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PR01975

Identifier
TNFACTORR11B  [View Relations]  [View Alignment]  
Accession
PR01975
No. of Motifs
5
Creation Date
23-JUN-2009
Title
Tumour necrosis factor receptor 11B signature
Database References
PRINTS; PR01961 TNFACTORR11
MIM; 602643
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. NAKAGAWA, N., KINOSAKI, M., YAMAGUCHI, K., SHIMA, N., YASUDA, H.,
YANO, K., MORINAGA, T. AND HIGASHIO, K.
RANK is the essential signaling receptor for osteoclast differentiation 
factor in osteoclastogenesis.
BIOCHEM.BIOPHYS.RES.COMMUN. 253 395-400 (1998).
 
8. HOFBAUER, L. AND HEUFELDER, A.
Role of receptor activator of nuclear factor-kappaB ligand and 
osteoprotegerin in bone cell biology.
J.MOL.MED. 79 243-253 (2001).
 
9. WHYTE, M., OBRECHT, S., FINNEGAN, P., JONES, J., PODGORNIK, M., 
MCALISTER, W. AND MUMM, S.
Osteoprotegerin deficiency and juvenile Paget's disease. 
NEW ENG.J.MED. 347 175-184 (2002).
 
10. KIECHL, S., SCHETT, G., WENNING, G., REDLICH, K., OBERHOLLENZER, M., 
MAYR, A., SANTER, P., SMOLEN, J., POEWE, W. AND WILLEIT, J.
Osteoprotegerin is a risk factor for progressive atherosclerosis and 
cardiovascular disease.
CIRCULATION 109 2175-2180 (2004).

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 receptors 11A and 11B mediate the effects of receptor activator for
NF-kappa-B ligand (RANKL), an essential osteoclast regulatory factor. The
receptors have opposing effects - activation of TNF receptor 11A by RANKL
promotes osteoclast differentiation [7], while TNF receptor 11B acts as a
soluble decoy receptor for the ligand, thus inhibiting differentiation [8].
 
TNF receptor 11B (also known as osteoprotegerin (OPG)) is a secreted protein
that contains two death domains within its C-terminal region. Mutations in 
the TNF receptor 11B gene are associated with the autosomal recessive
osteopathy juvenile Paget disease [9]. The receptor may also be involved in
vascular calcification, and high expression levels in serum are a risk 
factor for the progression of atherosclerosis and the onset of
cardiovascular disease [10].
 
TNFACTORR11B is a 5-element fingerprint that provides a signature for
tumour necrosis factor receptor 11B. The fingerprint was derived from an 
initial alignment of 2 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those 
sections that characterise TNF receptor 11B but distinguish it from other
TNF receptor subtypes - motifs 1 and 2 reside in the N-terminal cysteine- 
rich region; motifs 3 and 4 lie partially within the first death domain; 
and motif 5 lies in the C-terminal region beyond the second death domain.
Two iterations on SPTR57_40f were required to reach convergence, at which 
point a true set comprising 8 sequences was identified.
Summary Information
8 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
588888
400000
300000
200000
12345
True Positives
A5D7R1_BOVIN  Q3UK97_MOUSE  Q4F9K2_CHICK  Q6GLN3_XENLA  
Q6PI12_MOUSE TR11B_HUMAN TR11B_MOUSE TR11B_RAT
Sequence Titles
A5D7R1_BOVIN TNFRSF11B protein - Bos taurus (Bovine).      
Q3UK97_MOUSE Putative uncharacterized protein - Mus musculus (Mouse).
Q4F9K2_CHICK OPG - Gallus gallus (Chicken).
Q6GLN3_XENLA MGC84670 protein - Xenopus laevis (African clawed frog).
Q6PI12_MOUSE Tumor necrosis factor receptor superfamily, member 11b (Osteoprotegerin) - Mus musculus (Mouse).
TR11B_HUMAN Tumor necrosis factor receptor superfamily member 11B - Homo sapiens (Human).
TR11B_MOUSE Tumor necrosis factor receptor superfamily member 11B - Mus musculus (Mouse).
TR11B_RAT Tumor necrosis factor receptor superfamily member 11B - Rattus norvegicus (Rat).
Scan History
SPTR57_40f 2  200  NSINGLE    
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
PKYLHYDPETGRQLLCDK TR11B_RAT 26 26 -
PKYLHYDEETSHQLLCDK TR11B_HUMAN 26 26 -

Motif 2 width=13
Element Seqn Id St Int Rpt
SPVCKELQTVKQE TR11B_RAT 84 40 -
SPVCKELQYVKQE TR11B_HUMAN 84 40 -

Motif 3 width=19
Element Seqn Id St Int Rpt
CGIDVTLCEEAFFRFAVPT TR11B_RAT 195 98 -
CGIDVTLCEEAFFRFAVPT TR11B_HUMAN 195 98 -

Motif 4 width=27
Element Seqn Id St Int Rpt
QLLKLWKHQNRDQEMVKKIIQDIDLCE TR11B_RAT 252 38 -
QLLKLWKHQNKDQDIVKKIIQDIDLCE TR11B_HUMAN 252 38 -

Motif 5 width=27
Element Seqn Id St Int Rpt
FTMYRLYQKLFLEMIGNQVQSVKISCL TR11B_RAT 375 96 -
FTMYKLYQKLFLEMIGNQVQSVKISCL TR11B_HUMAN 375 96 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
PKYLHYDPETGHQLLCDK Q3UK97_MOUSE 26 26 -
PKYLHYDPETGHQLLCDK TR11B_MOUSE 26 26 -
PKYLHYDPETGHQLLCDK Q6PI12_MOUSE 26 26 -
PKYLHYDPETGRQLLCDK TR11B_RAT 26 26 -
PKYLHYDEETSHQLLCDK TR11B_HUMAN 26 26 -
PKYLHYDPESSRQLMCDK A5D7R1_BOVIN 26 26 -
PKYLHYDPGTSRQVMCNQ Q4F9K2_CHICK 26 26 -
QKYSHYDPRTSMYLQCDH Q6GLN3_XENLA 25 25 -

Motif 2 width=13
Element Seqn Id St Int Rpt
SPVCKELQSVKQE Q3UK97_MOUSE 84 40 -
SPVCKELQSVKQE TR11B_MOUSE 84 40 -
SPVCKELQSVKQE Q6PI12_MOUSE 84 40 -
SPVCKELQTVKQE TR11B_RAT 84 40 -
SPVCKELQYVKQE TR11B_HUMAN 84 40 -
SPVCKELQYVKQE A5D7R1_BOVIN 84 40 -
SAVCKELQYIKQE Q4F9K2_CHICK 84 40 -
NVVCKELQYVKQQ Q6GLN3_XENLA 83 40 -

Motif 3 width=19
Element Seqn Id St Int Rpt
CGIDVTLCEEAFFRFAVPT Q3UK97_MOUSE 195 98 -
CGIDVTLCEEAFFRFAVPT TR11B_MOUSE 195 98 -
CGIDVTLCEEAFFRFAVPT Q6PI12_MOUSE 195 98 -
CGIDVTLCEEAFFRFAVPT TR11B_RAT 195 98 -
CGIDVTLCEEAFFRFAVPT TR11B_HUMAN 195 98 -
CGIDMTLCEEAFFRFAVPT A5D7R1_BOVIN 196 99 -
CGIDITLREEAMFRFAVPT Q4F9K2_CHICK 196 99 -
CEIDITLCQEAFFRFVPNN Q6GLN3_XENLA 191 95 -

Motif 4 width=27
Element Seqn Id St Int Rpt
QLLKLWKHQNRDQEMVKKIIQDIDLCE Q3UK97_MOUSE 252 38 -
QLLKLWKHQNRDQEMVKKIIQDIDLCE TR11B_MOUSE 252 38 -
QLLKLWKHQNRDQEMVKKIIQDIDLCE Q6PI12_MOUSE 252 38 -
QLLKLWKHQNRDQEMVKKIIQDIDLCE TR11B_RAT 252 38 -
QLLKLWKHQNKDQDIVKKIIQDIDLCE TR11B_HUMAN 252 38 -
QLLKLWKHQNKDQDMVKKIIQDIDLCE A5D7R1_BOVIN 253 38 -
QLLKLWKQQNKEQDMVKKIIQDIDHCE Q4F9K2_CHICK 253 38 -
HLFKLWKDHNRESESGKHLFQDLQVCE Q6GLN3_XENLA 243 33 -

Motif 5 width=27
Element Seqn Id St Int Rpt
FTMYRLYQKLFLEMIGNQVQSVKISCL Q3UK97_MOUSE 375 96 -
FTMYRLYQKLFLEMIGNQVQSVKISCL TR11B_MOUSE 375 96 -
FTMYRLYQKLFLEMIGNQVQSVKISCL Q6PI12_MOUSE 375 96 -
FTMYRLYQKLFLEMIGNQVQSVKISCL TR11B_RAT 375 96 -
FTMYKLYQKLFLEMIGNQVQSVKISCL TR11B_HUMAN 375 96 -
FTMYRLYRKLFLEMIGNQVQSLKISCL A5D7R1_BOVIN 376 96 -
FAMYRLYQKLFLEMVGSQLKSVKVRCV Q4F9K2_CHICK 376 96 -
DEMYRLYQKLLLEIFGSQTQPAKVDFK Q6GLN3_XENLA 361 91 -