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
[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 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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