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PR01918

Identifier
TNFACTORR1A  [View Relations]  [View Alignment]  
Accession
PR01918
No. of Motifs
4
Creation Date
28-APR-2008
Title
Tumour necrosis factor receptor 1A signature
Database References

PDB; 1EXT; 1FT4; 1ICH; 1NCF; 1TNR
SCOP; 1EXT; 1FT4; 1ICH; 1NCF; 1TNR
CATH; 1EXT; 1FT4; 1ICH; 1NCF; 1TNR
MIM; 191190
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. MICHEAU, O. AND TSCHOPP, J.
Induction of TNF receptor I-mediated apoptosis via two sequential signaling
complexes.
CELL 114 181-190 (2003).

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 1A (also known as TNF-R1 and CD120a antigen) contains a death 
domain within its C-terminal region that mediates interactions with several
proteins involved in signalling the downstream effects of TNF. Activation of
the receptor may induce either cell survival or apoptosis, the latter 
proceeding via recruitment of the adaptor protein FADD and caspase-8 to the
receptor complex [7]. Defects in TNF receptor 1A are the cause of familial 
hibernian fever (FHF) - an autosomal dominant disease characterised by 
recurrent fever, abdominal pain, localised tender skin lesions and myalgia.
 
TNFACTORR1A is a 4-element fingerprint that provides a signature for tumour
necrosis factor receptor 1A. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length, focusing on those sections
that characterise TNF receptor 1A but distinguish it from other TNF receptor
subtypes - motifs 1-3 reside within the extracellular N-terminal region,
each encompassing a short region of beta strand; and motif 4 lies within the
death domain in the intracellular C-terminal portion of the alignment. Two 
iterations on SPTR55_38f were required to reach convergence, at which point
a true set comprising 10 sequences was identified.
Summary Information
10 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
410101010
30000
20000
1234
True Positives
A8K4X3_HUMAN  Q2PFV5_MACFA  Q3TVS9_MOUSE  Q3U479_MOUSE  
Q95ND3_FELCA TNR1A_BOVIN TNR1A_HUMAN TNR1A_MOUSE
TNR1A_PIG TNR1A_RAT
Sequence Titles
A8K4X3_HUMAN cDNA FLJ78443, highly similar to Homo sapiens tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), mRNA - Homo sapiens (Human). 
Q2PFV5_MACFA Putative uncharacterized protein - Macaca fascicularis (Crab eating macaque) (Cynomolgus monkey).
Q3TVS9_MOUSE Osteoclast-like cell cDNA, RIKEN full-length enriched library, clone:I420042M08 product:tumor necrosis factor receptor superfamily, member 1a, full insert sequence - Mus musculus (Mouse).
Q3U479_MOUSE NOD-derived CD11c +ve dendritic cells cDNA, RIKEN full-length enriched library, clone:F630026F11 product:tumor necrosis factor receptor superfamily, member 1a, full insert sequence - Mus musculus (Mouse).
Q95ND3_FELCA Tumor necrosis factor type I - Felis silvestris catus (Cat).
TNR1A_BOVIN Tumor necrosis factor receptor superfamily member 1A precursor (p60) (TNF-R1) (TNF-RI) (TNFR-I) (p55) - Bos taurus (Bovine).
TNR1A_HUMAN Tumor necrosis factor receptor superfamily member 1A precursor (p60) (TNF-R1) (TNF-RI) (TNFR-I) (p55) (CD120a antigen) [Contains: Tumor necrosis factor receptor superfamily member 1A, membrane form; Tumor necrosis factor-binding protein 1 (TBPI)] - Homo sapiens (Human).
TNR1A_MOUSE Tumor necrosis factor receptor superfamily member 1A precursor (p60) (TNF-R1) (TNF-RI) (TNFR-I) (p55) - Mus musculus (Mouse).
TNR1A_PIG Tumor necrosis factor receptor superfamily member 1A precursor (p60) (TNF-R1) (TNF-RI) (TNFR-I) (p55) - Sus scrofa (Pig).
TNR1A_RAT Tumor necrosis factor receptor superfamily member 1A precursor (p60) (TNF-R1) (TNF-RI) (TNFR-I) (p55) - Rattus norvegicus (Rat).
Scan History
SPTR55_38f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=28
Element Seqn Id St Int Rpt
VYPAGVHGLVLHPGDREKRESLCPQGKY TNR1A_PIG 22 22 -
IYPSGVIGLVPHLGDREKRDSVCPQGKY TNR1A_HUMAN 22 22 -
VYPAGVQGLVPHPGDLEKRESPCPQGKY TNR1A_BOVIN 22 22 -

Motif 2 width=17
Element Seqn Id St Int Rpt
YRKYWSETLFQCLNCSL TNR1A_PIG 132 82 -
YRHYWSENLFQCFNCSL TNR1A_HUMAN 132 82 -
YREYWGETGFRCLNCSL TNR1A_BOVIN 132 82 -

Motif 3 width=14
Element Seqn Id St Int Rpt
FLRDKECVSCVNCK TNR1A_PIG 173 24 -
FLRENECVSCSNCK TNR1A_HUMAN 173 24 -
FLKGAKCISCHDCK TNR1A_BOVIN 173 24 -

Motif 4 width=26
Element Seqn Id St Int Rpt
RLGLSEHEIERLELQNGRCLREAQYS TNR1A_PIG 383 196 -
RLGLSDHEIDRLELQNGRCLREAQYS TNR1A_HUMAN 377 190 -
RLGLSEHEIERLELENGRHLREAQYS TNR1A_BOVIN 393 206 -
Final Motifs
Motif 1  width=28
Element Seqn Id St Int Rpt
VYPAGVHGLVLHPGDREKRESLCPQGKY TNR1A_PIG 22 22 -
IYPSGVIGLVPHLGDREKRDSVCPQGKY TNR1A_HUMAN 22 22 -
IYPSGVIGLVPHLGDREKRDSVCPQGKY A8K4X3_HUMAN 22 22 -
VYPAGVQGLVPHPGDLEKRESPCPQGKY TNR1A_BOVIN 22 22 -
IYPSGVIGLVPPLRDREKRDSVCPQGKY Q2PFV5_MACFA 22 22 -
IYPLRVTGLVPHLRDREKRAIPCPQGKY Q95ND3_FELCA 22 22 -
IHPSGVTGLVPSLGDREKRDSLCPQGKY Q3TVS9_MOUSE 22 22 -
IHPSGVTGLVPSLGDREKRDSLCPQGKY TNR1A_MOUSE 22 22 -
IHPSGVTGLVPSLGDREKRDSLCPQGKY Q3U479_MOUSE 22 22 -
IHPSGVTGLVPSLGDREKRDNLCPQGKY TNR1A_RAT 22 22 -

Motif 2 width=17
Element Seqn Id St Int Rpt
YRKYWSETLFQCLNCSL TNR1A_PIG 132 82 -
YRHYWSENLFQCFNCSL TNR1A_HUMAN 132 82 -
YRHYWSENLFQCFNCSL A8K4X3_HUMAN 132 82 -
YREYWGETGFRCLNCSL TNR1A_BOVIN 132 82 -
YRYYWSENLFQCFNCSL Q2PFV5_MACFA 132 82 -
YRYYWSETHFQCLNCSL Q95ND3_FELCA 132 82 -
FQRYLSETHFQCVDCSP Q3TVS9_MOUSE 132 82 -
FQRYLSETHFQCVDCSP TNR1A_MOUSE 132 82 -
FQRYLSETHFQCVDCSP Q3U479_MOUSE 132 82 -
FQRYLSETHFQCVDCSP TNR1A_RAT 132 82 -

Motif 3 width=14
Element Seqn Id St Int Rpt
FLRDKECVSCVNCK TNR1A_PIG 173 24 -
FLRENECVSCSNCK TNR1A_HUMAN 173 24 -
FLRENECVSCSNCK A8K4X3_HUMAN 173 24 -
FLKGAKCISCHDCK TNR1A_BOVIN 173 24 -
FLRENECVSCSNCK Q2PFV5_MACFA 173 24 -
FLRGNECVSCVNCK Q95ND3_FELCA 173 24 -
FLRESECVLCSHCK Q3TVS9_MOUSE 173 24 -
FLRESECVPCSHCK TNR1A_MOUSE 173 24 -
FLRESECVPCSHCK Q3U479_MOUSE 173 24 -
FLSGNECTPCSHCK TNR1A_RAT 173 24 -

Motif 4 width=26
Element Seqn Id St Int Rpt
RLGLSEHEIERLELQNGRCLREAQYS TNR1A_PIG 383 196 -
RLGLSDHEIDRLELQNGRCLREAQYS TNR1A_HUMAN 377 190 -
RLGLSDHEIDRLELQNGLCLREAQYS A8K4X3_HUMAN 377 190 -
RLGLSEHEIERLELENGRHLREAQYS TNR1A_BOVIN 393 206 -
RLGLSDHEIDRLELQNGRCLREAQYS Q2PFV5_MACFA 377 190 -
RLGLSEHEIERLELQNGRCLREAHYS Q95ND3_FELCA 368 181 -
FMGLSEHEIERLEMQNGRCLREAQYS Q3TVS9_MOUSE 377 190 -
FMGLSEHEIERLEMQNGRCLREAQYS TNR1A_MOUSE 377 190 -
FMGLSEHEIERLEMQNGRCLREAQYS Q3U479_MOUSE 377 190 -
LLGLSEHEIERLELQNGRCLREAHYS TNR1A_RAT 384 197 -