SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR00572

Identifier
INTRLEUKN8AR  [View Relations]  [View Alignment]  
Accession
PR00572
No. of Motifs
5
Creation Date
10-SEP-1996  (UPDATE 07-JUN-1999)
Title
Interleukin 8A receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00427 INTRLEUKIN8R
INTERPRO; IPR001355
GCRDB; GCR_0107; GCR_0108; GCR_0298; GCR_0175; GCR_0696
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].
 
IL8RA 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 IL8RA receptor shares around 80% similarity with the
IL8RB receptor.
 
INTRLEUKN8AR is a 5-element fingerprint that provides a signature for the
interleukin 8A receptors. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved sections
within either loop or N- and C-terminal regions, focusing on those areas
of the alignment that characterise the interleukin 8A receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motifs 1
and 2 lie at the N-terminus; motif 3 spans the C-terminus of TM domain 4,
leading into the second external loop; and motifs 4 and 5 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. A single 
partial match was also found, BTU19947, a bovine interleukin-8 receptor
that has characteristics of both IL8RA and IL8RB sequences.
 
An update on SPTR37_9f identified a true set of 4 sequences.
Summary Information
4 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
544444
400000
300000
200000
12345
True Positives
IL8A_GORGO    IL8A_HUMAN    IL8A_PANTR    IL8A_RABIT    
Sequence Titles
IL8A_GORGO  HIGH AFFINITY INTERLEUKIN-8 RECEPTOR A (IL-8R A) (IL-8 RECEPTOR TYPE 1) (CXCR-1) (CDW128) - GORILLA GORILLA GORILLA (LOWLAND GORILLA), AND PONGO PYGMAEUS (ORANGUTAN). 
IL8A_HUMAN HIGH AFFINITY INTERLEUKIN-8 RECEPTOR A (IL-8R A) (IL-8 RECEPTOR TYPE 1) (CXCR-1) (CDW128) - HOMO SAPIENS (HUMAN).
IL8A_PANTR HIGH AFFINITY INTERLEUKIN-8 RECEPTOR A (IL-8R A) (IL-8 RECEPTOR TYPE 1) (CXCR-1) (CDW128) - PAN TROGLODYTES (CHIMPANZEE).
IL8A_RABIT HIGH AFFINITY INTERLEUKIN-8 RECEPTOR A (IL-8R A) (CXCR-1) - ORYCTOLAGUS CUNICULUS (RABBIT).
Scan History
OWL28_1    1  50   NSINGLE    
SPTR37_9f 2 5 NSINGLE
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
NMTDLWTWFEDE IL8A_RABIT 7 7 -
NITDPQMWDFDD IL8A_HUMAN 3 3 -
NMTDLWTWFEDE RABIL8RECE 7 7 -

Motif 2 width=14
Element Seqn Id St Int Rpt
DEDYSPCMLETETL IL8A_HUMAN 24 9 -
EKDYSPCLVVTQTL RABIL8RECE 29 10 -
EKDYSPCLVVTQTL IL8A_RABIT 29 10 -

Motif 3 width=14
Element Seqn Id St Int Rpt
FFLFRQAYHPNNSS IL8A_HUMAN 171 133 -
FFLFRQVFSPNNSS RABIL8RECE 175 132 -
FFLFRQVFSPNNSS IL8A_RABIT 176 133 -

Motif 4 width=11
Element Seqn Id St Int Rpt
EFLTRHRVTSY RABIL8RECE 333 144 -
EFLARHRVTSY IL8A_HUMAN 329 144 -
EFLTRHRVTSY IL8A_RABIT 334 144 -

Motif 5 width=11
Element Seqn Id St Int Rpt
YTSSSTNVPSN RABIL8RECE 343 -1 -
YTSSSTNVPSN IL8A_RABIT 344 -1 -
YTSSSVNVSSN IL8A_HUMAN 339 -1 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
NITDPQMWDFDD IL8A_GORGO 3 3 -
NITDPQMWDFDD IL8A_HUMAN 3 3 -
NITDPQMWDFDD IL8A_PANTR 3 3 -
NMTDLWTWFEDE IL8A_RABIT 7 7 -

Motif 2 width=14
Element Seqn Id St Int Rpt
DEDYSPCRLETETL IL8A_GORGO 24 9 -
DEDYSPCMLETETL IL8A_HUMAN 24 9 -
DEGYSPCRLETETL IL8A_PANTR 24 9 -
EKDYSPCLVVTQTL IL8A_RABIT 29 10 -

Motif 3 width=14
Element Seqn Id St Int Rpt
FFLFRQAYHPNNSS IL8A_GORGO 171 133 -
FFLFRQAYHPNNSS IL8A_HUMAN 171 133 -
FFLFRQAYHPNNSS IL8A_PANTR 171 133 -
FFLFRQVFSPNNSS IL8A_RABIT 176 133 -

Motif 4 width=11
Element Seqn Id St Int Rpt
EFLARHRVTSY IL8A_GORGO 329 144 -
EFLARHRVTSY IL8A_HUMAN 329 144 -
EFLARHRVTSY IL8A_PANTR 329 144 -
EFLTRHRVTSY IL8A_RABIT 334 144 -

Motif 5 width=11
Element Seqn Id St Int Rpt
YTSSSVNVSSN IL8A_GORGO 339 -1 -
YTSSSVNVSSN IL8A_HUMAN 339 -1 -
YTSSSVNVSSN IL8A_PANTR 339 -1 -
YTSSSTNVPSN IL8A_RABIT 344 -1 -