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PR00642

Identifier
EDG1RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR00642
No. of Motifs
9
Creation Date
09-DEC-1996  (UPDATE 23-MAY-2001)
Title
EDG-1 sphingosine 1-phosphate receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01523 S1PRECEPTOR
INTERPRO; IPR000987
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. PYNE, S. AND PYNE, N.J.
Sphingosine 1-phosphate signalling via the endothelial differentiation gene
family of G protein-coupled receptors.
PHARMACOL.THER. 88(2) 115-131 (2000).
 
9. ZHANG, G., CONTOS, J.J.A., WEINER, J.A., FUKUSHIMA, N. AND CHUN, J.
Comparative analysis of three murine G protein coupled receptors activated
by sphingosine-1-phosphate.
GENE 227(1) 89-99 (1999).
 
10. HLA, T. AND MACIAG, T.
An abundant transcript induced in differentiating human endothelial cells
encodes a polypeptide with structural similarities to G protein-coupled
receptors.
J.BIOL.CHEM. 265(16) 9308-9313 (1990).

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]. 
 
S1P is released from activated platelets and is also produced by a number
of other cell types in response to growth factors and cytokines [8]. It is
proposed to act both as an extracellular mediator and as an intracellular
second messenger. The cellular effects of S1P include growth related
effects, such as proliferation, differentiation, cell survival and
apoptosis, and cytoskeletal effects, such as chemotaxis, aggregation,
adhesion, morphological change and secretion. The molecule has been
implicated in control of angiogenesis, inflammation, heart-rate and tumour
progression, and may play an important role in a number of disease states,
such as atherosclerosis, and breast and ovarian cancer [8]. Recently, 5
G protein-coupled receptors have been identified that act as high affinity
receptors for S1P, and also as low affinity receptors for the related
lysophospholipid, SPC [6]. EDG-1, EDG-3, EDG-5 and EDG-8 share a high degree
of similarity, and are also referred to as lpB1, lpB3, lpB2 and lpB4,
respectively. EDG-6 is referred to as lpC1, reflecting its more distant
relationship to the other S1P receptors [6].
 
EDG-1 was the first member of the family to be cloned (from phorbol-ester
differentiated human endothelial cells); its ligand, however, was unknown,
so it was named endothelial differentiation gene (EDG) 1, reflecting its
potential function [10]. EDG-1 is expressed widely, with highest levels in
the brain, heart, lung, liver and spleen. Moderate levels are also found in
the thymus, kidney and muscle [9]. Within these regions, EDG-1 is expressed
in endothelial cells, vascular smooth muscle, fibroblasts, melanocytes and
cells of epithelioid origin [10]. Upon binding of S1P, the receptor can
couple to Gi1, Gi2, Gi3, Go and Gz type G proteins, leading to inhibition of
adenylyl cylase, phospholipase C activation and MAP kinase activation [6,8].
 
EDG1RECEPTOR is a 9-element fingerprint that provides a signature for the
EDG-1 sphingosine 1-phosphate receptor. The fingerprint was derived from an
initial alignment of 5 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-1 receptors but distinguish
them from the rest of the S1P receptor family - motifs 1 and 2 lie at the
N-terminus; motif 3 spans the first cytoplasmic loop; motif 4 is located in
the first external loop; motif 5 encodes the second cytoplasmic loop; motif
6 spans the third cytoplasmic loop; and motifs 7-9 reside 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
5 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
9555555555
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
EDG1_HUMAN    EDG1_MOUSE    EDG1_RAT      Q9NYN8        
Q9R235
Sequence Titles
EDG1_HUMAN  Sphingosine 1-phosphate receptor Edg-1 (Sphingosine 1-phosphate receptor 1) (S1P1) - Homo sapiens (Human). 
EDG1_MOUSE Sphingosine 1-phosphate receptor Edg-1 (Sphingosine 1-phosphate receptor 1) (S1P1) (Lysophospholipid receptor B1) - Mus musculus (Mouse).
EDG1_RAT Sphingosine 1-phosphate receptor Edg-1 (Sphingosine 1-phosphate receptor 1) (S1P1) - Rattus norvegicus (Rat).
Q9NYN8 G PROTEIN-COUPLED SPHINGOLIPID RECEPTOR - Homo sapiens (Human).
Q9R235 LYSOPHOSPHOLIPID RECEPTOR B1 - Mus musculus (Mouse).
Scan History
SPTR39_15f 1  25   NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
TSIPEVKALRSSVSDY Q9R235 4 4 -
TSVPLVKAHRSSVSDY Q9NYN8 4 4 -

Motif 2 width=17
Element Seqn Id St Int Rpt
GKLNIGAEKDHGIKLTS Q9R235 33 13 -
GKLNISADKENSIKLTS Q9NYN8 33 13 -

Motif 3 width=13
Element Seqn Id St Int Rpt
TIWKTKKFHRPMY Q9R235 69 19 -
TIWKTKKFHRPMY Q9NYN8 69 19 -

Motif 4 width=11
Element Seqn Id St Int Rpt
TTYKLTPAQWF Q9R235 108 26 -
TTYKLTPAQWF Q9NYN8 108 26 -

Motif 5 width=17
Element Seqn Id St Int Rpt
TMLKMKLHNGSNSSRSF Q9R235 145 26 -
TMLKMKLHNGSNNFRLF Q9NYN8 145 26 -

Motif 6 width=19
Element Seqn Id St Int Rpt
RSRRLTFRKNISKASRSSE Q9R235 231 69 -
RSRRLTFRKNISKASRSSE Q9NYN8 231 69 -

Motif 7 width=20
Element Seqn Id St Int Rpt
IVSCCKCPNGDSAGKFKRPI Q9R235 325 75 -
IMSCCKCPSGDSAGKFKRPI Q9NYN8 325 75 -

Motif 8 width=17
Element Seqn Id St Int Rpt
IPGMEFSRSKSDNSSHP Q9R235 345 0 -
IAGMEFSRSKSDNSSHP Q9NYN8 345 0 -

Motif 9 width=18
Element Seqn Id St Int Rpt
PQKDDGDNPETIMSSGNV Q9R235 361 -1 -
PQKDEGDNPETIMSSGNV Q9NYN8 361 -1 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
TSIPEVKALRSSVSDY Q9R235 4 4 -
TSIPEVKALRSSVSDY EDG1_MOUSE 4 4 -
TSIPVVKALRSQVSDY EDG1_RAT 5 5 -
TSVPLVKAHRSSVSDY EDG1_HUMAN 4 4 -
TSVPLVKAHRSSVSDY Q9NYN8 4 4 -

Motif 2 width=17
Element Seqn Id St Int Rpt
GKLNIGAEKDHGIKLTS Q9R235 33 13 -
GKLNIGAEKDHGIKLTS EDG1_MOUSE 33 13 -
GKLNIGVEKDHGIKLTS EDG1_RAT 34 13 -
GKLNISADKENSIKLTS EDG1_HUMAN 33 13 -
GKLNISADKENSIKLTS Q9NYN8 33 13 -

Motif 3 width=13
Element Seqn Id St Int Rpt
TIWKTKKFHRPMY Q9R235 69 19 -
TIWKTKKFHRPMY EDG1_MOUSE 69 19 -
TIWKTKKFHRPMY EDG1_RAT 70 19 -
TIWKTKKFHRPMY EDG1_HUMAN 69 19 -
TIWKTKKFHRPMY Q9NYN8 69 19 -

Motif 4 width=11
Element Seqn Id St Int Rpt
TTYKLTPAQWF Q9R235 108 26 -
TTYKLTPAQWF EDG1_MOUSE 108 26 -
TTYKLTPAQWF EDG1_RAT 109 26 -
TTYKLTPAQWF EDG1_HUMAN 108 26 -
TTYKLTPAQWF Q9NYN8 108 26 -

Motif 5 width=17
Element Seqn Id St Int Rpt
TMLKMKLHNGSNSSRSF Q9R235 145 26 -
TMLKMKLHNGSNSSRSF EDG1_MOUSE 145 26 -
TMLKMKLHNGSNSSRSF EDG1_RAT 146 26 -
TMLKMKLHNGSNNFRLF EDG1_HUMAN 145 26 -
TMLKMKLHNGSNNFRLF Q9NYN8 145 26 -

Motif 6 width=19
Element Seqn Id St Int Rpt
RSRRLTFRKNISKASRSSE Q9R235 231 69 -
RSRRLTFRKNISKGSRSSE EDG1_MOUSE 231 69 -
RSRRLTFRKNISKASRSSE EDG1_RAT 232 69 -
RSRRLTFRKNISKASRSSE EDG1_HUMAN 231 69 -
RSRRLTFRKNISKASRSSE Q9NYN8 231 69 -

Motif 7 width=20
Element Seqn Id St Int Rpt
IVSCCKCPNGDSAGKFKRPI Q9R235 325 75 -
IVSCCKCPNGDSAGKFKRPI EDG1_MOUSE 325 75 -
IISCCKCPNGDSAGKFKRPI EDG1_RAT 326 75 -
IMSCCKCPSGDSAGKFKRPI EDG1_HUMAN 324 74 -
IMSCCKCPSGDSAGKFKRPI Q9NYN8 325 75 -

Motif 8 width=17
Element Seqn Id St Int Rpt
IPGMEFSRSKSDNSSHP Q9R235 345 0 -
IPGMEFSRSKSDNSSHP EDG1_MOUSE 345 0 -
IPGMEFSRSKSDNSSHP EDG1_RAT 346 0 -
IAGMEFSRSKSDNSSHP EDG1_HUMAN 344 0 -
IAGMEFSRSKSDNSSHP Q9NYN8 345 0 -

Motif 9 width=18
Element Seqn Id St Int Rpt
PQKDDGDNPETIMSSGNV Q9R235 361 -1 -
PQKDDGDNPETIMSSGNV EDG1_MOUSE 361 -1 -
PQKDDGDNPETIMSSGNV EDG1_RAT 362 -1 -
PQKDEGDNPETIMSSGNV EDG1_HUMAN 360 -1 -
PQKDEGDNPETIMSSGNV Q9NYN8 361 -1 -