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PR00573

Identifier
INTRLEUKN8BR  [View Relations]  [View Alignment]  
Accession
PR00573
No. of Motifs
4
Creation Date
10-SEP-1996  (UPDATE 07-JUN-1999)
Title
Interleukin 8B receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00427 INTRLEUKIN8R
INTERPRO; IPR000057
GCRDB; GCR_0077; GCR_0610; GCR_1001; GCR_0861; GCR_0913; GCR_0550

GCRDB; GCR_0838
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994).
 
2. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
G protein-coupled receptor fingerprints.
7TM, VOLUME 2, EDS. G.VRIEND AND B.BYWATER (1993).
 
3. BIRNBAUMER, L.
G proteins in signal transduction.
ANNU.REV.PHARMACOL.TOXICOL. 30 675-705 (1990).
 
4. CASEY, P.J. AND GILMAN, A.G.
G protein involvement in receptor-effector coupling.
J.BIOL.CHEM. 263(6) 2577-2580 (1988).
 
5. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Design of a discriminating fingerprint for G protein-coupled receptors.
PROTEIN ENG. 6(2) 167-176 (1993).
 
6. HOLMES, W.E., LEE, J., KUANG, W-J., RICE, G.C. AND WOOD, W.I.
Structure and functional expression of a human interleukin-8 receptor.
SCIENCE 253 1278-1280 (1991).
 
7. MOLLEREAU, C., MUSCATELLI, F., MATTEI, M.G., VASSART, G. AND 
PARMENTIER, M.
The high-affinity interleukin 8 receptor gene (IL8RA) maps to the 2q33-q36
region of the human genome: cloning of a pseudogene (IL8RBP) for the
low-affinity receptor.
GENOMICS 16 248-251 (1993).
 
8. BAGGIOLINI, M. AND CLARK-LEWIS, I.
Interleukin-8, a chemotactic and inflammatory cytokine.
FEBS LETT. 307 97-101 (1992).
 
9. WATSON, S. AND ARKINSTALL, S.
Chemokines.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.83-88.

Documentation
G protein-coupled receptors (GPCRs) constitute a vast protein family that 
encompasses a wide range of functions (including various autocrine, para-
crine and endocrine processes). They show considerable diversity at the 
sequence level, on the basis of which they can be separated into distinct 
groups. We use the term clan to describe the GPCRs, as they embrace a group
of families for which there are indications of evolutionary relationship, 
but between which there is no statistically significant similarity in 
sequence [1]. The currently known clan members include the rhodopsin-like 
GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating
pheromone receptors, and the metabotropic glutamate receptor family.
 
The rhodopsin-like GPCRs themselves represent a widespread protein family 
that includes hormone, neurotransmitter and light receptors, all of
which transduce extracellular signals through interaction with guanine
nucleotide-binding (G) proteins. Although their activating ligands vary 
widely in structure and character, the amino acid sequences of the 
receptors are very similar and are believed to adopt a common structural 
framework comprising 7 transmembrane (TM) helices [3-5]. 
 
Interleukin-8 (IL8) is a pro-inflammatory cytokine involved in the cellular
response to inflammation, being a powerful chemoattractant for neutrophils
[6]. There are 2 similar cell surface receptors for IL8: type 1 (IL-8RA) is
a high affinity receptor for IL8 alone; while type 2 (IL-8RB) is a high
affinity receptor for IL8, growth related gene (GRO) and neutrophil-
activating protein-2 (NAP-2). The affinity of type 1 receptors for IL8 is
higher than that of type 2 receptors [6,7]. The receptors are coupled to
Bordetella pertussis toxin-sensitive GTP-binding proteins [8]. Signal
transduction depends on the activation of a phospholipase C specific for
phosphatidylinositol-4,5-bisphosphate, producing 2 second messengers:
inositol triphosphate and diacylglycerol [8]. Inositol triphosphate induces
a rise in the levels of cytosolic free calcium, while diacylglycerol
activates protein kinase C, leading to activation of neutrophils [8].
 
IL8RB receptors are found in high density in neutrophils, monocytes, 
basophils, and melanoma cells, and in lower density in T-cells [9]. IL8
has been reported to stimulate the phosphoinositide pathway through an
uncharacterised G protein; pertussis toxin also inhibits several of its
actions [9]. The IL8RB receptor shares around 80% similarity with the
IL8RA receptor.
 
INTRLEUKN8AR is a 4-element fingerprint that provides a signature for the
interleukin 8B receptors. The fingerprint was derived from an initial
alignment of 7 sequences: the motifs were drawn from conserved sections
within both N- and C-terminal regions, focusing on those areas of the
alignment that characterise the interleukin 8B receptors but distinguish
them from the rest of the rhodopsin-like superfamily - motifs 1 and 2 lie
at the N-terminus; and motifs 3 and 4 lie at the C-terminus. A single
iteration on OWL28.1 was required to reach convergence, no further
sequences being identified beyond the starting set.
 
An update on SPTR37_9f identified a true set of 4 sequences.
Summary Information
4 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
44444
30000
20000
1234
True Positives
IL8B_HUMAN    IL8B_MOUSE    IL8B_RABIT    IL8B_RAT      
Sequence Titles
IL8B_HUMAN  HIGH AFFINITY INTERLEUKIN-8 RECEPTOR B (IL-8R B) (CXCR-2) (GRO/MGSA RECEPTOR) (IL-8 RECEPTOR TYPE 2) - HOMO SAPIENS (HUMAN). 
IL8B_MOUSE HIGH AFFINITY INTERLEUKIN-8 RECEPTOR B (IL-8R B) (CXCR-2) (GRO/MGSA RECEPTOR) - MUS MUSCULUS (MOUSE).
IL8B_RABIT HIGH AFFINITY INTERLEUKIN-8 RECEPTOR B (IL-8R B) (CXCR-2) (GRO/MGSA RECEPTOR) - ORYCTOLAGUS CUNICULUS (RABBIT).
IL8B_RAT HIGH AFFINITY INTERLEUKIN-8 RECEPTOR B (IL-8R B) (CXCR-2) (GRO/MGSA RECEPTOR) - RATTUS NORVEGICUS (RAT).
Scan History
OWL28_1    1  100  NSINGLE    
SPTR37_9f 2 5 NSINGLE
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
NMESDSFEDFW GGIL8RB 2 2 -
NMESDSFEDFW PTIL8RB 2 2 -
NMESDSFEDLW MMMCIL8RB 2 2 -
RVDNFSLEDFF IL8B_RAT 5 5 -
TWENYSYEDFF IL8B_RABIT 5 5 -
KVDKFNIEDFF IL8B_MOUSE 5 5 -
NMESDSFEDFW IL8B_HUMAN 5 5 -

Motif 2 width=12
Element Seqn Id St Int Rpt
DFSNYSYSTDLP IL8B_RABIT 17 1 -
DIDSYNYSSDPP IL8B_RAT 18 2 -
DFSNYSYSSDLP MMMCIL8RB 16 3 -
DLSNYSYSSTLP PTIL8RB 16 3 -
DLSNYSYSSALP GGIL8RB 16 3 -
DLSNYSYSSTLP IL8B_HUMAN 19 3 -
DLDIFNYSSGMP IL8B_MOUSE 18 2 -

Motif 3 width=9
Element Seqn Id St Int Rpt
CEPESLEIN GGIL8RB 36 8 -
CRPESLEIN MMMCIL8RB 36 8 -
CPSANLDIN IL8B_RAT 38 8 -
CRSESLETN IL8B_RABIT 37 8 -
CHSENLEIN IL8B_MOUSE 38 8 -
CEPESLEIN IL8B_HUMAN 39 8 -
CEPESLEIN PTIL8RB 36 8 -

Motif 4 width=16
Element Seqn Id St Int Rpt
LPKDSRPSFVGSSSGH MMMCIL8RB 337 292 -
LPKDSRPSFVGSSSGH PTIL8RB 337 292 -
LPKDSRPSFVGSSSGH IL8B_HUMAN 340 292 -
LAKEGRPSFVSSSSAN IL8B_MOUSE 339 292 -
LAKESRPSFVASSSGN IL8B_RABIT 338 292 -
LAKEGRPSFVGSSSAN IL8B_RAT 339 292 -
LPKDSRPSFVGSSSGH GGIL8RB 337 292 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
RVDNFSLEDFF IL8B_RAT 5 5 -
TWENYSYEDFF IL8B_RABIT 5 5 -
KVDKFNIEDFF IL8B_MOUSE 5 5 -
NMESDSFEDFW IL8B_HUMAN 5 5 -

Motif 2 width=12
Element Seqn Id St Int Rpt
DIDSYNYSSDPP IL8B_RAT 18 2 -
DFSNYSYSTDLP IL8B_RABIT 17 1 -
DLDIFNYSSGMP IL8B_MOUSE 18 2 -
DLSNYSYSSTLP IL8B_HUMAN 19 3 -

Motif 3 width=9
Element Seqn Id St Int Rpt
CPSANLDIN IL8B_RAT 38 8 -
CRSESLETN IL8B_RABIT 37 8 -
CHSENLEIN IL8B_MOUSE 38 8 -
CEPESLEIN IL8B_HUMAN 39 8 -

Motif 4 width=16
Element Seqn Id St Int Rpt
LAKEGRPSFVGSSSAN IL8B_RAT 339 292 -
LAKESRPSFVASSSGN IL8B_RABIT 338 292 -
LAKEGRPSFVSSSSAN IL8B_MOUSE 339 292 -
LPKDSRPSFVGSSSGH IL8B_HUMAN 340 292 -