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PR01560

Identifier
EDG7RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01560
No. of Motifs
7
Creation Date
16-AUG-2001
Title
EDG-7 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-7 is expressed at high levels in the testis, prostate, heart, pancreas
and frontal cerebral cortex in humans and at lower levels in the intestine,
lung and ovary. In mouse, expression is highest in the lung, kidney and
testis [6,8]. Binding of LPA to the receptor leads to increased cyclic AMP
and calcium levels and activation of MAP kinases. It is believed that these
effects are mediated by Gq and possibly Gi class proteins [6]. EDG-7 does
not appear to be able to couple to G12/13 or Gs [8].
 
EDG7RECEPTOR is a 7-element fingerprint that provides a signature for the
EDG-7 lysophosphatidic acid receptors. The fingerprint was derived from an
initial alignment of 3 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise the EDG-7 receptors but distinguish them from 
the rest of the lysophosphatidic acid receptor family - motif 1 resides at
the N-terminus; motif 2 lies in TM domain 1; motif 3 spans the third 
cytoplasmic loop; motif 4 lies in third external loop, leading into TM 
domain 7; and motifs 5-7 reside at the C-terminus. Two iterations on
SPTR39.22_17.3f were required to reach convergence, at which point a true
set comprising 4 sequences was identified.
Summary Information
4 codes involving  7 elements
0 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
74444444
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
Q9EQ31        Q9ESJ6        Q9NRB8        Q9UBY5        
Sequence Titles
Q9EQ31      LYSOPHOSPHATIDIC ACID RECEPTOR - Mus musculus (Mouse). 
Q9ESJ6 PUTATIVE G PROTEIN-COUPLED RECEPTOR SNGPCR32 - Rattus norvegicus (Rat).
Q9NRB8 G-PROTEIN COUPLED RECEPTOR EDG-7 - Homo sapiens (Human).
Q9UBY5 CALCIUM-MOBILIZING LYSOPHOSPHATIDIC ACID RECEPTOR LP-A3/EDG-7 - Homo sapiens (Human).
Scan History
SPTR39.22_17.3f 2  120  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
NTDTADEWTGTKL Q9ESJ6 9 9 -
NTDTADEWTGTKL Q9EQ31 18 18 -
NTDTVDDWTGTKL Q9UBY5 18 18 -

Motif 2 width=15
Element Seqn Id St Int Rpt
CVGTFFCLFIFFSNS Q9ESJ6 26 4 -
CVGTFFCLFIFFSNS Q9EQ31 35 4 -
CVGTFFCLFIFFSNS Q9UBY5 35 4 -

Motif 3 width=19
Element Seqn Id St Int Rpt
NVLSPHTSGSISRRRAPMK Q9ESJ6 209 168 -
NVLSPHTSGSISRRRAPMK Q9EQ31 218 168 -
NVLSPHTSGSISRRRTPMK Q9UBY5 218 168 -

Motif 4 width=13
Element Seqn Id St Int Rpt
NCKQCNVQHVKRW Q9ESJ6 256 28 -
NCKQCNVQHVKRW Q9EQ31 265 28 -
NCRQCGVQHVKRW Q9UBY5 265 28 -

Motif 5 width=13
Element Seqn Id St Int Rpt
ERHPSRIPSTIHS Q9ESJ6 309 40 -
ERRPSRNPSTIHS Q9EQ31 318 40 -
ERRPSRIPSTVLS Q9UBY5 317 39 -

Motif 6 width=13
Element Seqn Id St Int Rpt
SRSDTGSQYLEDS Q9ESJ6 321 -1 -
SRSETGSQYLEDS Q9EQ31 330 -1 -
SRSDTGSQYIEDS Q9UBY5 329 -1 -

Motif 7 width=13
Element Seqn Id St Int Rpt
SISQGQVCNKSSS Q9ESJ6 333 -1 -
SISQGPVCNKNGS Q9EQ31 342 -1 -
SISQGAVCNKSTS Q9UBY5 341 -1 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
NTDTADEWTGTKL Q9ESJ6 9 9 -
NTDTADEWTGTKL Q9EQ31 18 18 -
NTDTVDDWTGTKL Q9UBY5 18 18 -
NTDTVDDWTGTKL Q9NRB8 18 18 -

Motif 2 width=15
Element Seqn Id St Int Rpt
CVGTFFCLFIFFSNS Q9ESJ6 26 4 -
CVGTFFCLFIFFSNS Q9EQ31 35 4 -
CVGTFFCLFIFFSNS Q9UBY5 35 4 -
CVGTFFCLFIFFSNS Q9NRB8 35 4 -

Motif 3 width=19
Element Seqn Id St Int Rpt
NVLSPHTSGSISRRRAPMK Q9ESJ6 209 168 -
NVLSPHTSGSISRRRAPMK Q9EQ31 218 168 -
NVLSPHTSGSISRRRTPMK Q9UBY5 218 168 -
NVLSPHTSGSISRRRTPMK Q9NRB8 218 168 -

Motif 4 width=13
Element Seqn Id St Int Rpt
NCKQCNVQHVKRW Q9ESJ6 256 28 -
NCKQCNVQHVKRW Q9EQ31 265 28 -
NCRQCGVQHVKRW Q9UBY5 265 28 -
NCTQCGVQHVKRW Q9NRB8 265 28 -

Motif 5 width=13
Element Seqn Id St Int Rpt
ERHPSRIPSTIHS Q9ESJ6 309 40 -
ERRPSRNPSTIHS Q9EQ31 318 40 -
ERRPSRIPSTVLS Q9UBY5 317 39 -
DRRPSRLPSTILS Q9NRB8 318 40 -

Motif 6 width=13
Element Seqn Id St Int Rpt
SRSDTGSQYLEDS Q9ESJ6 321 -1 -
SRSETGSQYLEDS Q9EQ31 330 -1 -
SRSDTGSQYIEDS Q9UBY5 329 -1 -
SRSDTGSQYKEDS Q9NRB8 330 -1 -

Motif 7 width=13
Element Seqn Id St Int Rpt
SISQGQVCNKSSS Q9ESJ6 333 -1 -
SISQGPVCNKNGS Q9EQ31 342 -1 -
SISQGAVCNKSTS Q9UBY5 341 -1 -
SSSQGTVCNKNSS Q9NRB8 342 -1 -