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PR01531

Identifier
CHEMOKINER9  [View Relations]  [View Alignment]  
Accession
PR01531
No. of Motifs
5
Creation Date
18-JUN-2001
Title
C-C chemokine receptor type 9 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. ZABALLOS, A., GUTIERREZ, J., VARONA, R., ARDAVIN, C. AND MARQUEZ G.
Cutting edge: identification of the orphan chemokine receptor GPR-9-6 as
CCR9, the receptor for the chemokine TECK.
J.IMMUNOL. 162 5671-5675 (1999).

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 orphan receptor GPR-9-6 was recently identified to be the target
of the novel chemokine, Thymus-Expressed ChemoKine (TECK). This receptor was
designated CC chemokine receptor 9 (CC CKR9). Human and murine forms of the
receptor have been cloned and found to be expressed very highly in the
thymus in both mature and immature T cells, with much lower levels being
found in the lymph nodes and spleen. Application of TECK to human or mouse
cells expressing CC CKR9 results in intracellular calcium mobilisation and
transfectant cell migration [7].
 
CHEMOKINER9 is a 5-element fingerprint that provides a signature for type 9
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 portion of the alignment, focusing on those sections
that characterise the type 9 receptors but distinguish them from the rest of
the C-C chemokine receptor family - motif 1 spans the C-terminus of the
third extracellular loop and TM domain 7; 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
CKR9_MOUSE    GC96_HUMAN    Q9UQQ6        
Sequence Titles
CKR9_MOUSE  C-C CHEMOKINE RECEPTOR TYPE 9 (C-C CKR-9) (CC-CKR-9) (CCR-9) (CHEMOKINE C-C RECEPTOR 10) - Mus musculus (Mouse). 
GC96_HUMAN PROBABLE G PROTEIN-COUPLED RECEPTOR GPR-9-6 - HOMO SAPIENS (HUMAN).
Q9UQQ6 CHEMOKINE RECEPTOR CCR9 (CC CHEMOKINE RECEPTOR 9A) - Homo sapiens (Human).
Scan History
SPTR39_15f 1  120  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
AVSTNIDICFQVTQTIA GC96_HUMAN 278 278 -
AVSTNIDICFQVTQTIA Q9UQQ6 290 290 -
TISTNIDICFQVTQTIA CKR9_MOUSE 290 290 -

Motif 2 width=11
Element Seqn Id St Int Rpt
RDLVKTLKNLG GC96_HUMAN 314 19 -
RDLVKTLKNLG Q9UQQ6 326 19 -
RDLVKTLKNLG CKR9_MOUSE 326 19 -

Motif 3 width=11
Element Seqn Id St Int Rpt
CISQAQWVSFT GC96_HUMAN 325 0 -
CISQAQWVSFT Q9UQQ6 337 0 -
CISQAQWVSFT CKR9_MOUSE 337 0 -

Motif 4 width=11
Element Seqn Id St Int Rpt
RREGSLKLSSM GC96_HUMAN 336 0 -
RREGSLKLSSM Q9UQQ6 348 0 -
RREGSLKLSSM CKR9_MOUSE 348 0 -

Motif 5 width=11
Element Seqn Id St Int Rpt
LLETTSGALSL GC96_HUMAN 347 0 -
LLETTSGALSL Q9UQQ6 359 0 -
LLETTSGALSL CKR9_MOUSE 359 0 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
AVSTNIDICFQVTQTIA GC96_HUMAN 278 278 -
AVSTNIDICFQVTQTIA Q9UQQ6 290 290 -
TISTNIDICFQVTQTIA CKR9_MOUSE 290 290 -

Motif 2 width=11
Element Seqn Id St Int Rpt
RDLVKTLKNLG GC96_HUMAN 314 19 -
RDLVKTLKNLG Q9UQQ6 326 19 -
RDLVKTLKNLG CKR9_MOUSE 326 19 -

Motif 3 width=11
Element Seqn Id St Int Rpt
CISQAQWVSFT GC96_HUMAN 325 0 -
CISQAQWVSFT Q9UQQ6 337 0 -
CISQAQWVSFT CKR9_MOUSE 337 0 -

Motif 4 width=11
Element Seqn Id St Int Rpt
RREGSLKLSSM GC96_HUMAN 336 0 -
RREGSLKLSSM Q9UQQ6 348 0 -
RREGSLKLSSM CKR9_MOUSE 348 0 -

Motif 5 width=11
Element Seqn Id St Int Rpt
LLETTSGALSL GC96_HUMAN 347 0 -
LLETTSGALSL Q9UQQ6 359 0 -
LLETTSGALSL CKR9_MOUSE 359 0 -