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PR01558

Identifier
CHEMOKINER11  [View Relations]  [View Alignment]  
Accession
PR01558
No. of Motifs
4
Creation Date
08-AUG-2001
Title
C-C chemokine receptor type 11 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, PP.83-88.
 
7. KHOJA, H,, WANG, G., NG, C., TUCKER, J., BROWN, T. AND SHYAMALA, V.
Cloning of CCRL1, an orphan seven transmembrane receptor related to 
chemokine receptors, expressed abundantly in the heart.
GENE 246 229-238 (2000).
 
8.SCHWEICKART, V.L., EPP, A., RAPORT, C.J. AND GRAY P.W.
CCR11 is a functional receptor for the monocyte chemoattractant protein 
family of chemokines.
J.BIOL.CHEM. 275(13) 9550-9556 (2000).

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 [1,2]. 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]. 
 
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].
 
C-C chemokine receptor type 11 (CC CKR11), formerly designated C-C chemokine
receptor like 1 (CCRL1), is expressed at high levels in the heart, small
intestine and lung. Lower levels of expression have been detected in the 
kidney, liver and colon [7,8]. The receptor binds the monocyte chemo-
attractant protein (MCP) family of chemokines with high affinity. In 
common with other C-C chemokine receptor family members, agonist binding 
elicits intracellular calcium mobilisation and subsequent transfectant 
cell migration [8].
 
CHEMOKINER11 is a 4-element fingerprint that provides a signature for type
11 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 11 receptors but distinguish them from the rest 
of the C-C chemokine receptor family - motif 1 lies in the extracellular
N-terminal region; motif 2 spans part of the extracellular N-terminal region
and part of TM domain 1; motif 3 lies partially in the second extracellular 
loop and partially in TM domain 5; and motif 4 resides within the
cytoplasmic C-terminal region. A single iteration on SPTR39.22_17.3f was 
required to reach convergence, no further sequences being identified beyond
the starting set.
Summary Information
2 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
42222
30000
20000
1234
True Positives
CKRB_BOVIN    CKRB_HUMAN    
Sequence Titles
CKRB_BOVIN                                                
CKRB_HUMAN C-C CHEMOKINE RECEPTOR TYPE 11 (C-C CKR-11) (CC-CKR-11) (CCR-11) (CHEMOKINE RECEPTOR-LIKE 1) (CCRL1) (CCX CKR) - Homo sapiens (Human).
Scan History
SPTR39.22_17.3f 1  300  NSINGLE    
Initial Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
MAVEYNQSTDYYYEENEMNDT CKRB_BOVIN 1 1 -
MALEQNQSTDYYYEENEMNGT CKRB_HUMAN 1 1 -

Motif 2 width=26
Element Seqn Id St Int Rpt
YSQYEVICIKEEVRKFAKVFLPAFFT CKRB_BOVIN 24 2 -
YSQYELICIKEDVREFAKVFLPVFLT CKRB_HUMAN 24 2 -

Motif 3 width=29
Element Seqn Id St Int Rpt
YHLGTSMKASIQILEICIGFIIPFLIMAV CKRB_BOVIN 190 140 -
RYLGTSMKALIQMLEICIGFVVPFLIMGV CKRB_HUMAN 190 140 -

Motif 4 width=20
Element Seqn Id St Int Rpt
KVAKKYGSWRRQRQNVEEIP CKRB_BOVIN 316 97 -
KVAKKYGSWRRQRQSVEEFP CKRB_HUMAN 316 97 -
Final Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
MAVEYNQSTDYYYEENEMNDT CKRB_BOVIN 1 1 -
MALEQNQSTDYYYEENEMNGT CKRB_HUMAN 1 1 -

Motif 2 width=26
Element Seqn Id St Int Rpt
YSQYEVICIKEEVRKFAKVFLPAFFT CKRB_BOVIN 24 2 -
YSQYELICIKEDVREFAKVFLPVFLT CKRB_HUMAN 24 2 -

Motif 3 width=29
Element Seqn Id St Int Rpt
YHLGTSMKASIQILEICIGFIIPFLIMAV CKRB_BOVIN 190 140 -
RYLGTSMKALIQMLEICIGFVVPFLIMGV CKRB_HUMAN 190 140 -

Motif 4 width=20
Element Seqn Id St Int Rpt
KVAKKYGSWRRQRQNVEEIP CKRB_BOVIN 316 97 -
KVAKKYGSWRRQRQSVEEFP CKRB_HUMAN 316 97 -