WORKLIST ENTRIES (1): INTRLEUKN8AR View alignment View Structure Interleukin 8A receptor signature Type of fingerprint: COMPOUND with 5 elements Links: PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3 PRINTS; PR00251 BACTRLOPSIN PRINTS; PR00427 INTRLEUKIN8R; PR00573 INTRLEUKN8BR INTERPRO; IPR001355 Creation date 10-SEP-1996; UPDATE 07-JUN-1999 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. 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 [1,2]. 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 . 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 . Signal transduction depends on the activation of a phospholipase C specific for phosphatidylinositol-4,5-bisphosphate, producing 2 second messengers: inositol triphosphate and diacylglycerol . Inositol triphosphate induces a rise in the levels of cytosolic free calcium, while diacylglycerol activates protein kinase C, leading to activation of neutrophils . IL8RA receptors are found in high density in neutrophils, monocytes, basophils, and melanoma cells, and in lower density in T-cells . IL8 has been reported to stimulate the phosphoinositide pathway through an uncharacterised G protein; pertussis toxin also inhibits several of its actions . 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 FINGERPRINT INDEX 5| 4 4 4 4 4 4| 0 0 0 0 0 3| 0 0 0 0 0 2| 0 0 0 0 0 --+-------------------------- | 1 2 3 4 5 True positives.. IL8A_GORGO IL8A_HUMAN IL8A_PANTR IL8A_RABIT PROTEIN TITLES IL8A_GORGO HIGH AFFINITY INTERLEUKIN-8 RECEPTOR A (IL-8R A) (IL-8 RECEP IL8A_HUMAN HIGH AFFINITY INTERLEUKIN-8 RECEPTOR A (IL-8R A) (IL-8 RECEP IL8A_PANTR HIGH AFFINITY INTERLEUKIN-8 RECEPTOR A (IL-8R A) (IL-8 RECEP IL8A_RABIT HIGH AFFINITY INTERLEUKIN-8 RECEPTOR A (IL-8R A) (CXCR-1) -
SCAN HISTORY OWL28_1 1 50 NSINGLE SPTR37_9f 2 5 NSINGLE INITIAL MOTIF SETS INTRLEUKN8AR1 Length of motif = 12 Motif number = 1 Interleukin 8A receptor motif I - 1 PCODE ST INT NMTDLWTWFEDE IL8A_RABIT 7 7 NMTDLWTWFEDE RABIL8RECE 7 7 NITDPQMWDFDD IL8A_HUMAN 3 3 INTRLEUKN8AR2 Length of motif = 14 Motif number = 2 Interleukin 8A receptor motif II - 1 PCODE ST INT EKDYSPCLVVTQTL IL8A_RABIT 29 10 EKDYSPCLVVTQTL RABIL8RECE 29 10 DEDYSPCMLETETL IL8A_HUMAN 24 9 INTRLEUKN8AR3 Length of motif = 14 Motif number = 3 Interleukin 8A receptor motif III - 1 PCODE ST INT FFLFRQVFSPNNSS IL8A_RABIT 176 133 FFLFRQVFSPNNSS RABIL8RECE 175 132 FFLFRQAYHPNNSS IL8A_HUMAN 171 133 INTRLEUKN8AR4 Length of motif = 11 Motif number = 4 Interleukin 8A receptor motif IV - 1 PCODE ST INT EFLTRHRVTSY IL8A_RABIT 334 144 EFLTRHRVTSY RABIL8RECE 333 144 EFLARHRVTSY IL8A_HUMAN 329 144 INTRLEUKN8AR5 Length of motif = 11 Motif number = 5 Interleukin 8A receptor motif V - 1 PCODE ST INT YTSSSTNVPSN IL8A_RABIT 344 -1 YTSSSTNVPSN RABIL8RECE 343 -1 YTSSSVNVSSN IL8A_HUMAN 339 -1 FINAL MOTIF SETS INTRLEUKN8AR1 Length of motif = 12 Motif number = 1 Interleukin 8A receptor motif I - 2 PCODE ST INT NITDPQMWDFDD IL8A_GORGO 3 3 NITDPQMWDFDD IL8A_HUMAN 3 3 NITDPQMWDFDD IL8A_PANTR 3 3 NMTDLWTWFEDE IL8A_RABIT 7 7 INTRLEUKN8AR2 Length of motif = 14 Motif number = 2 Interleukin 8A receptor motif II - 2 PCODE ST INT DEDYSPCRLETETL IL8A_GORGO 24 9 DEDYSPCMLETETL IL8A_HUMAN 24 9 DEGYSPCRLETETL IL8A_PANTR 24 9 EKDYSPCLVVTQTL IL8A_RABIT 29 10 INTRLEUKN8AR3 Length of motif = 14 Motif number = 3 Interleukin 8A receptor motif III - 2 PCODE ST INT FFLFRQAYHPNNSS IL8A_GORGO 171 133 FFLFRQAYHPNNSS IL8A_HUMAN 171 133 FFLFRQAYHPNNSS IL8A_PANTR 171 133 FFLFRQVFSPNNSS IL8A_RABIT 176 133 INTRLEUKN8AR4 Length of motif = 11 Motif number = 4 Interleukin 8A receptor motif IV - 2 PCODE ST INT EFLARHRVTSY IL8A_GORGO 329 144 EFLARHRVTSY IL8A_HUMAN 329 144 EFLARHRVTSY IL8A_PANTR 329 144 EFLTRHRVTSY IL8A_RABIT 334 144 INTRLEUKN8AR5 Length of motif = 11 Motif number = 5 Interleukin 8A receptor motif V - 2 PCODE ST INT YTSSSVNVSSN IL8A_GORGO 339 -1 YTSSSVNVSSN IL8A_HUMAN 339 -1 YTSSSVNVSSN IL8A_PANTR 339 -1 YTSSSTNVPSN IL8A_RABIT 344 -1
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