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PR01108

Identifier
CHEMOKINER3  [View Relations]  [View Alignment]  
Accession
PR01108
No. of Motifs
5
Creation Date
21-MAR-1999
Title
C-C chemokine receptor type 3 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00657 CCCHEMOKINER
INTERPRO; IPR002238
GCRDB; GCR_0988; GCR_1931; GCR_1934; GCR_1993; GCR_2529; GCR_1673

GCRDB; GCR_1695
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. COMBADIERE, C., AHUJA, S.K. AND MURPHY, P.M.
Cloning and functional expression of a human eosinophil CC chemokine 
receptor.
J.BIOL.CHEM. 270 16491-16494 (1995). 

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].
 
A human cDNA encoding an eosinophil-selective chemokine receptor (designated
CC chemokine receptor 3 (CC CKR3)) has been isolated [7]. When [Ca2+]i 
changes were monitored in stably transfected human embryonic kidney 293
cells, MIP-1 alpha and RANTES were both potent agonists for CC CKR3 and
CC CKR1 [7]. However, MIP-1 beta was also an agonist for CC CKR3 but not CC 
CKR1; MCP-3 was an agonist for CC CKR1 but not CC CKR3 [7]. CC CKR3 may be
one of the host factors responsible for selective recruitment of eosinophils
to sites of inflammation [7].  
 
CHEMOKINER3 is a 5-element fingerprint that provides a signature for type 3
C-C chemokine receptors. The fingerprint was derived from an initial 
alignment of 2 sequences: the motifs were drawn from conserved regions 
spanning virtually the full alignment length, focusing on those sections
that characterise the type 3 receptors but distinguish them from the rest of
the C-C chemokine receptor family - motif 1 resides at the N-terminus; motif
2 spans the C-terminus of TM domain 4 and part of the second external loop;
motif 3 lies within the third cytoplasmic loop; and motifs 4 and 5 reside
at the C-terminus. Two iterations on SPTR37_9f were required to reach
convergence, at which point a true set comprising 6 sequences was identified.
A single partial match was also found, Q89609, an equine Herpesvirus GPCR 
that matches motifs 2 and 3.
Summary Information
   6 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
566666
400000
300000
201100
12345
True Positives
CKR3_CERAE    CKR3_HUMAN    CKR3_MACMU    CKR3_MOUSE    
O54814 O55169
True Positive Partials
Codes involving 2 elements
Q89609
Sequence Titles
CKR3_CERAE  C-C CHEMOKINE RECEPTOR TYPE 3 (C-C CKR-3) (CC-CKR-3) (CCR-3) (CCR3) - CERCOPITHECUS AETHIOPS (GREEN MONKEY) (GRIVET). 
CKR3_HUMAN C-C CHEMOKINE RECEPTOR TYPE 3 (C-C CKR-3) (CC-CKR-3) (CCR-3) (CCR3) (EOSINOPHIL EOTAXIN RECEPTOR) - HOMO SAPIENS (HUMAN).
CKR3_MACMU C-C CHEMOKINE RECEPTOR TYPE 3 (C-C CKR-3) (CC-CKR-3) (CCR-3) (CCR3) - MACACA MULATTA (RHESUS MACAQUE).
CKR3_MOUSE PROBABLE C-C CHEMOKINE RECEPTOR TYPE 3 (C-C CKR-3) (CC-CKR-3) (CCR-3) (CCR3) (MACROPHAGE INFLAMMATORY PROTEIN-1 ALPHA RECEPTOR-LIKE 2) (MIP- 1 ALPHA RL2) - MUS MUSCULUS (MOUSE).
O54814 C-C CHEMOKINE RECEPTOR TYPE 3 (C-C CKR-3) (CC-CKR-3) (CCR-3) (CCR3) (CKR3) - RATTUS NORVEGICUS (RAT).
O55169 C-C CHEMOKINE RECEPTOR TYPE 3 (C-C CKR-3) (CC-CKR-3) (CCR-3) (CCR3) (CKR3) - RATTUS NORVEGICUS (RAT).

Q89609 G PROTEIN-COUPLED RECEPTOR - EQUINE HERPESVIRUS 2.
Scan History
SPTR37_9f  2  15   NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
VETFGTTSYY CKR3_HUMAN 8 8 -
VESFETTPYE CKR3_MOUSE 12 12 -

Motif 2 width=19
Element Seqn Id St Int Rpt
LAALPEFIFYETEELFEET CKR3_HUMAN 163 145 -
LAALPEFIFHESQDSFGEF CKR3_MOUSE 167 145 -

Motif 3 width=11
Element Seqn Id St Int Rpt
LLRCPSKKKYK CKR3_HUMAN 226 44 -
LLRCPNKKKHK CKR3_MOUSE 230 44 -

Motif 4 width=12
Element Seqn Id St Int Rpt
LGRYIPFLPSEK CKR3_HUMAN 324 87 -
LGKYIPFLPGEK CKR3_MOUSE 328 87 -

Motif 5 width=9
Element Seqn Id St Int Rpt
TAEPELSIV CKR3_HUMAN 346 10 -
TGEQEISVV CKR3_MOUSE 350 10 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
VETFETTPYE O55169 12 12 -
VETFETTPYE O54814 12 12 -
VETFGTTSYY CKR3_HUMAN 8 8 -
VESFETTPYE CKR3_MOUSE 12 12 -
VETFGPTSYD CKR3_MACMU 8 8 -
VETFGPTSYD CKR3_CERAE 8 8 -

Motif 2 width=19
Element Seqn Id St Int Rpt
LAALPEFIFHESQDNFGDL O55169 167 145 -
LAALPEFIFHESQDNFGDL O54814 167 145 -
LAALPEFIFYETEELFEET CKR3_HUMAN 163 145 -
LAALPEFIFHESQDSFGEF CKR3_MOUSE 167 145 -
LAALPEFIFYGTEKLFPKT CKR3_MACMU 163 145 -
LVALPEFIFYGTEELFPET CKR3_CERAE 163 145 -

Motif 3 width=11
Element Seqn Id St Int Rpt
LLRCPNKKKHK O55169 230 44 -
LLRCPNKKKHK O54814 230 44 -
LLRCPSKKKYK CKR3_HUMAN 226 44 -
LLRCPNKKKHK CKR3_MOUSE 230 44 -
LLRCPSKKKYK CKR3_MACMU 226 44 -
LLKCPSKKKYK CKR3_CERAE 226 44 -

Motif 4 width=12
Element Seqn Id St Int Rpt
LRKYISFLPGEK O55169 328 87 -
LRKYISFLPGEK O54814 328 87 -
LGRYIPFLPSEK CKR3_HUMAN 324 87 -
LGKYIPFLPGEK CKR3_MOUSE 328 87 -
LGKYIPFLPSEK CKR3_MACMU 324 87 -
LGRYIPFLPSEK CKR3_CERAE 324 87 -

Motif 5 width=9
Element Seqn Id St Int Rpt
TGEQEISVV O55169 350 10 -
TGEQEISVV O54814 350 10 -
TAEPELSIV CKR3_HUMAN 346 10 -
TGEQEISVV CKR3_MOUSE 350 10 -
TAEPELSIV CKR3_MACMU 346 10 -
TAEPELCIV CKR3_CERAE 346 10 -