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PR01360

Identifier
INTRLEUKIN1X  [View Relations]  [View Alignment]  
Accession
PR01360
No. of Motifs
7
Creation Date
13-MAY-2000
Title
Interleukin-1 receptor antagonist precursor IL-1RA signature
Database References
PRINTS; PR00262 IL1HBGF; PR00264 INTERLEUKIN1
PDB; 1IRA
SCOP; 1IRA
CATH; 1IRA
Literature References
1. OPPENHEIM, J.J., KOVACS, E.J., MATSUSHIMA, K. AND DURUM, S.K. 
There is more than one interleukin 1. 
IMMUNOL.TODAY 7 45-56 (1986).
 
2. ROTHWELL, N.J. AND LUHESHI, G.N.
Interleukin-1 in the brain: biology, pathology and therapeutic target.
TRENDS NEUROSCIENCE 23(12) 618-625 (2000).
 
3. EISENBERG, S.P., BREWER, M.T., VERDERBER, E., HEIMDAL, P., BRANDHUBER,
B.J. AND THOMPSON, R.C. 
Interleukin 1 receptor antagonist is a member of the interleukin 1 gene 
family: Evolution of a cytokine control mechanism. 
PROC.NATL.ACAD.SCI.U.S.A. 88 5232-5236 (1991). 
 
4. PRIESTLE, J.P., SCHAR, H.-P. AND GRUTTER, M.G. 
Crystallographic refinement of interleukin 1 beta at 2.0 angstrom 
resolution. 
PROC.NATL.ACAD.SCI.U.S.A. 86 9667-9671 (1989). 
 
5. MURZIN, A.G., LESK, A.M. AND CHOTHIA, C. 
Patterns of structure and sequence in the Kunitz inhibitors, interleukins-1
beta and 1 alpha and fibroblast growth factors. 
J.MOL.BIOL. 223 531-543 (1992). 

Documentation
Interleukin-1 (IL-1) is a cytokine with a wide range of biological and
physiological effects, including fever, prostaglandin synthesis (in e.g.,
fibroblasts, muscle and endothelial cells), T-lymphocyte activation, and 
interleukin-2 production [1]. This family is a member of a superfamily that
also contains the heparin binding growth factors (HBGF), the Kunitz-type 
soybean trypsin inhibitors (STI) and histactophilin. All have very similar
structures, but although the interleukin-1 and HBGF families share some
sequence similarity (about 25%), they show none at all to the STIs.
 
Over a hundred cytokines have now been identified, including several
putative new members of the IL-1 family [2]. The IL-1 family consists of 2
main classes, designated alpha (IL1A) and beta (IL1B), as well as the more
recently discovered IL-1 receptor antagonist (IL1RA). Sequence similarity 
is high within the IL1A and IL1B subfamilies (about 60-70%) but low between
them (less than 30%). IL1As and IL1Bs are synthesised as larger precursors, 
which are processed to give mature carboxy fragments. IL1B requires this 
cleavage to become biologically active, but IL1A precursor is already 
active. Both IL1A and IL1B bind to the same IL1-specific receptor on the 
target cell, which is then internalised to initiate the relevant effects
(which appear to be similar or identical).
 
IL1RA binds to the IL1 receptor, blocking the effects of IL1A and IL1B
whilst eliciting no response of its own. From sequence comparisons it seems
to have arisen by gene duplication before IL1 diverged into IL1A and IL1B,
as it has features of both [3]. It seems likely to have the same fold as
IL1A and IL1B. 
                
The crystal structures of IL1A and IL1B [4] have been solved, showing them 
to share the same 12-stranded beta-sheet structure as both the heparin
binding growth factors and the Kunitz-type soybean trypsin inhibitors [5].
The beta-sheets are arranged in 3 similar lobes around a central axis, 6
strands forming an anti-parallel beta-barrel. Several regions, especially 
the loop between strands 4 and 5, have been implicated in receptor binding.
 
INTRLEUKIN1X is a 7-element fingerprint that provides a signature for the
interleukin-1 receptor antagonist precursor IL-1RA. The fingerprint was
derived from an initial alignment of 4 sequences: the motifs were drawn 
from conserved regions spanning the full alignment length - motif 1 encodes
strands 1 and 2; motif 2 spans strand 3, alpha-helix 1 and strand 4; motif
3 encompasses strands 5 and 6; motif 4 spans strand 7 and helix 2; motif 5
spans helix 3 and strands 8 and 9; motif 6 encompasses strands 10-12; and
motif 7 spans helix 4 and stand 13. Three iterations on SPTR37_10f were
required to reach convergence, at which point a true set comprising 9 
sequences was identified. A single partial match was also found, O73909,
an IL-1 beta from chicken that matches four motifs.
Summary Information
   9 codes involving  7 elements
0 codes involving 6 elements
0 codes involving 5 elements
1 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
79999999
60000000
50000000
41010110
30000000
20000000
1234567
True Positives
IL1X_BOVIN    IL1X_HORSE    IL1X_HUMAN    IL1X_MOUSE    
IL1X_PIG IL1X_RABIT IL1X_RAT O70207
Q14628
True Positive Partials
Codes involving 4 elements
O73909
Sequence Titles
IL1X_BOVIN  INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN PRECURSOR (IL-1RA) (IL-1RN) (IRAP) - BOS TAURUS (BOVINE). 
IL1X_HORSE INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN PRECURSOR (IL-1RA) (IL-1RN) (IRAP) - EQUUS CABALLUS (HORSE).
IL1X_HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN PRECURSOR (IL-1RA) (ICIL- 1RA) (IRAP) (IL-1RN) - HOMO SAPIENS (HUMAN).
IL1X_MOUSE INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN PRECURSOR (IL-1RA) (IL-1RN) (IRAP) - MUS MUSCULUS (MOUSE).
IL1X_PIG INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN PRECURSOR (IL-1RA) (IL-1RN) (IRAP) - SUS SCROFA (PIG).
IL1X_RABIT INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN PRECURSOR (IL-1RA) (IL-1RN) (IRAP) - ORYCTOLAGUS CUNICULUS (RABBIT).
IL1X_RAT INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN PRECURSOR (IL-1RA) (IL-1RN) (IRAP) - RATTUS NORVEGICUS (RAT).
O70207 INTRACELLULAR INTERLEUKIN-1 RECEPTOR ANTAGONIST - MUS MUSCULUS (MOUSE).
Q14628 INTRACELLULAR IL-1 RECEPTOR ANTAGONIST TYPE II - HOMO SAPIENS (HUMAN).

O73909 INTERLEUKIN-1BETA - GALLUS GALLUS (CHICKEN).
Scan History
SPTR37_10f 3  50   NSINGLE    
Initial Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
KMQAFRIWDVNQKTFYLRNNQ IL1X_HUMAN 34 34 -
KMQAFRIWDTNQKTFYLRNNQ IL1X_RAT 35 35 -
KMQAFRIWDTNQKTFYLRNNQ IL1X_MOUSE 35 35 -
RMQAFRIWDVNQKTFYLRNNQ IL1X_RABIT 34 34 -

Motif 2 width=21
Element Seqn Id St Int Rpt
LVAGYLQGPNVNLEEKIDVVP IL1X_HUMAN 55 0 -
LIAGYLQGPNTKLEEKIDMVP IL1X_RAT 56 0 -
LIAGYLQGPNIKLEEKIDMVP IL1X_MOUSE 56 0 -
LVAGYLQGPNAKLEERIDVVP IL1X_RABIT 55 0 -

Motif 3 width=18
Element Seqn Id St Int Rpt
FLGIHGGKMCLSCVKSGD IL1X_HUMAN 82 6 -
FLGIHGGKLCLSCVKSGD IL1X_RAT 83 6 -
FLGIHGGKLCLSCAKSGD IL1X_MOUSE 83 6 -
FLGIQRGKLCLSCVKSGD IL1X_RABIT 82 6 -

Motif 4 width=16
Element Seqn Id St Int Rpt
RLQLEAVNITDLSENR IL1X_HUMAN 102 2 -
KLQLEEVNITDLNKNK IL1X_RAT 103 2 -
KLQLEEVNITDLSKNK IL1X_MOUSE 103 2 -
KLHLEAVNITDLGKNK IL1X_RABIT 102 2 -

Motif 5 width=21
Element Seqn Id St Int Rpt
DKRFAFIRSDSGPTTSFESAA IL1X_HUMAN 120 2 -
DKRFTFIRSETGPTTSFESLA IL1X_RAT 121 2 -
DKRFTFIRSEKGPTTSFESAA IL1X_MOUSE 121 2 -
DKRFTFIRSNSGPTTTFESAS IL1X_RABIT 120 2 -

Motif 6 width=19
Element Seqn Id St Int Rpt
CPGWFLCTAMEADQPVSLT IL1X_HUMAN 141 0 -
CPGWFLCTTLEADHPVSLT IL1X_RAT 142 0 -
CPGWFLCTTLEADRPVSLT IL1X_MOUSE 142 0 -
CPGWFLCTALEADQPVSLT IL1X_RABIT 141 0 -

Motif 7 width=18
Element Seqn Id St Int Rpt
TNMPDEGVMVTKFYFQED IL1X_HUMAN 159 -1 -
TNTPKEPCTVTKFYFQED IL1X_RAT 160 -1 -
TNTPEEPLIVTKFYFQED IL1X_MOUSE 160 -1 -
TNTPDDSIVVTKFYFQED IL1X_RABIT 159 -1 -
Final Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
KMQAFRIWDVNQKTFYLRNNQ IL1X_HUMAN 34 34 -
KMQAFRIWDVNQKTFYLRNNQ Q14628 37 37 -
RMQAFRIWDVNQKTFYLRNNQ IL1X_PIG 34 34 -
KMQAFRIWDTNQKTFYLRNNQ IL1X_RAT 35 35 -
KMQAFRIWDTNQKTFYLRNNQ IL1X_MOUSE 35 35 -
KMQAFRIWDTNQKTFYLRNNQ O70207 16 16 -
RMQAFRIWDVNQKTFYLRNNQ IL1X_RABIT 34 34 -
EMQAFRIWDVNQKIFYLRNNQ IL1X_BOVIN 32 32 -
KMQAFRIWDVNQKTFYMRNNQ IL1X_HORSE 34 34 -

Motif 2 width=21
Element Seqn Id St Int Rpt
LVAGYLQGPNVNLEEKIDVVP IL1X_HUMAN 55 0 -
LVAGYLQGPNVNLEEKIDVVP Q14628 58 0 -
LVAGYLQGPNTKLEEKIDVVP IL1X_PIG 55 0 -
LIAGYLQGPNTKLEEKIDMVP IL1X_RAT 56 0 -
LIAGYLQGPNIKLEEKIDMVP IL1X_MOUSE 56 0 -
LIAGYLQGPNIKLEEKIDMVP O70207 37 0 -
LVAGYLQGPNAKLEERIDVVP IL1X_RABIT 55 0 -
LVAGYLQGPNTKLEEKIDVVP IL1X_BOVIN 53 0 -
LVAGYLQESNTKLQEKIDVVP IL1X_HORSE 55 0 -

Motif 3 width=18
Element Seqn Id St Int Rpt
FLGIHGGKMCLSCVKSGD IL1X_HUMAN 82 6 -
FLGIHGGKMCLSCVKSGD Q14628 85 6 -
FLGIHGGKLCLSCVKSGD IL1X_PIG 82 6 -
FLGIHGGKLCLSCVKSGD IL1X_RAT 83 6 -
FLGIHGGKLCLSCAKSGD IL1X_MOUSE 83 6 -
FLGIHGGKLCLSCAKSGD O70207 64 6 -
FLGIQRGKLCLSCVKSGD IL1X_RABIT 82 6 -
FLGIHGGKLCLACVKSGD IL1X_BOVIN 80 6 -
FLGLHGRKLCLACVKSGD IL1X_HORSE 82 6 -

Motif 4 width=16
Element Seqn Id St Int Rpt
RLQLEAVNITDLSENR IL1X_HUMAN 102 2 -
RLQLEAVNITDLSENR Q14628 105 2 -
KLQLDAVNITDLRKNS IL1X_PIG 102 2 -
KLQLEEVNITDLNKNK IL1X_RAT 103 2 -
KLQLEEVNITDLSKNK IL1X_MOUSE 103 2 -
KLQLEEVNITDLSKNK O70207 84 2 -
KLHLEAVNITDLGKNK IL1X_RABIT 102 2 -
KLKLEAVNITDLNQNR IL1X_BOVIN 100 2 -
RFQLEAVNITDLSKNK IL1X_HORSE 102 2 -

Motif 5 width=21
Element Seqn Id St Int Rpt
DKRFAFIRSDSGPTTSFESAA IL1X_HUMAN 120 2 -
DKRFAFIRSDSGPTTSFESAA Q14628 123 2 -
DKRFTFIRSDSGPTTSFESAA IL1X_PIG 120 2 -
DKRFTFIRSETGPTTSFESLA IL1X_RAT 121 2 -
DKRFTFIRSEKGPTTSFESAA IL1X_MOUSE 121 2 -
DKRFTFIRSEKGPTTSFESAA O70207 102 2 -
DKRFTFIRSNSGPTTTFESAS IL1X_RABIT 120 2 -
DKRFAFIRFDNGPTTSFESAA IL1X_BOVIN 118 2 -
NKRFTFIRSNSGPTTSFESAA IL1X_HORSE 120 2 -

Motif 6 width=19
Element Seqn Id St Int Rpt
CPGWFLCTAMEADQPVSLT IL1X_HUMAN 141 0 -
CPGWFLCTAMEADQPVSLT Q14628 144 0 -
CPGWFLCTALEADQPVGLT IL1X_PIG 141 0 -
CPGWFLCTTLEADHPVSLT IL1X_RAT 142 0 -
CPGWFLCTTLEADRPVSLT IL1X_MOUSE 142 0 -
CPGWFLCTTLEADRPVSLT O70207 123 0 -
CPGWFLCTALEADQPVSLT IL1X_RABIT 141 0 -
CPGWFLCTSLEADQPVGLT IL1X_BOVIN 139 0 -
CPGWFLCTAQEADRPVSLT IL1X_HORSE 141 0 -

Motif 7 width=18
Element Seqn Id St Int Rpt
TNMPDEGVMVTKFYFQED IL1X_HUMAN 159 -1 -
TNMPDEGVMVTKFYFQED Q14628 162 -1 -
TNTPKAAVKVTKFYFQQD IL1X_PIG 159 -1 -
TNTPKEPCTVTKFYFQED IL1X_RAT 160 -1 -
TNTPEEPLIVTKFYFQED IL1X_MOUSE 160 -1 -
TNTPEEPLIVTKFYFQED O70207 141 -1 -
TNTPDDSIVVTKFYFQED IL1X_RABIT 159 -1 -
TNMPTEALKVTKFYFQQD IL1X_BOVIN 157 -1 -
TNKPKESFMVTKFYLQED IL1X_HORSE 159 -1 -