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PR01524

Identifier
EDG3RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01524
No. of Motifs
5
Creation Date
21-MAY-2001
Title
EDG-3 sphingosine 1-phosphate receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01523 S1PRECEPTOR
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).

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-3 is expressed at highest levels in the heart, kidney, placenta and
liver of humans, with lower levels found in the lung [6]. In mouse, highest
levels are found in the heart, lung, kidney and spleen, with lower levels in
the brain, thymus, muscle and testis [9]. The receptor has also been found
in rat Schwann cells, mouse embryonic brain and breast cancer cells [6].
Binding of S1P to EDG-3 leads to activation of Gi and Gq classes of G
proteins. G12 and G13 can also be constitutively activated by the receptor
[8]. These G proteins produce a range of effects, including: inhibition or
activation or adenylyl cylase, MAP kinase activation, serum response element
activation and phospholipase C activation, leading to cell proliferation and
survival [6,8].
 
EDG3RECEPTOR is a 5-element fingerprint that provides a signature for the
EDG-3 sphingosine 1-phosphate 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-3 receptors but distinguish
them from the rest of the sphingosine 1-phosphate receptor family - motif 1
lies at the N-terminus; motif 2 spans the second cytoplasmic loop; motif 3
is located in the second external loop; and motifs 4 and 5 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
3 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
533333
400000
300000
200000
12345
True Positives
EDG3_HUMAN    Q9PUQ8        Q9Z0U9        
Sequence Titles
EDG3_HUMAN  Sphingosine 1-phosphate receptor Edg-3 (S1P receptor Edg-3) (Endothelial differentiation G-protein coupled receptor 3) (Sphingosine 1-phosphate receptor 3) (S1P3) - Homo sapiens (Human). 
Q9PUQ8 EDG-3 - Fugu rubripes (Japanese pufferfish) (Takifugu rubripes).
Q9Z0U9 LYSOPHOSPHOLIPID RECEPTOR B3 - Mus musculus (Mouse).
Scan History
SPTR39_15f 1  300  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
YVGKLAGRLRDPPEGGT Q9Z0U9 24 24 -
YTGKLDHRPTVGTSPGT Q9PUQ8 13 13 -

Motif 2 width=17
Element Seqn Id St Int Rpt
TMIKMRPYDANKKHRVF Q9Z0U9 140 99 -
TMIKMRPYDASKNYRVF Q9PUQ8 130 100 -

Motif 3 width=11
Element Seqn Id St Int Rpt
KSSSRRVANHN Q9Z0U9 224 67 -
KSSSQKVSKHR Q9PUQ8 214 67 -

Motif 4 width=10
Element Seqn Id St Int Rpt
CGCLVKGKGT Q9Z0U9 314 79 -
CGVCYRGNGS Q9PUQ8 304 79 -

Motif 5 width=15
Element Seqn Id St Int Rpt
SPMQPALDPSRSKSS Q9Z0U9 326 2 -
SGNKQFQEPSRSRSK Q9PUQ8 317 3 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
YVGKLAGRLKEASEGST EDG3_HUMAN 24 24 -
YVGKLAGRLRDPPEGGT Q9Z0U9 24 24 -
YTGKLDHRPTVGTSPGT Q9PUQ8 13 13 -

Motif 2 width=17
Element Seqn Id St Int Rpt
TMIKMRPYDANKRHRVF EDG3_HUMAN 139 98 -
TMIKMRPYDANKKHRVF Q9Z0U9 140 99 -
TMIKMRPYDASKNYRVF Q9PUQ8 130 100 -

Motif 3 width=11
Element Seqn Id St Int Rpt
KSSSRKVANHN EDG3_HUMAN 223 67 -
KSSSRRVANHN Q9Z0U9 224 67 -
KSSSQKVSKHR Q9PUQ8 214 67 -

Motif 4 width=10
Element Seqn Id St Int Rpt
CNCLVRGRGA EDG3_HUMAN 314 80 -
CGCLVKGKGT Q9Z0U9 314 79 -
CGVCYRGNGS Q9PUQ8 304 79 -

Motif 5 width=15
Element Seqn Id St Int Rpt
SPIQPALDPSRSKSS EDG3_HUMAN 326 2 -
SPMQPALDPSRSKSS Q9Z0U9 326 2 -
SGNKQFQEPSRSRSK Q9PUQ8 317 3 -