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PR01528

Identifier
EDG4RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01528
No. of Motifs
6
Creation Date
21-MAY-2001
Title
EDG-4 lysophosphatidic acid receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01527 LPARECEPTOR
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. FUKUSHIMA, N., ISHII, I., CONTOS, J.J.A., WEINER, J.A. AND CHUN, J.
Lysophospholipid receptors.
ANNU.REV.PHARMACOL.TOXICOL. 41 507-534 (2001).
 
7. LYNCH, K.R. AND IM, D.-S.
Life on the edg.
TRENDS PHARMACOL.SCI 20(12) 473-475 (1999).
 
8. CONTOS, J.J.A., ISHII, I. AND CHUN, J.
Lysophosphatidic acid receptors.
MOL.PHARMACOL. 58(6) 1188-1196 (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]. 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].
 
Lysophospholipids (LPs), such as lysophosphatidic acid (LPA), sphingosine
1-phosphate (S1P) and sphingosylphosphorylcholine (SPC), have long been
known to act as signalling molecules in addition to their roles as
intermediates in membrane biosynthesis [6]. They have roles in the
regulation of cell growth, differentiation, apoptosis and development, and
have been implicated in a wide range of pathophysiological conditions,
including: blood clotting, corneal wounding, subarachinoid haemorrhage,
inflammation and colitis [7]. A number of G protein-coupled receptors bind
members of the lysophopholipid family - these include: the cannabinoid
receptors; platelet activating factor receptor; OGR1, an SPC receptor
identified in ovarian cancer cell lines; PSP24, an orphan receptor that has
been proposed to bind LPA; and at least 8 closely related receptors, the EDG
family, that bind LPA and S1P [6].
 
LPA is found in all cell types in small quantities (associated with membrane
biosynthesis) but is produced in significant quantities by some cellular
sources, accounting for the levels of LPA in serum. LPA is also found in
elevated levels in ovarian cancer ascites, and acts to stimulate
proliferation and promote survival of the cancer cells [8]. The effects of
LPA on the proliferation and morphology of a number of other cell types have
been well documented [6,8]. However, identification of the mechanisms by
which these effects are accomplished has been complicated by a number of
factors, such as: a lack of antagonists, difficulty in ligand-binding
experiments and the responsiveness of many cell types to LPA [8]. The
G protein-coupled receptors EDG-2, EDG-4 and EDG-7 have now been identified
as high affinity receptors for LPA. It has been suggested that these
receptors should now be referred to as lpA1, lpA2 and lpA3 respectively
[6,7].
 
EDG-4 is expressed at high levels in the testis and peripheral blood
leukocytes of humans, and the testis, kidney and embryonic brain in mouse.
Lower levels of expression are found in human pancreas, spleen, thymus and
prostate, and mouse heart, lung, spleen, thymus, stomach and brain [8].
Variant forms of the receptor are also expressed in cancer cells [6].
Binding of LPA to EDG-4 results in increased calcium levels, inhibition of
adenyly cylase, activation of MAP kinases and cell rounding, through
coupling to Gi/o, Gq/11 and G12/13 proteins [8].
 
EDG4RECEPTOR is a 6-element fingerprint that provides a signature for the
EDG-4 lysophosphatidic acid receptor. The fingerprint was derived from an
initial alignment of 3 sequences: the motifs were drawn from conserved
sections within N- and C-terminal and loop regions, focusing on those
areas of the alignment that characterise the EDG-4 receptors but distinguish
them from the rest of the lysophosphatidic acid receptor family - motif 1 
resides at the N-terminus, leading into TM domain 1; motif 2 lies in the
second external loop; motif 3 spans the C-terminal portion of the third
cytoplasmic loop; and motifs 4-6 lie at the 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  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6333333
5000000
4000000
3000000
2000000
123456
True Positives
O00543        O43431        Q9JL06        
Sequence Titles
O00543      R33799_1 (LYSOPHOSPHATIDIC ACID G PROTEIN-COUPLED RECEPTOR 4) - Homo sapiens (Human). 
O43431 G PROTEIN-COUPLED RECEPTOR EDG-4 - Homo sapiens (Human).
Q9JL06 LYSOPHOSPHATIDIC ACID RECEPTOR LPA2 - Mus musculus (Mouse).
Scan History
SPTR39_15f 1  80   NSINGLE    
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
ELSSHWRPKDVV O00543 23 23 -
ELSSHWRPKDVV O43431 23 23 -
ELSLHWRPKDVV Q9JL06 20 20 -

Motif 2 width=15
Element Seqn Id St Int Rpt
AHSWHCLCALDRCSR O00543 166 131 -
AHSWHCLCALDRCSR O43431 166 131 -
AHFWHCLCDLDSCSR Q9JL06 163 131 -

Motif 3 width=13
Element Seqn Id St Int Rpt
VSCHPRYRETTLS O00543 226 45 -
VSCHPRYRETTLS O43431 226 45 -
VSCHPRYRETTLS Q9JL06 223 45 -

Motif 4 width=13
Element Seqn Id St Int Rpt
ACLRQSTRESVHY O00543 313 74 -
ACLRQSTRESVHY O43431 313 74 -
MCLRWSSHKSARY Q9JL06 310 74 -

Motif 5 width=12
Element Seqn Id St Int Rpt
YTSSAQGGASTR O00543 325 -1 -
YTSSAQGGASTR O43431 325 -1 -
YSASAQTGASTR Q9JL06 322 -1 -

Motif 6 width=13
Element Seqn Id St Int Rpt
RIMLPENGHPLMD O00543 336 -1 -
RIMLPENGHPLMT O43431 336 -1 -
RIMLPENGRPLMD Q9JL06 333 -1 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
ELSSHWRPKDVV O00543 23 23 -
ELSSHWRPKDVV O43431 23 23 -
ELSLHWRPKDVV Q9JL06 20 20 -

Motif 2 width=15
Element Seqn Id St Int Rpt
AHSWHCLCALDRCSR O00543 166 131 -
AHSWHCLCALDRCSR O43431 166 131 -
AHFWHCLCDLDSCSR Q9JL06 163 131 -

Motif 3 width=13
Element Seqn Id St Int Rpt
VSCHPRYRETTLS O00543 226 45 -
VSCHPRYRETTLS O43431 226 45 -
VSCHPRYRETTLS Q9JL06 223 45 -

Motif 4 width=13
Element Seqn Id St Int Rpt
ACLRQSTRESVHY O00543 313 74 -
ACLRQSTRESVHY O43431 313 74 -
MCLRWSSHKSARY Q9JL06 310 74 -

Motif 5 width=12
Element Seqn Id St Int Rpt
YTSSAQGGASTR O00543 325 -1 -
YTSSAQGGASTR O43431 325 -1 -
YSASAQTGASTR Q9JL06 322 -1 -

Motif 6 width=13
Element Seqn Id St Int Rpt
RIMLPENGHPLMD O00543 336 -1 -
RIMLPENGHPLMT O43431 336 -1 -
RIMLPENGRPLMD Q9JL06 333 -1 -