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PR01237

Identifier
TNFC  [View Relations]  [View Alignment]  
Accession
PR01237
No. of Motifs
8
Creation Date
20-OCT-1999
Title
Tumour necrosis factor c (lymphotoxin-beta) signature
Database References
PRINTS; PR01234 TNECROSISFCT
INTERPRO; IPR002961
Literature References
1. FRANSEN, L., MULLER, R., MARMENOUT, A., TAVERNIER, J., VAN DER
HEYDEN, J., KAWASHIMA, E., CHOLLET, A., TIZARD, R., VAN HEUVERSWYN, H.
AND VAN VLIET, A.
Molecular cloning of mouse tumour necrosis factor cDNA and its eukaryotic
expression.
NUCLEIC ACIDS RES. 13 4417-4429 (1985).
 
2. KRIEGLER, M., PEREZ, C., DEFAY, K., ALBERT, I. AND LU, S.D. 
A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane
protein: ramifications for the complex physiology of TNF.
CELL 53 45-53 (1988). 
 
3. SHERRY, B., JUE, D.M., ZENTELLA, A. AND CERAMI, A.
Characterization of high molecular weight glycosylated forms of murine 
tumor necrosis factor.
BIOCHEM.BIOPHYS.RES.COMMUN. 173 1072-1078 (1990). 
 
4. CSEH, K. AND BEUTLER, B.
Alternative cleavage of the cachectin/tumor necrosis factor propeptide 
results in a larger, inactive form of secreted protein.
J.BIOL.CHEM. 264 16256-16260 (1989). 
 
5. BROWNING, J.L., NGAM-EK, A., LAWTON, P., DEMARINIS, J., TIZARD, R.,
CHOW, E.P., HESSION, C., O'BRINE-GRECO, B., FOLEY, S.F. AND WARE, C.F.
Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric
complex with lymphotoxin on the cell surface.
CELL 72 847-856 (1993). 

Documentation
Tumor necrosis factor (TNF) (or cachectin) is a monocyte-derived cytotoxin
that has been implicated in tumour regression, septic shock and cachexia
[1,2]. The protein is synthesised as a prohormone with an unusually long 
and atypical signal sequence, which is absent from the mature secreted
cytokine [3]. A short hydrophobic stretch of amino acids serves to anchor 
the prohormone in lipid bilayers [4]. Both the mature protein and a 
partially-processed form of the hormone are secreted after cleavage of the
propeptide [4]. 
 
Lymphotoxin-alpha (LT-alpha or TNF-beta) and lymphotoxin-beta (LT-beta) are
related cytokines produced by lymphocytes. The proteins are cytotoxic for a
wide range of tumour cells in vitro and in vivo. The gene for LT-beta is
found next to the TNF-LT locus in the major histocompatibility complex (MHC),
a region of the MHC with possible linkage to autoimmune disease [5]. It is
possible that a surface LT-alpha/LT-beta complex may have a specific role
in immune regulation distinct from the functions ascribed to TNF [5]. 
 
TNFC is an 8-element fingerprint that provides a signature for tumour 
necrosis factor C (LT-beta). 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-C but distinguish it from the rest of the TNF family -
motif 2 spans the putative signal-anchor. A single iteration on SPTR37_10f
was required to reach convergence, no further sequences being identified 
beyond the starting set. A single partial match was found, P78370, a human
lymphotoxin-beta isoform variant that matches motifs 1 and 2.
Summary Information
   2 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
822222222
700000000
600000000
500000000
400000000
300000000
211000000
12345678
True Positives
TNFC_HUMAN    TNFC_MOUSE    
True Positive Partials
Codes involving 2 elements
P78370
Sequence Titles
TNFC_HUMAN  LYMPHOTOXIN-BETA (LT-BETA) (TUMOR NECROSIS FACTOR C) - HOMO SAPIENS (HUMAN). 
TNFC_MOUSE LYMPHOTOXIN-BETA (LT-BETA) (TUMOR NECROSIS FACTOR C) - MUS MUSCULUS (MOUSE).

P78370 LYMPHOTOXIN BETA ISOFORM VARIANT - HOMO SAPIENS (HUMAN).
Scan History
SPTR37_10f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
GALGLEGRGGRLQGRGSLLLAVAG TNFC_HUMAN 2 2 -
GTRGLQGLGGRPQGRGCLLLAVAG TNFC_MOUSE 2 2 -

Motif 2 width=22
Element Seqn Id St Int Rpt
TLLLAVPITVLAVLALVPQDQG TNFC_HUMAN 31 5 -
TLLLAVPITVLAVLALVPQDQG TNFC_MOUSE 31 5 -

Motif 3 width=20
Element Seqn Id St Int Rpt
GFQKLPEEEPETDLSPGLPA TNFC_HUMAN 70 17 -
GVQQLPKGEPETDLNPELPA TNFC_MOUSE 136 83 -

Motif 4 width=12
Element Seqn Id St Int Rpt
GTQFSDAEGLAL TNFC_HUMAN 116 26 -
GAQFSPTHGLAL TNFC_MOUSE 182 26 -

Motif 5 width=23
Element Seqn Id St Int Rpt
GDPQGRSVTLRSSLYRAGGAYGP TNFC_HUMAN 150 22 -
GRSRARSLTLRSALYRAGGAYGR TNFC_MOUSE 215 21 -

Motif 6 width=19
Element Seqn Id St Int Rpt
GTPELLLEGAETVTPVLDP TNFC_HUMAN 173 0 -
GSPELLLEGAETVTPVVDP TNFC_MOUSE 238 0 -

Motif 7 width=21
Element Seqn Id St Int Rpt
GYGPLWYTSVGFGGLVQLRRG TNFC_HUMAN 196 4 -
GYGSLWYTSVGFGGLAQLRSG TNFC_MOUSE 258 1 -

Motif 8 width=21
Element Seqn Id St Int Rpt
ERVYVNISHPDMVDFARGKTF TNFC_HUMAN 217 0 -
ERVYVNISHPDMVDYRRGKTF TNFC_MOUSE 279 0 -
Final Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
GALGLEGRGGRLQGRGSLLLAVAG TNFC_HUMAN 2 2 -
GTRGLQGLGGRPQGRGCLLLAVAG TNFC_MOUSE 2 2 -

Motif 2 width=22
Element Seqn Id St Int Rpt
TLLLAVPITVLAVLALVPQDQG TNFC_HUMAN 31 5 -
TLLLAVPITVLAVLALVPQDQG TNFC_MOUSE 31 5 -

Motif 3 width=20
Element Seqn Id St Int Rpt
GFQKLPEEEPETDLSPGLPA TNFC_HUMAN 70 17 -
GVQQLPKGEPETDLNPELPA TNFC_MOUSE 136 83 -

Motif 4 width=12
Element Seqn Id St Int Rpt
GTQFSDAEGLAL TNFC_HUMAN 116 26 -
GAQFSPTHGLAL TNFC_MOUSE 182 26 -

Motif 5 width=23
Element Seqn Id St Int Rpt
GDPQGRSVTLRSSLYRAGGAYGP TNFC_HUMAN 150 22 -
GRSRARSLTLRSALYRAGGAYGR TNFC_MOUSE 215 21 -

Motif 6 width=19
Element Seqn Id St Int Rpt
GTPELLLEGAETVTPVLDP TNFC_HUMAN 173 0 -
GSPELLLEGAETVTPVVDP TNFC_MOUSE 238 0 -

Motif 7 width=21
Element Seqn Id St Int Rpt
GYGPLWYTSVGFGGLVQLRRG TNFC_HUMAN 196 4 -
GYGSLWYTSVGFGGLAQLRSG TNFC_MOUSE 258 1 -

Motif 8 width=21
Element Seqn Id St Int Rpt
ERVYVNISHPDMVDFARGKTF TNFC_HUMAN 217 0 -
ERVYVNISHPDMVDYRRGKTF TNFC_MOUSE 279 0 -