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PR00427

Identifier
INTRLEUKIN8R  [View Relations]  [View Alignment]  
Accession
PR00427
No. of Motifs
7
Creation Date
13-DEC-1995  (UPDATE 10-JUN-1999)
Title
Interleukin-8 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00572 INTRLEUKN8AR; PR00573 INTRLEUKN8BR
INTERPRO; IPR000174
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).

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].
 
INTRLEUKIN8R is a 7-element fingerprint that provides a signature for the
IL8 receptors. The fingerprint was derived from an initial alignment of 8
sequences: the motifs were drawn from conserved sections within either loop
or TM regions, focusing on those areas of the alignment that characterise
the IL8 receptors but distinguish them from the rest of the rhodopsin-like
superfamily - motif 1 lies N-terminal to TM domain 1; motif 2 spans the
first cytoplasmic loop; motifs 3 and 4 lie at the N-termini of TM domains 3
and 4; motif 5 spans the C-terminus of TM domain 5 and the third cytoplasmic
loop; motif 6 spans the C-terminus of TM domain 6 and the third expternal
loop; and motif 7 lies at the C-terminus. A single iteration on OWL26.3 was
required to reach convergence, no further sequences being identified beyond 
the starting set.
 
An update on SPTR37_9f identified a true set of 9 sequences, and 2
partial matches.
Summary Information
   9 codes involving  7 elements
0 codes involving 6 elements
1 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
79999999
60000000
50111110
40000000
30000000
20001010
1234567
True Positives
IL8A_GORGO    IL8A_HUMAN    IL8A_PANTR    IL8A_RABIT    
IL8B_BOVIN IL8B_HUMAN IL8B_MOUSE IL8B_RABIT
IL8B_RAT
True Positive Partials
Codes involving 5 elements
IL8A_RAT
Codes involving 2 elements
O93239
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).
IL8B_BOVIN HIGH AFFINITY INTERLEUKIN-8 RECEPTOR B (IL-8R B) (CXCR-2) - BOS TAURUS (BOVINE).
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).

IL8A_RAT HIGH AFFINITY INTERLEUKIN-8 RECEPTOR A (IL-8R A) (CXCR-1) - RATTUS NORVEGICUS (RAT).

O93239 CXC CHEMOKINE RECEPTOR-2 - CYPRINUS CARPIO (COMMON CARP).
Scan History
OWL26_3    1  50   NSINGLE    
SPTR37_9f 2 11 NSINGLE
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
DYSPCLVVTQTLNKY IL8A_RABIT 31 31 -
DAAPCEPESLEINKY IL8B_HUMAN 30 30 -
DAVPCHSENLEINSY IL8B_MOUSE 34 34 -
DAAPCPSANLDINRY RATGMGSAR 34 34 -
DYSPCLVVTQTLNKY RABIL8RECE 31 31 -
DAAPCPSANLDINRY IL8B_RAT 34 34 -
DYSPCMLETETLNKY IL8A_HUMAN 26 26 -
DSAPCRSESLETNSY IL8B_RABIT 33 33 -

Motif 2 width=12
Element Seqn Id St Int Rpt
YNRSTCSVTDVY IL8B_MOUSE 74 25 -
YSRVGRSVTDVY IL8B_HUMAN 70 25 -
YSRSNRSVTDVY IL8A_RABIT 71 25 -
YNRSTCSVTDVY RATGMGSAR 74 25 -
YSRSTCSVTDVY IL8B_RABIT 73 25 -
YSRSNRSVTDVY RABIL8RECE 71 25 -
YSRVGRSVTDVY IL8A_HUMAN 66 25 -
YNRSTCSVTDVY IL8B_RAT 74 25 -

Motif 3 width=14
Element Seqn Id St Int Rpt
KVVSLVKEVNFYSG IL8A_RABIT 116 33 -
KVVSLVKEVNFYSG RABIL8RECE 115 32 -
KVFSFLQEITFYSS RATGMGSAR 119 33 -
KVVSLLKEVNFYSG IL8A_HUMAN 111 33 -
KVVSLVKEVNFYSG IL8B_RABIT 118 33 -
KVVSLLKEVNFYSG IL8B_HUMAN 115 33 -
KIFSYVKEVTFYSS IL8B_MOUSE 119 33 -
KVFSFLQEITFYSS IL8B_RAT 119 33 -

Motif 4 width=17
Element Seqn Id St Int Rpt
TAKWRMVLRILPHTFGF IL8A_HUMAN 195 70 -
TSKWRVVLRILPQTYGF RATGMGSAR 203 70 -
TSKWRVVLRILPQTYGF IL8B_RAT 203 70 -
TSRLRVVLRILPQTFGF IL8B_MOUSE 203 70 -
TAKWCMVLRILPHTFGF RABIL8RECE 199 70 -
TANWRMLLRILPQSFGF IL8B_HUMAN 199 70 -
TAKWRMVLRILPHTFGF IL8A_RABIT 200 70 -
TAKWRMVLRILPQTFGF IL8B_RABIT 202 70 -

Motif 5 width=16
Element Seqn Id St Int Rpt
GFTLRTLFKAHMGQKH RATGMGSAR 231 11 -
GFTLRTLFKAHMGQKH IL8A_HUMAN 223 11 -
VFTLRTLFQAHMGQKH IL8B_RABIT 230 11 -
GFTLRTLFQAHMGQKH IL8A_RABIT 228 11 -
GFTLRTLFKAHMGQKH IL8B_HUMAN 227 11 -
GFTLRTLFKAHMGQKH IL8B_MOUSE 231 11 -
GFTLRTLFKAHMGQKH IL8B_RAT 231 11 -
GFTLRTLFQAHMGQKH RABIL8RECE 227 11 -

Motif 6 width=17
Element Seqn Id St Int Rpt
DTLMRTKLIKETCERRD IL8B_MOUSE 273 26 -
DTLMRTKLIKETCERQN RATGMGSAR 273 26 -
DTLMRTHVIQETCQRRN RABIL8RECE 269 26 -
DTLMRTQVIQETCERRN IL8A_HUMAN 265 26 -
DTLMRTHVIQETCERRN IL8B_RABIT 272 26 -
DTLMRTHVIQETCQRRN IL8A_RABIT 270 26 -
DTLMRTKLIKETCERQN IL8B_RAT 273 26 -
DTLMRTQVIQETCERRN IL8B_HUMAN 269 26 -

Motif 7 width=17
Element Seqn Id St Int Rpt
GFLKILAMHGLVSKEFL IL8A_HUMAN 315 33 -
GFLKMLAARGLISKEFL RABIL8RECE 319 33 -
GLLKIMANYGLVSKEFL IL8B_RAT 320 30 -
GLLKIMATYGLVSKEFL IL8B_MOUSE 323 33 -
GLLKILAIHGLISKDSL IL8B_HUMAN 319 33 -
GFLKMLAARGLISKEFL IL8A_RABIT 320 33 -
GLLKILAAHGLISKEFL IL8B_RABIT 322 33 -
GLLKIMANYGLVSKEFL RATGMGSAR 323 33 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
DYSPCMLETETLNKY IL8A_HUMAN 26 26 -
DYSPCRLETETLNKY IL8A_GORGO 26 26 -
GYSPCRLETETLNKY IL8A_PANTR 26 26 -
DSAPCRSESLETNSY IL8B_RABIT 33 33 -
DYSPCLVVTQTLNKY IL8A_RABIT 31 31 -
DAAPCEPESLEINKY IL8B_HUMAN 30 30 -
DYSPCEISTETLNKY IL8B_BOVIN 35 35 -
DAVPCHSENLEINSY IL8B_MOUSE 34 34 -
DAAPCPSANLDINRY IL8B_RAT 34 34 -

Motif 2 width=12
Element Seqn Id St Int Rpt
YSRVGRSVTDVY IL8A_HUMAN 66 25 -
YSRGGRSVTDVY IL8A_GORGO 66 25 -
YSRVGRSVTDVY IL8A_PANTR 66 25 -
YSRSTCSVTDVY IL8B_RABIT 73 25 -
YSRSNRSVTDVY IL8A_RABIT 71 25 -
YSRVGRSVTDVY IL8B_HUMAN 70 25 -
YSRIGRSVTDVY IL8B_BOVIN 75 25 -
YNRSTCSVTDVY IL8B_MOUSE 74 25 -
YNRSTCSVTDVY IL8B_RAT 74 25 -

Motif 3 width=14
Element Seqn Id St Int Rpt
KVVSLLKEVNFYSG IL8A_HUMAN 111 33 -
KVVSLLKEVNFYSG IL8A_GORGO 111 33 -
KVVSLLKEVNFYSG IL8A_PANTR 111 33 -
KVVSLVKEVNFYSG IL8B_RABIT 118 33 -
KVVSLVKEVNFYSG IL8A_RABIT 116 33 -
KVVSLLKEVNFYSG IL8B_HUMAN 115 33 -
KVVSLLKEVNFYSG IL8B_BOVIN 120 33 -
KIFSYVKEVTFYSS IL8B_MOUSE 119 33 -
KVFSFLQEITFYSS IL8B_RAT 119 33 -

Motif 4 width=17
Element Seqn Id St Int Rpt
TAKWRMVLRILPHTFGF IL8A_HUMAN 195 70 -
TAKWRMVLRILPHTFGF IL8A_GORGO 195 70 -
TAKWRMVLRILPHTFGF IL8A_PANTR 195 70 -
TAKWRMVLRILPQTFGF IL8B_RABIT 202 70 -
TAKWRMVLRILPHTFGF IL8A_RABIT 200 70 -
TANWRMLLRILPQSFGF IL8B_HUMAN 199 70 -
TTKWRMIMRVLPQTFGF IL8B_BOVIN 204 70 -
TSRLRVVLRILPQTFGF IL8B_MOUSE 203 70 -
TSKWRVVLRILPQTYGF IL8B_RAT 203 70 -

Motif 5 width=16
Element Seqn Id St Int Rpt
GFTLRTLFKAHMGQKH IL8A_HUMAN 223 11 -
GFTLRTLFKAHMGQKH IL8A_GORGO 223 11 -
GFTLRTLFKAHMGQKH IL8A_PANTR 223 11 -
VFTLRTLFQAHMGQKH IL8B_RABIT 230 11 -
GFTLRTLFQAHMGQKH IL8A_RABIT 228 11 -
GFTLRTLFKAHMGQKH IL8B_HUMAN 227 11 -
GFTLRTLFSAQMGHKH IL8B_BOVIN 232 11 -
GFTLRTLFKAHMGQKH IL8B_MOUSE 231 11 -
GFTLRTLFKAHMGQKH IL8B_RAT 231 11 -

Motif 6 width=17
Element Seqn Id St Int Rpt
DTLMRTQVIQETCERRN IL8A_HUMAN 265 26 -
DTLMRTQVIQESCERRN IL8A_GORGO 265 26 -
DTLMRTQVIQESCERRN IL8A_PANTR 265 26 -
DTLMRTHVIQETCERRN IL8B_RABIT 272 26 -
DTLMRTHVIQETCQRRN IL8A_RABIT 270 26 -
DTLMRTQVIQETCERRN IL8B_HUMAN 269 26 -
DTLMRAHVIAETCQRRN IL8B_BOVIN 274 26 -
DTLMRTKLIKETCERRD IL8B_MOUSE 273 26 -
DTLMRTKLIKETCERQN IL8B_RAT 273 26 -

Motif 7 width=17
Element Seqn Id St Int Rpt
GFLKILAMHGLVSKEFL IL8A_HUMAN 315 33 -
GFLKILAMHGLVSKEFL IL8A_GORGO 315 33 -
GFLKILAMHGLVSKEFL IL8A_PANTR 315 33 -
GLLKILAAHGLISKEFL IL8B_RABIT 322 33 -
GFLKMLAARGLISKEFL IL8A_RABIT 320 33 -
GLLKILAIHGLISKDSL IL8B_HUMAN 319 33 -
GLLKIMAIHGLISKEFL IL8B_BOVIN 324 33 -
GLLKIMATYGLVSKEFL IL8B_MOUSE 323 33 -
GLLKIMANYGLVSKEFL IL8B_RAT 320 30 -