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PR01148

Identifier
EDG2RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01148
No. of Motifs
9
Creation Date
25-MAY-1999  (UPDATE 23-MAY-2001)
Title
EDG-2 lysophosphatidic acid receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01527 LPARECEPTOR
INTERPRO; IPR002277
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-2 was originally identified as a gene involved in neuron production from
embryonic cerebral cortex [6]. EDG-2 is widely distributed, with highest
levels in the brain (in which expression correlates with development of
oligodendrocytes and Schwann cells) [6]. In the periphery, EDG-2 is found in
many tissues, including the heart, kidney, testis, spleen and muscle in both
humans and mouse [8]. The receptor is also expressed in a number of cancers
[6]. Upon binding of LPA, EDG-2 couples to G proteins of the Gi, Gq and
G12/13 classes, to mediate a range of effects including: inhibition of
adenylyl cyclase; activation of phospholipase C, serum response element and
MAP kinases; and actomyosin stimulation. These processes lead to cell
rounding and proliferation [8].
 
EDG2RECEPTOR is a 9-element fingerprint that provides a signature for the
EDG-2 lysophosphatidic acid receptor. The fingerprint was derived from an
initial alignment of 5 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
areas of the alignment that characterise the EDG-2 receptors but distinguish
them from the rest of the LPA receptor family - motif 1 resides at the
N-terminus; motif 2 also encodes part of the N-terminus, leading into TM
domain 1; motif 3 lies in the first external loop; motif 4 spans the second
cytoplasmic loop; motif 5 resides in the second external loop; motif 6
encodes the third cytoplasmic loop; motif 7 lies at the C-terminus of TM
domain 7; and motifs 8 and 9 span the C-terminus. Two iterations on
SPTR39_15f were required to reach convergence, at which point a true set
comprising 7 sequences was identified.
Summary Information
7 codes involving  9 elements
0 codes involving 8 elements
0 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
9777777777
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
EDG2_BOVIN    EDG2_HUMAN    EDG2_MOUSE    EDG2_SHEEP    
O88584 Q9PU16 Q9PU17
Sequence Titles
EDG2_BOVIN  Lysophosphatidic acid receptor Edg-2 (LPA receptor 1) (LPA-1) (Rec1.3) - Bos taurus (Bovine). 
EDG2_HUMAN Lysophosphatidic acid receptor Edg-2 (LPA receptor 1) (LPA-1) - Homo sapiens (Human).
EDG2_MOUSE Lysophosphatidic acid receptor Edg-2 (LPA receptor 1) (LPA-1) (Rec1.3) (VZG-1) - Mus musculus (Mouse).
EDG2_SHEEP Lysophosphatidic acid receptor Edg-2 (LPA receptor 1) (LPA-1) - Ovis aries (Sheep).
O88584 LYSOPHOSPHATIDIC ACID RECEPTOR - Mus musculus (Mouse).
Q9PU16 LYSOPHOSPHATIDIC ACID RECEPTOR - Xenopus laevis (African clawed frog).
Q9PU17 LYSOPHOSPHATIDIC ACID RECEPTOR - Xenopus laevis (African clawed frog).
Scan History
SPTR39_15f 2  45   NSINGLE    
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
STSSPVISQPQFTAMNEQQC O88584 5 5 -
FVSEPIGMMSQTSAASESQC Q9PU16 7 7 -
FVSEPISMMSQTSAASESQC Q9PU17 7 7 -

Motif 2 width=15
Element Seqn Id St Int Rpt
YLATEWNTVSKLVMG O88584 40 15 -
YLDTEWNAVSKLVMG Q9PU16 42 15 -
YLATEWNAVSKLVMG Q9PU17 42 15 -

Motif 3 width=13
Element Seqn Id St Int Rpt
NTRRLTVNTWLLR O88584 112 57 -
NTRRLTVSTWLLR Q9PU16 114 57 -
NTRRLTVSTWLLR Q9PU17 114 57 -

Motif 4 width=15
Element Seqn Id St Int Rpt
ITVFRMQLHTRMSNR O88584 148 23 -
ITVFRMQLHTRMSNR Q9PU16 150 23 -
ITVFRMQLHTRMSNR Q9PU17 150 23 -

Motif 5 width=13
Element Seqn Id St Int Rpt
CICDIDHCSNMAP O88584 188 25 -
CICDLEHCSNMAP Q9PU16 190 25 -
CICDLEQCSNMAP Q9PU17 190 25 -

Motif 6 width=22
Element Seqn Id St Int Rpt
QRTMRMSRHSSGPRRNRDTMMS O88584 234 33 -
QRTMRMSRHSSGPRRNRDTMMS Q9PU16 236 33 -
QKTMRMSRHSSGPRRNRDTMMS Q9PU17 236 33 -

Motif 7 width=10
Element Seqn Id St Int Rpt
KEMSATFRQI O88584 316 60 -
KEMSATFKQI Q9PU16 318 60 -
KEMSATFKQI Q9PU17 318 60 -

Motif 8 width=18
Element Seqn Id St Int Rpt
QRNENPNGPTEGSDRSAS O88584 329 3 -
QRTENVNGPTEGSDRSAS Q9PU16 331 3 -
QRTENVNGPTEGSDRSAS Q9PU17 331 3 -

Motif 9 width=17
Element Seqn Id St Int Rpt
LNHTILAGVHSNDHSVV O88584 348 1 -
LNHTILAGVHSNDHSVV Q9PU16 350 1 -
LNHTILAGVHSNDHSVV Q9PU17 350 1 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
STSSPVISQPQFTAMNEQQC EDG2_MOUSE 5 5 -
STSSPVVSQPQFTAMNEPQC EDG2_SHEEP 5 5 -
STSSPVISQPQFTAMNEQQC O88584 5 5 -
FTSSPVVSQPQFTAMNEQQC EDG2_BOVIN 5 5 -
STSIPVISQPQFTAMNEPQC EDG2_HUMAN 5 5 -
FVSEPIGMMSQTSAASESQC Q9PU16 7 7 -
FVSEPISMMSQTSAASESQC Q9PU17 7 7 -

Motif 2 width=15
Element Seqn Id St Int Rpt
YLATEWNTVSKLVMG EDG2_MOUSE 40 15 -
YLATEWNTVSKLVMG EDG2_SHEEP 40 15 -
YLATEWNTVSKLVMG O88584 40 15 -
YLATEWNTVTKLVMG EDG2_BOVIN 40 15 -
HLATEWNTVSKLVMG EDG2_HUMAN 40 15 -
YLDTEWNAVSKLVMG Q9PU16 42 15 -
YLATEWNAVSKLVMG Q9PU17 42 15 -

Motif 3 width=13
Element Seqn Id St Int Rpt
NTRRLTVSTWLLR EDG2_MOUSE 112 57 -
NTRRLTVSTWLLR EDG2_SHEEP 112 57 -
NTRRLTVNTWLLR O88584 112 57 -
NTRRLTVSTWLLR EDG2_BOVIN 112 57 -
NTRRLTVSTWLLR EDG2_HUMAN 112 57 -
NTRRLTVSTWLLR Q9PU16 114 57 -
NTRRLTVSTWLLR Q9PU17 114 57 -

Motif 4 width=15
Element Seqn Id St Int Rpt
ITVFRMQLHTRMSNR EDG2_MOUSE 148 23 -
ITVFRMQLHTRMSNR EDG2_SHEEP 148 23 -
ITVFRMQLHTRMSNR O88584 148 23 -
ITVFRMQLHARMSNR EDG2_BOVIN 148 23 -
ITVFRMQLHTRMSNR EDG2_HUMAN 148 23 -
ITVFRMQLHTRMSNR Q9PU16 150 23 -
ITVFRMQLHTRMSNR Q9PU17 150 23 -

Motif 5 width=13
Element Seqn Id St Int Rpt
CICDIDHCSNMAP EDG2_MOUSE 188 25 -
CICDIENCSNMAP EDG2_SHEEP 188 25 -
CICDIDHCSNMAP O88584 188 25 -
CICDIENCSNMAP EDG2_BOVIN 188 25 -
CICDIENCSNMAP EDG2_HUMAN 188 25 -
CICDLEHCSNMAP Q9PU16 190 25 -
CICDLEQCSNMAP Q9PU17 190 25 -

Motif 6 width=22
Element Seqn Id St Int Rpt
QRTMRMSRHSSGPRRNRDTMMS EDG2_MOUSE 234 33 -
QRTMRMSRHSSGPRRNRDTMMS EDG2_SHEEP 234 33 -
QRTMRMSRHSSGPRRNRDTMMS O88584 234 33 -
QRTMRMSRHSSGPRRNRDTMMS EDG2_BOVIN 234 33 -
QRTMRMSRHSSGPRRNRDTMMS EDG2_HUMAN 234 33 -
QRTMRMSRHSSGPRRNRDTMMS Q9PU16 236 33 -
QKTMRMSRHSSGPRRNRDTMMS Q9PU17 236 33 -

Motif 7 width=10
Element Seqn Id St Int Rpt
KEMSATFRQI EDG2_MOUSE 316 60 -
KEMSATFRQI EDG2_SHEEP 316 60 -
KEMSATFRQI O88584 316 60 -
KEMSATFRQI EDG2_BOVIN 316 60 -
KEMSATFRQI EDG2_HUMAN 316 60 -
KEMSATFKQI Q9PU16 318 60 -
KEMSATFKQI Q9PU17 318 60 -

Motif 8 width=18
Element Seqn Id St Int Rpt
QRNENPNGPTEGSDRSAS EDG2_MOUSE 329 3 -
QRSENTSGPTEGSDRSAS EDG2_SHEEP 329 3 -
QRNENPNGPTEGSDRSAS O88584 329 3 -
QRSENTSGPTEGSDRSAS EDG2_BOVIN 329 3 -
QRSENPTGPTESSDRSAS EDG2_HUMAN 329 3 -
QRTENVNGPTEGSDRSAS Q9PU16 331 3 -
QRTENVNGPTEGSDRSAS Q9PU17 331 3 -

Motif 9 width=17
Element Seqn Id St Int Rpt
LNHTILAGVHSNDHSVV EDG2_MOUSE 348 1 -
LNHTILAGVHSNDHSVF EDG2_SHEEP 348 1 -
LNHTILAGVHSNDHSVV O88584 348 1 -
LNHTILAGVHSNDHSVV EDG2_BOVIN 348 1 -
LNHTILAGVHSNDHSVV EDG2_HUMAN 348 1 -
LNHTILAGVHSNDHSVV Q9PU16 350 1 -
LNHTILAGVHSNDHSVV Q9PU17 350 1 -