions
either side of the transmembrane domain, focusing on those sections that
characterise TNF receptor 4 but distinguish it from other TNF receptor
subtypes - motif 1 resides within the extracellular N-terminal region;
and motifs 2 and 3 lie within the intracellular C-terminal region. Two
iterations on SPTR55_38f were required to reach convergence, at which point
a true set comprising 5 sequences was identified.
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