SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR01529

Identifier
CHEMOKINER6  [View Relations]  [View Alignment]  
Accession
PR01529
No. of Motifs
5
Creation Date
18-JUN-2001
Title
C-C chemokine receptor type 6 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. BABA, M., IMAI, T. NISHIMURA, M., KAKIZAKI, M., TAKAGI, S., HIESHIMA, K.,
NOMIYAMA, H. AND YOSHIE, O.
Identification of CCR6, the specific receptor for a novel
lymphocyte-directed CC chemokine LARC.
J.BIOL.CHEM. 272 14893-14898 (1997).

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 novel C-C chemokine, Liver and Activation-Regulated Chemokine (LARC)
functions as a chemoattractant for lymphocytes that express a class of
receptor specifically binding to LARC with high affinity. This class of
receptor has been identified as the orphan receptor GPR-CY4 and
consequently renamed CC chemokine receptor 6 (CC CKR6). Like most other C-C
chemokine receptors, agonist binding elicits an inward calcium flux and
migration in cells transfected with the receptor. Unusually for a chemokine
receptor, CC CKR6 appears to bind only LARC of the known chemokines [7].
 
CHEMOKINER6 is a 5-element fingerprint that provides a signature for type 6
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 half of the alignment, focusing on those sections
that characterise the type 6 receptors but distinguish them from the rest of
the C-C chemokine receptor family - motif 1 spans the second extracellular
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
CKR6_HUMAN    O54689        Q9R1V0        
Sequence Titles
CKR6_HUMAN  C-C CHEMOKINE RECEPTOR TYPE 6 (C-C CKR-6) (CC-CKR-6) (CCR-6) (LARC RECEPTOR) (GPR-CY4) (GPRCY4) (CHEMOKINE RECEPTOR-LIKE 3) (CKR-L3) (DRY6) - Homo sapiens (Human). 
O54689 G PROTEIN-COUPLED RECEPTOR KY411 - MUS MUSCULUS (MOUSE).
Q9R1V0 CC CHEMOKINE LARC SPECIFIC RECEPTOR - Mus musculus (Mouse).
Scan History
SPTR39_15f 1  210  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
EPRYRSVSEPITWK O54689 190 190 -
EPRYRSVSEPITWK Q9R1V0 190 190 -
EPKYQTVSEPIRWK CKR6_HUMAN 198 198 -

Motif 2 width=10
Element Seqn Id St Int Rpt
NYFMKIMKDV O54689 317 113 -
NYFMKIMKDV Q9R1V0 317 113 -
NYFLKILKDL CKR6_HUMAN 325 113 -

Motif 3 width=10
Element Seqn Id St Int Rpt
WCMRRKNKMP O54689 327 0 -
WCMRRKNKMP Q9R1V0 327 0 -
WCVRRKYKSS CKR6_HUMAN 335 0 -

Motif 4 width=11
Element Seqn Id St Int Rpt
GFLCARVYSES O54689 337 0 -
GFLCARVYSES Q9R1V0 337 0 -
GFSCAGRYSEN CKR6_HUMAN 345 0 -

Motif 5 width=19
Element Seqn Id St Int Rpt
ISRQTSETVENDNASSFTM O54689 349 1 -
ISRQTSETVENDNASSFTM Q9R1V0 349 1 -
ISRQTSETADNDNASSFTM CKR6_HUMAN 356 0 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
EPRYRSVSEPITWK O54689 190 190 -
EPRYRSVSEPITWK Q9R1V0 190 190 -
EPKYQTVSEPIRWK CKR6_HUMAN 198 198 -

Motif 2 width=10
Element Seqn Id St Int Rpt
NYFMKIMKDV O54689 317 113 -
NYFMKIMKDV Q9R1V0 317 113 -
NYFLKILKDL CKR6_HUMAN 325 113 -

Motif 3 width=10
Element Seqn Id St Int Rpt
WCMRRKNKMP O54689 327 0 -
WCMRRKNKMP Q9R1V0 327 0 -
WCVRRKYKSS CKR6_HUMAN 335 0 -

Motif 4 width=11
Element Seqn Id St Int Rpt
GFLCARVYSES O54689 337 0 -
GFLCARVYSES Q9R1V0 337 0 -
GFSCAGRYSEN CKR6_HUMAN 345 0 -

Motif 5 width=19
Element Seqn Id St Int Rpt
ISRQTSETVENDNASSFTM O54689 349 1 -
ISRQTSETVENDNASSFTM Q9R1V0 349 1 -
ISRQTSETADNDNASSFTM CKR6_HUMAN 356 0 -