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PR01110

Identifier
CHEMOKINER5  [View Relations]  [View Alignment]  
Accession
PR01110
No. of Motifs
5
Creation Date
20-MAR-1999
Title
C-C chemokine receptor type 5 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00657 CCCHEMOKINER
INTERPRO; IPR002240
GCRDB; GCR_1923; GCR_1927; GCR_2116; GCR_2454; GCR_2497; GCR_1373

GCRDB; GCR_2539
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. RAPORT, C.J., GOSLING, J., SCHWEICKART, V.L., GRAY, P.W. AND CHARO, I.F.
Molecular cloning and functional characterization of a novel human CC 
chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha.
J.BIOL.CHEM. 271 17161-17166 (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].
 
A novel chemokine receptor, encoded 18 kilobase pairs downstream of the 
MCP-1 receptor (CCR2) gene on human chromosome 3p21, has been identified 
[7]. The deduced amino acid sequence of the receptor, designated CCR5, is
most similar to CCR2B, sharing 71% identical residues [7]. Transfected cells
expressing the receptor bind RANTES, MIP-1beta and MIP-1alpha with high
affinity, and generate inositol phosphates in response to these chemokines.
The same combination of chemokines has been shown potently to inhibit human
immunodeficiency virus replication in human peripheral blood leukocytes [7].
CCR5 is expressed in lymphoid organs, such as thymus and spleen, as well as
in peripheral blood leukocytes, including macrophages and T cells [7]. 
 
CHEMOKINER5 is a 5-element fingerprint that provides a signature for type 5
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 5 receptors but distinguish them from the rest of
the C-C chemokine receptor family - motif 1 resides at the N-terminus; 
motifs 2 and 3 span the second external loop; motif 4 lies within the third
external loop; and motif 5 resides at the C-terminus. Two iterations on
SPTR37_9f were required to reach convergence, at which point a true set
comprising 11 sequences was identified. A single partial match was also
found, O75303, a CC-chemokine receptor that matches motifs 1 and 2.
Summary Information
  11 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
51111111111
400000
300000
211000
12345
True Positives
CKR5_CERAE    CKR5_CERTO    CKR5_GORGO    CKR5_HUMAN    
CKR5_MACMU CKR5_MOUSE CKR5_PANTR CKR5_PAPHA
CKR5_RAT O77776 O77833
True Positive Partials
Codes involving 2 elements
O75303
Sequence Titles
CKR5_CERAE  C-C CHEMOKINE RECEPTOR TYPE 5 (C-C CKR-5) (CC-CKR-5) (CCR-5) (CCR5) - CERCOPITHECUS AETHIOPS (GREEN MONKEY) (GRIVET). 
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).
CKR5_GORGO C-C CHEMOKINE RECEPTOR TYPE 5 (C-C CKR-5) (CC-CKR-5) (CCR-5) (CCR5) - GORILLA GORILLA GORILLA (LOWLAND GORILLA).
CKR5_HUMAN C-C CHEMOKINE RECEPTOR TYPE 5 (C-C CKR-5) (CC-CKR-5) (CCR-5) (CCR5) (HIV-1 FUSION CO-RECEPTOR) (CHEMR13) - HOMO SAPIENS (HUMAN).
CKR5_MACMU C-C CHEMOKINE RECEPTOR TYPE 5 (C-C CKR-5) (CC-CKR-5) (CCR-5) (CCR5) - MACACA MULATTA (RHESUS MACAQUE), MACACA FASCICULARIS (CRAB EATING MACAQUE) (CYNOMOLGUS MONKEY), AND MACACA NEMESTRINA (PIG-TAILED MACAQUE).
CKR5_MOUSE C-C CHEMOKINE RECEPTOR TYPE 5 (C-C CKR-5) (CC-CKR-5) (CCR-5) (MIP-1 ALPHA RECEPTOR) - MUS MUSCULUS (MOUSE).
CKR5_PANTR C-C CHEMOKINE RECEPTOR TYPE 5 (C-C CKR-5) (CC-CKR-5) (CCR-5) (CCR5) - PAN TROGLODYTES (CHIMPANZEE).
CKR5_PAPHA C-C CHEMOKINE RECEPTOR TYPE 5 (C-C CKR-5) (CC-CKR-5) (CCR-5) (CCR5) - PAPIO HAMADRYAS (HAMADRYAS BABOON), AND PAPIO ANUBIS (OLIVE BABOON).
CKR5_RAT C-C CHEMOKINE RECEPTOR TYPE 5 (C-C CKR-5) (CC-CKR-5) (CCR-5) (MIP-1 ALPHA RECEPTOR) - RATTUS NORVEGICUS (RAT).
O77776 CHEMOKINE RECEPTOR CCR5 - CERCOCEBUS TORQUATUS TORQUATUS.
O77833 CHEMOKINE RECEPTOR CCR5 - CERCOCEBUS TORQUATUS TORQUATUS.

O75303 CC-CHEMOKINE RECEPTOR - HOMO SAPIENS (HUMAN).
Scan History
SPTR37_9f  2  12   NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
IYDINYYTSEPCQKINV CKR5_HUMAN 9 9 -
IYDIDYGMSAPCQKINV CKR5_MOUSE 11 11 -

Motif 2 width=21
Element Seqn Id St Int Rpt
TRSQKEGLHYTCSSHFPYSQY CKR5_HUMAN 167 141 -
TRSQKEGFHYTCSPHFPHTQY CKR5_MOUSE 169 141 -

Motif 3 width=14
Element Seqn Id St Int Rpt
YQFWKNFQTLKIVI CKR5_HUMAN 187 -1 -
YHFWKSFQTLKMVI CKR5_MOUSE 189 -1 -

Motif 4 width=8
Element Seqn Id St Int Rpt
SSSNRLDQ CKR5_MOUSE 272 69 -
SSSNRLDQ CKR5_HUMAN 270 69 -

Motif 5 width=15
Element Seqn Id St Int Rpt
KRCSIFQQDNPDRVS CKR5_MOUSE 324 44 -
KCCSIFQQEAPERAS CKR5_HUMAN 322 44 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
IYDIDYYTSEPCQKINV CKR5_PANTR 9 9 -
TYDIDYYTSEPCQKINV O77833 9 9 -
TYDIDYYTSEPCQKINV CKR5_MACMU 9 9 -
TYDIDYYTSEPCQKINV CKR5_CERTO 9 9 -
TYDIDYYTSEPCQKINV O77776 9 9 -
TYDIDYYTSEPCQKTNV CKR5_GORGO 9 9 -
TYDIDNYTSEPCQKINV CKR5_CERAE 9 9 -
TYDIDYYTSEPCQKINV CKR5_PAPHA 9 9 -
IYDINYYTSEPCQKINV CKR5_HUMAN 9 9 -
IYDIDYGMSAPCQKINV CKR5_MOUSE 11 11 -
IYDIDYSMSAPCQKVNV CKR5_RAT 11 11 -

Motif 2 width=21
Element Seqn Id St Int Rpt
TRSQREGLHYTCSSHFPYSQY CKR5_PAPHA 167 141 -
TRSQKEGLHYTCSSHFPYSQY CKR5_PANTR 167 141 -
TRSQREGLHYTCSSHFPYSQY O77833 159 133 -
TRSQREGLHYTCSSHFPYSQY CKR5_MACMU 167 141 -
TRSQREGLHYTCSPHFPYSQY CKR5_CERTO 167 141 -
TRSQREGLHYTCSPHFPYSQY O77776 167 141 -
TRSQKEGLHYTCSSHFPYSQY CKR5_GORGO 167 141 -
TRSQREGLHYTCSSHFPYSQY CKR5_CERAE 167 141 -
TRSQKEGLHYTCSSHFPYSQY CKR5_HUMAN 167 141 -
TRSQKEGFHYTCSPHFPHTQY CKR5_MOUSE 169 141 -
MRSQKEGSHYTCSPHFLHIQY CKR5_RAT 169 141 -

Motif 3 width=14
Element Seqn Id St Int Rpt
YRFWKHFQTLKMVI CKR5_RAT 189 -1 -
YQFWKNFQTLKIVI CKR5_PAPHA 187 -1 -
YQFWKNFQTLKIVI CKR5_PANTR 187 -1 -
YQFWKNFQTLKIVI O77833 179 -1 -
YQFWKNFQTLKMVI CKR5_MACMU 187 -1 -
YQFWKNFQTLKIVI CKR5_CERTO 187 -1 -
YQFWKNFQTLKIVI O77776 187 -1 -
YQFWKNFQTLKIVI CKR5_GORGO 187 -1 -
YQFWKNFQTLKIVI CKR5_CERAE 187 -1 -
YQFWKNFQTLKIVI CKR5_HUMAN 187 -1 -
YHFWKSFQTLKMVI CKR5_MOUSE 189 -1 -

Motif 4 width=8
Element Seqn Id St Int Rpt
SSSNRLDQ CKR5_HUMAN 270 69 -
SSSNRLDQ CKR5_PAPHA 270 69 -
SSSNRLDQ CKR5_PANTR 270 69 -
SSSNRLDQ O77833 262 69 -
SSSNRLDQ CKR5_MACMU 270 69 -
SSSNRLDQ CKR5_CERTO 270 69 -
SSSNRLDQ O77776 270 69 -
SSSNRLDQ CKR5_GORGO 270 69 -
SSSNRLDQ CKR5_CERAE 270 69 -
SSSNRLDQ CKR5_MOUSE 272 69 -
SSSNRLDQ CKR5_RAT 272 69 -

Motif 5 width=15
Element Seqn Id St Int Rpt
KCCSIFQQEAPERAS CKR5_PAPHA 322 44 -
KCCSIFQQEAPERAS CKR5_PANTR 322 44 -
KCCSIFQQEASERAS O77833 314 44 -
KCCSIFQQEAPERAS CKR5_MACMU 322 44 -
KCCSIFQQEASERAS CKR5_CERTO 322 44 -
KCCSIFQQEASERAS O77776 322 44 -
KCCSIFQQEAPERAS CKR5_GORGO 322 44 -
KCCSIFQQEAPERAS CKR5_CERAE 322 44 -
KCCSIFQQEAPERAS CKR5_HUMAN 322 44 -
KRCSIFQQDNPDRVS CKR5_MOUSE 324 44 -
KHCSIFQQVNPDRVS CKR5_RAT 324 44 -