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PR01974

Identifier
TNFACTORR11A  [View Relations]  [View Alignment]  
Accession
PR01974
No. of Motifs
5
Creation Date
23-JUN-2009
Title
Tumour necrosis factor receptor 11A signature
Database References
PRINTS; PR01961 TNFACTORR11
MIM; 603499
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. ZHANG, S., LIU, C., HUANG, P., ZHOU, S., REN, J., KITAMURA, Y., TANG, P.,
BI, Z. AND GAO, B.
The affinity of human RANK binding to its ligand RANKL.
ARCH.BIOCHEM.BIOPHYS. 487 49-53 (2009).

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].
 
Mutations in the TNF receptor 11A gene have been implicated in a range of 
bone disorders, such as expansile osteolysis, osteopetrosis, and Paget 
disease of bone. The receptor also has a role in immune function, vascular 
disease and mammary gland development [9].
 
TNFACTORR11A is a 5-element fingerprint that provides a signature for
tumour necrosis factor receptor 11A. 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 11A but distinguish it from other 
TNF receptor subtypes - motif 1 resides within the extracellular N-terminal
region; motif 2 lies partially within the extracellular N-terminal region
and partially within the transmembrane domain; and motifs 3 and 4 reside
within the intracellular C-terminal region. A single iteration on SPTR57_40f
was required to reach convergence, no further sequences being identified 
beyond the starting set.
Summary Information
2 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
522222
400000
300000
200000
12345
True Positives
TNR11_HUMAN   TNR11_MOUSE   
Sequence Titles
TNR11_HUMAN Tumor necrosis factor receptor superfamily member 11A - Homo sapiens (Human). 
TNR11_MOUSE Tumor necrosis factor receptor superfamily member 11A - Mus musculus (Mouse).
Scan History
SPTR57_40f 1  300  NSINGLE    
Initial Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
RLQVALQIAPPCTSEKHYEHLGRC TNR11_HUMAN 23 23 -
PLQVTLQVTPPCTQERHYEHLGRC TNR11_MOUSE 24 24 -

Motif 2 width=12
Element Seqn Id St Int Rpt
PNEPHVYLPGLI TNR11_HUMAN 204 157 -
PKEAQAYLPSLI TNR11_MOUSE 205 157 -

Motif 3 width=26
Element Seqn Id St Int Rpt
TANLWHWINEACGRLSGDKESSGDSC TNR11_HUMAN 243 27 -
TANLWNWVNDACSSLSGNKESSGDRC TNR11_MOUSE 244 27 -

Motif 4 width=22
Element Seqn Id St Int Rpt
EYMDRPSQPTDQLLFLTEPGSK TNR11_HUMAN 348 79 -
EYTDRPSQPSTGSLLLIQQGSK TNR11_MOUSE 344 74 -

Motif 5 width=16
Element Seqn Id St Int Rpt
ETLARRDSFAGNGPRF TNR11_HUMAN 573 203 -
ETLAHRDSFAGTAPRF TNR11_MOUSE 564 198 -
Final Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
RLQVALQIAPPCTSEKHYEHLGRC TNR11_HUMAN 23 23 -
PLQVTLQVTPPCTQERHYEHLGRC TNR11_MOUSE 24 24 -

Motif 2 width=12
Element Seqn Id St Int Rpt
PNEPHVYLPGLI TNR11_HUMAN 204 157 -
PKEAQAYLPSLI TNR11_MOUSE 205 157 -

Motif 3 width=26
Element Seqn Id St Int Rpt
TANLWHWINEACGRLSGDKESSGDSC TNR11_HUMAN 243 27 -
TANLWNWVNDACSSLSGNKESSGDRC TNR11_MOUSE 244 27 -

Motif 4 width=22
Element Seqn Id St Int Rpt
EYMDRPSQPTDQLLFLTEPGSK TNR11_HUMAN 348 79 -
EYTDRPSQPSTGSLLLIQQGSK TNR11_MOUSE 344 74 -

Motif 5 width=16
Element Seqn Id St Int Rpt
ETLARRDSFAGNGPRF TNR11_HUMAN 573 203 -
ETLAHRDSFAGTAPRF TNR11_MOUSE 564 198 -