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PR01530

Identifier
CHEMOKINER8  [View Relations]  [View Alignment]  
Accession
PR01530
No. of Motifs
5
Creation Date
18-JUN-2001
Title
C-C chemokine receptor type 8 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00657 CCCHEMOKINER
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. WATSON, S. AND ARKINSTALL, S.
Chemokines.
In THE G protein-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, pp83-88.
 
7. GOYA, I., GUTIERREZ, J., VARONA, R., KREMER, L., ZABALLOS, A. AND MARQUEZ, G.
Identification of CCR8 as the specific receptor for the human beta-chemokine
i-309: cloning and molecular characterization of murine CCR8 as the receptor
for TCA-3.
J.IMMUNOL. 160 1975-1981 (1998).

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]. 
 
Chemokines are proteins that have important physiological and patho- 
physiological roles in a wide range of acute and chronic inflammatory
processes [6]. Their sequences are similar and are characterised by a 
4-cysteine motif: the family can be divided according to whether the
first 2 Cys residues are adjacent (the C-C family), or separated by an
intervening residue (the C-x-C family). C-C chemokines are chemoattractant
for monocytes but not for neutrophils. The C-C family includes human
monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal
T cell expressed and secreted (RANTES), and macrophage inflammatory 
proteins (MIP-1a and MIP-1b) [6].
 
C-C chemokine receptors are found in monocytes, lymphocytes, basophils and
eosinophils; mRNA is also found in some cell lines [6]. MCP-1 and MIP-1a
induce activation in low nanomolar concentrations and are highly selective
relative to C-x-C receptors. Calcium mobilisation has been demonstrated in
monocytes and in cells expressing the recombinant C-C receptor via an
uncharacterised G protein; pertussis toxin inhibits some of its actions [6].
 
Human and mouse cDNAs encoding novel C-C chemokine receptors, designated CC
chemokine receptor 8 (CC CKR8), have been isolated, which are expressed in
the thymus. The receptors bind the human chemokine I-309 and its murine
homologue TCA-3, respectively, with high affinity. Unlike most of the
chemokine receptors, these receptors appear to bind only a single chemokine.
In addition, like other C-C receptors, agonist binding elicits significant 
calcium mobilisation and subsequent transfectant cell migration that is 
sensitive to pertussis toxin inhibition [7].
 
CHEMOKINER8 is a 5-element fingerprint that provides a signature for type 8
C-C chemokine receptors. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved regions
spanning the C-terminal portion of the alignment, focusing on those sections
that characterise the type 8 receptors but distinguish them from the rest of
the C-C chemokine receptor family - motif 1 spans the C-terminus of TM
domain 6 and part of the third external loop; and motifs 2-5 reside at the
cytoplasmic C-terminus. A single iteration on SPTR39_15f was required to
reach convergence, no further sequences being identified beyond the starting
set.
Summary Information
3 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
533333
400000
300000
200000
12345
True Positives
CKR8_HUMAN    CKR8_MACMU    CKR8_MOUSE    
Sequence Titles
CKR8_HUMAN  C-C CHEMOKINE RECEPTOR TYPE 8 (C-C CKR-8) (CC-CKR-8) (CCR-8) (GPR-CY6) (GPRCY6) (CHEMOKINE RECEPTOR-LIKE 1) (CKR-L1) (TER1) (CMKBRL2) (CC- CHEMOKINE RECEPTOR CHEMR1) - Homo sapiens (Human). 
CKR8_MACMU C-C CHEMOKINE RECEPTOR TYPE 8 (C-C CKR-8) (CC-CKR-8) (CCR-8) - Macaca mulatta (Rhesus macaque).
CKR8_MOUSE C-C CHEMOKINE RECEPTOR TYPE 8 (C-C CKR-8) (CC-CKR-8) (CCR-8) - Mus musculus (Mouse).
Scan History
SPTR39_15f 1  130  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
FLTSLHSMHILDG CKR8_HUMAN 259 259 -
FLTSLHDLHILDG CKR8_MOUSE 257 257 -
FLTSLHSMHILDG CKR8_MACMU 260 260 -

Motif 2 width=11
Element Seqn Id St Int Rpt
KHLMDVFQKSC CKR8_MOUSE 307 37 -
KHLSEIFQKSC CKR8_MACMU 310 37 -
KHLSEIFQKSC CKR8_HUMAN 309 37 -

Motif 3 width=11
Element Seqn Id St Int Rpt
SQIFNYLGRQM CKR8_HUMAN 320 0 -
SHIFIYLGRQM CKR8_MACMU 321 0 -
SHIFLYLGRQM CKR8_MOUSE 318 0 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PRESCEKSSSCQ CKR8_HUMAN 331 0 -
PVGALERQLSSN CKR8_MOUSE 329 0 -
PRESCEKSSSCQ CKR8_MACMU 332 0 -

Motif 5 width=13
Element Seqn Id St Int Rpt
QHSFRSSSIDYIL CKR8_MACMU 344 0 -
QRSSHSSTLDDIL CKR8_MOUSE 341 0 -
QHSSRSSSVDYIL CKR8_HUMAN 343 0 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
FLTSLHSMHILDG CKR8_HUMAN 259 259 -
FLTSLHDLHILDG CKR8_MOUSE 257 257 -
FLTSLHSMHILDG CKR8_MACMU 260 260 -

Motif 2 width=11
Element Seqn Id St Int Rpt
KHLMDVFQKSC CKR8_MOUSE 307 37 -
KHLSEIFQKSC CKR8_MACMU 310 37 -
KHLSEIFQKSC CKR8_HUMAN 309 37 -

Motif 3 width=11
Element Seqn Id St Int Rpt
SQIFNYLGRQM CKR8_HUMAN 320 0 -
SHIFIYLGRQM CKR8_MACMU 321 0 -
SHIFLYLGRQM CKR8_MOUSE 318 0 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PRESCEKSSSCQ CKR8_HUMAN 331 0 -
PVGALERQLSSN CKR8_MOUSE 329 0 -
PRESCEKSSSCQ CKR8_MACMU 332 0 -

Motif 5 width=13
Element Seqn Id St Int Rpt
QHSFRSSSIDYIL CKR8_MACMU 344 0 -
QRSSHSSTLDDIL CKR8_MOUSE 341 0 -
QHSSRSSSVDYIL CKR8_HUMAN 343 0 -