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PR01106

Identifier
CHEMOKINER1  [View Relations]  [View Alignment]  
Accession
PR01106
No. of Motifs
8
Creation Date
21-MAR-1999
Title
C-C chemokine receptor type 1 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00657 CCCHEMOKINER
INTERPRO; IPR002236
GCRDB; GCR_0498; GCR_0557; GCR_0573; GCR_2470; GCR_1672; GCR_1698
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. NEOTE, K., DIGREGORIO, D., MAK, J.Y., HORUK, R. AND SCHALL, T.J.
Molecular cloning, functional expression, and signaling characteristics of 
a C-C chemokine receptor.
CELL 72 415-425 (1993). 

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 murine MIP-1 alpha, human MCP-1 and RANTES all bind to the C-C
CKR-1 with varying affinities [7]. Chemokine binding affinity does not
predict how well the ligand will transmit a signal through the receptor: 
RANTES and human MIP-1 alpha induce a similar intracellular calcium flux
but bind with disparate affinities, while MCP-1 and human MIP-1 beta induce
calcium mobilisation only at high concentrations [7]. C-C chemokines have
been shown to bind a C-C CKR-1-related gene product encoded by cytomegalo-
virus, suggesting a role for C-C chemokines in viral immunity [7].
 
CHEMOKINER1 is an 8-element fingerprint that provides a signature for type 1
C-C chemokine receptors. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved regions 
spanning virtually the full alignment length, focusing on those sections
that characterise the type 1 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 first cytoplasmic loop; motif 3 lies within the first external
loop; motifs 4 and 5 span the second external loop; motifs 6 and 7 lie in
the third cytoplasmic and external loops respectively; and motif 8 resides
at the C-terminus. A single iteration on SPTR37_9f was required to reach
convergence, no further sequences being identified beyond the starting set.
Three partial matches were found: CKRV_MOUSE is a murine macrophage
inflammatory protein that matches motifs 2,4, 7 and 8; and CKR5_CERTO and
CKR3_MOUSE are type 5 and type 3 chemokine receptors, respectively, that
each match 2 motifs.
Summary Information
   3 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
1 codes involving 4 elements
0 codes involving 3 elements
2 codes involving 2 elements
Composite Feature Index
833333333
700000000
600000000
500000000
401010011
300000000
201001101
12345678
True Positives
CKR1_HUMAN    CKR1_MACMU    CKR1_MOUSE    
True Positive Partials
Codes involving 4 elements
CKRV_MOUSE
Codes involving 2 elements
CKR3_MOUSE CKR5_CERTO
Sequence Titles
CKR1_HUMAN  C-C CHEMOKINE RECEPTOR TYPE 1 (C-C CKR-1) (CC-CKR-1) (CCR-1) (CCR1) (MACROPHAGE INFLAMMATORY PROTEIN-1 ALPHA RECEPTOR) (MIP-1ALPHA-R) (RANTES-R) (HM145) (LD78 RECEPTOR) - HOMO SAPIENS (HUMAN). 
CKR1_MACMU C-C chemokine receptor type 1 (C-C CKR-1) (CC-CKR-1) (CCR-1) (CCR1) - Macaca mulatta (Rhesus macaque).
CKR1_MOUSE C-C CHEMOKINE RECEPTOR TYPE 1 (C-C CKR-1) (CC-CKR-1) (CCR-1) (CCR1) (MACROPHAGE INFLAMMATORY PROTEIN-1 ALPHA RECEPTOR) (MIP-1ALPHA-R) (RANTES-R) - MUS MUSCULUS (MOUSE).

CKRV_MOUSE C-C CHEMOKINE RECEPTOR (MACROPHAGE INFLAMMATORY PROTEIN-1 ALPHA RECEPTOR-LIKE 1) - MUS MUSCULUS (MOUSE).

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).
CKR5_CERTO C-C CHEMOKINE RECEPTOR TYPE 5 (C-C CKR-5) (CC-CKR-5) (CCR-5) (CCR5) - CERCOCEBUS TORQUATUS ATYS (RED-CROWNED MANGABEY) (SOOTY MANGABEY).
Scan History
SPTR37_9f  1  7    NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
ETPNTTEDYDTTTEFD CKR1_HUMAN 2 2 -
ETPNTTEDYDMITEFD CKR1_MACMU 2 2 -
EISDFTEAYPTTTEFD CKR1_MOUSE 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
LVQYKRLKNMTSI CKR1_HUMAN 59 41 -
LVQYKRLKNMTNI CKR1_MACMU 59 41 -
LMQHRRLQSMTSI CKR1_MOUSE 59 41 -

Motif 3 width=11
Element Seqn Id St Int Rpt
IDYKLKDDWVF CKR1_HUMAN 91 19 -
IYYKSTDDWIF CKR1_MACMU 91 19 -
IDYKLKDDWIF CKR1_MOUSE 91 19 -

Motif 4 width=14
Element Seqn Id St Int Rpt
LYFSKTQWEFTHHT CKR1_HUMAN 169 67 -
MYFSKTQWNIVRHS CKR1_MACMU 169 67 -
LYFFKAQWEFTHRT CKR1_MOUSE 169 67 -

Motif 5 width=13
Element Seqn Id St Int Rpt
SLHFPHESLREWK CKR1_HUMAN 184 1 -
NIHFPYESFQQWK CKR1_MACMU 184 1 -
SPHFPYKSLKQWK CKR1_MOUSE 184 1 -

Motif 6 width=13
Element Seqn Id St Int Rpt
KILLRRPNEKKSK CKR1_HUMAN 224 27 -
KILLRRPNEKKSK CKR1_MACMU 224 27 -
RILLRRPSEKKVK CKR1_MOUSE 224 27 -

Motif 7 width=14
Element Seqn Id St Int Rpt
SVFQDFLFTHECEQ CKR1_HUMAN 262 25 -
SVFQEFLFTHLCEQ CKR1_MACMU 262 25 -
SAFQDVLFTNQCEQ CKR1_MOUSE 262 25 -

Motif 8 width=18
Element Seqn Id St Int Rpt
LRQLFHRRVAVHLVKWLP CKR1_HUMAN 312 36 -
LRQLFHRRVAVHLVKWLP CKR1_MACMU 312 36 -
LRQLFQRHVAIPLAKWLP CKR1_MOUSE 312 36 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
ETPNTTEDYDTTTEFD CKR1_HUMAN 2 2 -
ETPNTTEDYDMITEFD CKR1_MACMU 2 2 -
EISDFTEAYPTTTEFD CKR1_MOUSE 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
LVQYKRLKNMTSI CKR1_HUMAN 59 41 -
LVQYKRLKNMTNI CKR1_MACMU 59 41 -
LMQHRRLQSMTSI CKR1_MOUSE 59 41 -

Motif 3 width=11
Element Seqn Id St Int Rpt
IDYKLKDDWVF CKR1_HUMAN 91 19 -
IYYKSTDDWIF CKR1_MACMU 91 19 -
IDYKLKDDWIF CKR1_MOUSE 91 19 -

Motif 4 width=14
Element Seqn Id St Int Rpt
LYFSKTQWEFTHHT CKR1_HUMAN 169 67 -
MYFSKTQWNIVRHS CKR1_MACMU 169 67 -
LYFFKAQWEFTHRT CKR1_MOUSE 169 67 -

Motif 5 width=13
Element Seqn Id St Int Rpt
SLHFPHESLREWK CKR1_HUMAN 184 1 -
NIHFPYESFQQWK CKR1_MACMU 184 1 -
SPHFPYKSLKQWK CKR1_MOUSE 184 1 -

Motif 6 width=13
Element Seqn Id St Int Rpt
KILLRRPNEKKSK CKR1_HUMAN 224 27 -
KILLRRPNEKKSK CKR1_MACMU 224 27 -
RILLRRPSEKKVK CKR1_MOUSE 224 27 -

Motif 7 width=14
Element Seqn Id St Int Rpt
SVFQDFLFTHECEQ CKR1_HUMAN 262 25 -
SVFQEFLFTHLCEQ CKR1_MACMU 262 25 -
SAFQDVLFTNQCEQ CKR1_MOUSE 262 25 -

Motif 8 width=18
Element Seqn Id St Int Rpt
LRQLFHRRVAVHLVKWLP CKR1_HUMAN 312 36 -
LRQLFHRRVAVHLVKWLP CKR1_MACMU 312 36 -
LRQLFQRHVAIPLAKWLP CKR1_MOUSE 312 36 -