| 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).
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| 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.
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| 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).
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