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PR01971

Identifier
TNFACTORR21  [View Relations]  [View Alignment]  
Accession
PR01971
No. of Motifs
4
Creation Date
24-JUN-2009
Title
Tumour necrosis factor receptor 21 signature
Database References

PDB; 2DBH
CATH; 2DBH
MIM; 605732
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. BENSCHOP, R., WEI, T. AND NA, S.
Tumor Necrosis Factor Receptor Superfamily Member 21: TNFR-Related Death 
Receptor-6, DR6.
ADV.EXP.MED.BIOL. 647 186-194 (2009).
 
8. NIKOLAEV, A., MCLAUGHLIN, T., O'LEARY, D. AND TESSIER-LAVIGNE, M.
APP binds DR6 to trigger axon pruning and neuron death via distinct 
caspases.
NATURE 457 981-989 (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 receptor 21, also termed death receptor 6 (DR6), is expressed 
ubiquitously, with high expression in lymphoid organs, heart, brain and 
pancreas. The receptor plays an important regulatory role in the generation
of adaptive immunity and may be involved in tumour cell survival and immune
evasion [7]. It has also been implicated in the pathogenesis of Alzheimer's
disease, as activation of the receptor by beta-amyloid precursor protein
triggers neuronal death via a caspase-dependent pathway [8].
 
TNFACTORR21 is a 4-element fingerprint that provides a signature for tumour
necrosis factor receptor 21. The fingerprint was derived from an initial
alignment of 5 sequences: the motifs were drawn from conserved regions in 
the C-terminal half of the alignment, focusing on those sections that
characterise TNF receptor 21 but distinguish it from other TNF receptor
subtypes - motif 1 spans part of the extracellular N-terminal region and 
part of the transmembrane domain, and motifs 2-4 lie in the intracellular
C-terminal region. Two iterations on SPTR57_40f were required to reach
convergence, at which point a true set comprising 11 sequences was
identified. 
Summary Information
11 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
411111111
30000
20000
1234
True Positives
A5D8S6_DANRE  B3KMB6_HUMAN  Q08DN1_BOVIN  Q0IHT5_XENTR  
Q3UYG3_MOUSE Q543Y9_MOUSE Q5TYN2_DANRE Q8BZU6_MOUSE
Q98SM6_CHICK TNR21_HUMAN TNR21_MOUSE
Sequence Titles
A5D8S6_DANRE Tnfrsf21 protein - Danio rerio (Zebrafish) (Brachydanio rerio). 
B3KMB6_HUMAN cDNA FLJ10642 fis, clone NT2RP2005752, highly similar to Tumor necrosis factor receptor superfamily member 21 - Homo sapiens (Human).
Q08DN1_BOVIN Tumor necrosis factor receptor superfamily, member 21 - Bos taurus (Bovine).
Q0IHT5_XENTR Tumor necrosis factor receptor superfamily, member 21 - Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
Q3UYG3_MOUSE Putative uncharacterized protein - Mus musculus (Mouse).
Q543Y9_MOUSE Putative uncharacterized protein - Mus musculus (Mouse).
Q5TYN2_DANRE Death receptor 6 - Danio rerio (Zebrafish) (Brachydanio rerio).
Q8BZU6_MOUSE Putative uncharacterized protein - Mus musculus (Mouse).
Q98SM6_CHICK Death receptor 6 - Gallus gallus (Chicken).
TNR21_HUMAN Tumor necrosis factor receptor superfamily member 21 - Homo sapiens (Human).
TNR21_MOUSE Tumor necrosis factor receptor superfamily member 21 - Mus musculus (Mouse).
Scan History
SPTR57_40f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
AHKHFDINEHLPW TNR21_MOUSE 340 340 -
LHKHFDINEHLPW TNR21_HUMAN 340 340 -
VHQHFDINEHLPW Q98SM6_CHICK 321 321 -
NANDFDINEHLPW Q0IHT5_XENTR 297 297 -
SHKHFDINEHLPW Q5TYN2_DANRE 327 327 -

Motif 2 width=20
Element Seqn Id St Int Rpt
PRQDPSAIVEKAGLKKSLTP TNR21_MOUSE 381 28 -
PRQDPSAIVEKAGLKKSMTP TNR21_HUMAN 381 28 -
PRQDPSAIVEKAIMKKSTTP Q98SM6_CHICK 362 28 -
PKQDPSSIVEKAGFKKSNTL Q0IHT5_XENTR 338 28 -
PRQDPSSIMEKAIHKKPSSP Q5TYN2_DANRE 368 28 -

Motif 3 width=18
Element Seqn Id St Int Rpt
NREKWIYYRNGHGIDILK TNR21_MOUSE 403 2 -
NREKWIYYCNGHGIDILK TNR21_HUMAN 403 2 -
NREKWIYYCNGHGIDILK Q98SM6_CHICK 384 2 -
NREKWVYYCNGHGIDILK Q0IHT5_XENTR 360 2 -
TKERWIYYSNGQGVDILK Q5TYN2_DANRE 390 2 -

Motif 4 width=25
Element Seqn Id St Int Rpt
QVGSQWKDIYQFLCNASEREVAAFS TNR21_MOUSE 425 4 -
QVGSQWKDIYQFLCNASEREVAAFS TNR21_HUMAN 425 4 -
QVGSQWKDIYQFLCNASEREVAAFS Q98SM6_CHICK 406 4 -
QIGSQWQDIYQFLCNANEHEVAAFS Q0IHT5_XENTR 382 4 -
QIGSQWIDLYKSLASATEREVAAFS Q5TYN2_DANRE 412 4 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
AHKHFDINEHLPW Q3UYG3_MOUSE 340 340 -
AHKHFDINEHLPW TNR21_MOUSE 340 340 -
AHKHFDINEHLPW Q8BZU6_MOUSE 258 258 -
AHKHFDINEHLPW Q543Y9_MOUSE 340 340 -
LHKHFDINEHLPW B3KMB6_HUMAN 340 340 -
LHKHFDINEHLPW TNR21_HUMAN 340 340 -
PHKHFDINEHLPW Q08DN1_BOVIN 337 337 -
VHQHFDINEHLPW Q98SM6_CHICK 321 321 -
NANDFDINEHLPW Q0IHT5_XENTR 297 297 -
SHKHFDINEHLPW A5D8S6_DANRE 327 327 -
SHKHFDINEHLPW Q5TYN2_DANRE 327 327 -

Motif 2 width=20
Element Seqn Id St Int Rpt
PRQDPSAIVEKAGLKKSLTP Q3UYG3_MOUSE 381 28 -
PRQDPSAIVEKAGLKKSLTP TNR21_MOUSE 381 28 -
PRQDPSAIVEKAGLKKSLTP Q8BZU6_MOUSE 299 28 -
PRQDPSAIVEKAGLKKSLTP Q543Y9_MOUSE 381 28 -
PRQDPSAIVEKAGLKKSMTP B3KMB6_HUMAN 381 28 -
PRQDPSAIVEKAGLKKSMTP TNR21_HUMAN 381 28 -
PRQDPSAIVEKAGLKKSMAP Q08DN1_BOVIN 378 28 -
PRQDPSAIVEKAIMKKSTTP Q98SM6_CHICK 362 28 -
PKQDPSSIVEKAGFKKSNTL Q0IHT5_XENTR 338 28 -
PRQDPSSIMEKAIHKKPSSP A5D8S6_DANRE 368 28 -
PRQDPSSIMEKAIHKKPSSP Q5TYN2_DANRE 368 28 -

Motif 3 width=18
Element Seqn Id St Int Rpt
NREKWIYYRNGHGIDILK Q3UYG3_MOUSE 403 2 -
NREKWIYYRNGHGIDILK TNR21_MOUSE 403 2 -
NREKWIYYRNGHGIDILK Q8BZU6_MOUSE 321 2 -
NREKWIYYRNGHGIDILK Q543Y9_MOUSE 403 2 -
NREKWIYYCNGHGIDILK B3KMB6_HUMAN 403 2 -
NREKWIYYCNGHGIDILK TNR21_HUMAN 403 2 -
NREKWIYYCNGHGIDILK Q08DN1_BOVIN 400 2 -
NREKWIYYCNGHGIDILK Q98SM6_CHICK 384 2 -
NREKWVYYCNGHGIDILK Q0IHT5_XENTR 360 2 -
TKERWIYYSNGQGVDILK A5D8S6_DANRE 390 2 -
TKERWIYYSNGQGVDILK Q5TYN2_DANRE 390 2 -

Motif 4 width=25
Element Seqn Id St Int Rpt
QVGSQWKDIYQFLCNASEREVAAFS Q3UYG3_MOUSE 425 4 -
QVGSQWKDIYQFLCNASEREVAAFS TNR21_MOUSE 425 4 -
QVGSQWKDIYQFLCNASEREVAAFS Q8BZU6_MOUSE 343 4 -
QVGSQWKDIYQFLCNASEREVAAFS Q543Y9_MOUSE 425 4 -
QVGSQWKDIYQFLCNASEREVAAFS B3KMB6_HUMAN 425 4 -
QVGSQWKDIYQFLCNASEREVAAFS TNR21_HUMAN 425 4 -
QVGSQWKDIYQFLCNASEREVAAFS Q08DN1_BOVIN 422 4 -
QVGSQWKDIYQFLCNASEREVAAFS Q98SM6_CHICK 406 4 -
QIGSQWQDIYQFLCNANEHEVAAFS Q0IHT5_XENTR 382 4 -
QIGSQWIDLYKSLASATEREVAAFS A5D8S6_DANRE 412 4 -
QIGSQWIDLYKSLASATEREVAAFS Q5TYN2_DANRE 412 4 -