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PR01109

Identifier
CHEMOKINER4  [View Relations]  [View Alignment]  
Accession
PR01109
No. of Motifs
8
Creation Date
21-MAR-1999
Title
C-C chemokine receptor type 4 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00657 CCCHEMOKINER
INTERPRO; IPR002239
GCRDB; GCR_2115; GCR_1714
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. HOOGEWERF, A., BLACK, D., PROUDFOOT, A.E., WELLS, T.N. AND POWER, C.A.
Molecular cloning of murine CC CKR-4 and high affinity binding of chemokines
to murine and human CC CKR-4.
BIOCHEM.BIOPHYS.RES.COMMUN. 218 337-343 (1996). 

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].
 
The murine homologue of human CC chemokine receptor-4 (CC CKR-4) has been
cloned [7]. The gene product is 85% identical to human CC CKR-4, to which
it shows similar binding characteristics and tissue distribution [7]. Murine
CC CKR-4 was detected in the thymus and T-cell lines by Northern blot 
analysis [7].
 
CHEMOKINER4 is an 8-element fingerprint that provides a signature for type 4
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 4 receptors but distinguish them from the rest of
the C-C chemokine receptor family - motifs 1 and 2 reside at the N-terminus;
motif 3 lies in the first external loop; motifs 4 and 5 span the second
external loop; motif 6 lies in the third external loop; and motifs 7 and 8
reside at the C-terminus. A single iteration on SPTR37_9f was required to 
reach convergence, no further sequences being identified beyond the starting
set.
Summary Information
2 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
822222222
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
CKR4_HUMAN    CKR4_MOUSE    
Sequence Titles
CKR4_HUMAN  C-C CHEMOKINE RECEPTOR TYPE 4 (C-C CKR-4) (CC-CKR-4) (CCR-4) (CCR4) (K5-5) - HOMO SAPIENS (HUMAN). 
CKR4_MOUSE C-C CHEMOKINE RECEPTOR TYPE 4 (C-C CKR-4) (CC-CKR-4) (CCR-4) (CCR4) - MUS MUSCULUS (MOUSE).
Scan History
SPTR37_9f  1  3    NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
DESIYSNYYLYESIPKP CKR4_HUMAN 12 12 -
DETVYNSYYFYESMPKP CKR4_MOUSE 12 12 -

Motif 2 width=12
Element Seqn Id St Int Rpt
TKEGIKAFGELF CKR4_HUMAN 30 1 -
TKEGIKAFGEVF CKR4_MOUSE 30 1 -

Motif 3 width=10
Element Seqn Id St Int Rpt
WGYYAADQWV CKR4_HUMAN 95 53 -
WGYYAADQWV CKR4_MOUSE 95 53 -

Motif 4 width=17
Element Seqn Id St Int Rpt
FSTCYTERNHTYCKTKY CKR4_HUMAN 175 70 -
FSTCYTEHNHTYCKTQY CKR4_MOUSE 175 70 -

Motif 5 width=17
Element Seqn Id St Int Rpt
YSLNSTTWKVLSSLEIN CKR4_HUMAN 191 -1 -
YSVNSTTWKVLSSLEIN CKR4_MOUSE 191 -1 -

Motif 6 width=16
Element Seqn Id St Int Rpt
LVELEVLQDCTFERYL CKR4_HUMAN 267 59 -
LVELEVLQDCTLERYL CKR4_MOUSE 267 59 -

Motif 7 width=20
Element Seqn Id St Int Rpt
FKTCRGLFVLCQYCGLLQIY CKR4_HUMAN 319 36 -
FRTCRGPLVLCKHCDFLQVY CKR4_MOUSE 319 36 -

Motif 8 width=21
Element Seqn Id St Int Rpt
YSADTPSSSYTQSTMDHDLHD CKR4_HUMAN 338 -1 -
YSADMSSSSYTQSTVDHDFRD CKR4_MOUSE 338 -1 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
DESIYSNYYLYESIPKP CKR4_HUMAN 12 12 -
DETVYNSYYFYESMPKP CKR4_MOUSE 12 12 -

Motif 2 width=12
Element Seqn Id St Int Rpt
TKEGIKAFGELF CKR4_HUMAN 30 1 -
TKEGIKAFGEVF CKR4_MOUSE 30 1 -

Motif 3 width=10
Element Seqn Id St Int Rpt
WGYYAADQWV CKR4_HUMAN 95 53 -
WGYYAADQWV CKR4_MOUSE 95 53 -

Motif 4 width=17
Element Seqn Id St Int Rpt
FSTCYTERNHTYCKTKY CKR4_HUMAN 175 70 -
FSTCYTEHNHTYCKTQY CKR4_MOUSE 175 70 -

Motif 5 width=17
Element Seqn Id St Int Rpt
YSLNSTTWKVLSSLEIN CKR4_HUMAN 191 -1 -
YSVNSTTWKVLSSLEIN CKR4_MOUSE 191 -1 -

Motif 6 width=16
Element Seqn Id St Int Rpt
LVELEVLQDCTFERYL CKR4_HUMAN 267 59 -
LVELEVLQDCTLERYL CKR4_MOUSE 267 59 -

Motif 7 width=20
Element Seqn Id St Int Rpt
FKTCRGLFVLCQYCGLLQIY CKR4_HUMAN 319 36 -
FRTCRGPLVLCKHCDFLQVY CKR4_MOUSE 319 36 -

Motif 8 width=21
Element Seqn Id St Int Rpt
YSADTPSSSYTQSTMDHDLHD CKR4_HUMAN 338 -1 -
YSADMSSSSYTQSTVDHDFRD CKR4_MOUSE 338 -1 -