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PR01525

Identifier
EDG5RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01525
No. of Motifs
7
Creation Date
21-MAY-2001
Title
EDG-5 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).
 
10. KUPPERMAN, E., AN, S., OSBORNE, N., WALDRON, S. AND STAINLER, D.Y.R.
A sphingosine-1-phosphate receptor regulates cell migration during
vertebrate heart development.
NATURE 406 192-195 (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].
 
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-5 is expressed abundantly in the heart and lung and at lower levels in
the adult brain. It is also expressed strongly in the embryonic brain [6,9].
Binding of S1P to EDG-5 activates G proteins of the Gi and Gq classes. G12
and G13 proteins are also constitutively activated by the receptor. These
couplings produce a wide range of cellular effects, including: increased
cyclic AMP and calcium levels, activation of MAP kinases and actin
rearrangement [6,8]. The receptor may have a role in neuronal development
and, in zebrafish, has been found to be involved in the control of cell
migration during development and organogenesis of the heart [10].
 
EDG5RECEPTOR is a 7-element fingerprint that provides a signature for the
EDG-5 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 cytoplasmic loop regions, focusing
on those areas of the alignment that characterise the EDG-5 receptors but
distinguish them from the rest of the sphingosine 1-phosphate receptor
family - motifs 1 and 2 lie at the N-terminus; motif 3 spans the second
cytoplasmic loop; motif 4 encodes the third cytoplasmic loop; and motifs 5-7
span 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  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
73333333
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
H218_RAT      O95136        Q9R236        
Sequence Titles
H218_RAT    PROBABLE G PROTEIN-COUPLED RECEPTOR H218 (AGR16) (LYSOSPHINGOLIPID RECEPTOR) - Rattus norvegicus (Rat). 
O95136 LYSOSPHINGOLIPID RECEPTOR EDG5 - Homo sapiens (Human).
Q9R236 LYSOPHOSPHOLIPID RECEPTOR B2 - Mus musculus (Mouse).
Scan History
SPTR39_15f 1  180  NSINGLE    
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
MGGLYSEYLNP Q9R236 1 1 -
MGSLYSEYLNP O95136 1 1 -

Motif 2 width=14
Element Seqn Id St Int Rpt
ETLDMQETTSRKVA Q9R236 23 11 -
ETLETQETTSRQVA O95136 23 11 -

Motif 3 width=12
Element Seqn Id St Int Rpt
VKLYGSDKSCRM Q9R236 137 100 -
VKLYGSDKSCRM O95136 137 100 -

Motif 4 width=12
Element Seqn Id St Int Rpt
RSSHADVAGPQT Q9R236 217 68 -
RSSHADMAAPQT O95136 217 68 -

Motif 5 width=13
Element Seqn Id St Int Rpt
CWRRGKGVTGRRG Q9R236 305 76 -
CWRPGVGVQGRRR O95136 305 76 -

Motif 6 width=11
Element Seqn Id St Int Rpt
GNPGHRLLPLR Q9R236 318 0 -
GTPGHHLLPLR O95136 319 1 -

Motif 7 width=20
Element Seqn Id St Int Rpt
LERGMHMPTSPTFLEGNTVV Q9R236 333 4 -
LERGMHMPTSPTFLEGNTVV O95136 334 4 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
MGGLYSEYLNP Q9R236 1 1 -
MGGLYSEYLNP H218_RAT 1 1 -
MGSLYSEYLNP O95136 1 1 -

Motif 2 width=14
Element Seqn Id St Int Rpt
ETLDMQETTSRKVA Q9R236 23 11 -
ETLDMQETPSRKVA H218_RAT 23 11 -
ETLETQETTSRQVA O95136 23 11 -

Motif 3 width=12
Element Seqn Id St Int Rpt
VKLYGSDKSCRM Q9R236 137 100 -
VKLYGSDKSCRM H218_RAT 137 100 -
VKLYGSDKSCRM O95136 137 100 -

Motif 4 width=12
Element Seqn Id St Int Rpt
RSSHADVAGPQT Q9R236 217 68 -
RSSHADVAGPQT H218_RAT 217 68 -
RSSHADMAAPQT O95136 217 68 -

Motif 5 width=13
Element Seqn Id St Int Rpt
CWRRGKGVTGRRG Q9R236 305 76 -
CWRQGKGATGRRG H218_RAT 305 76 -
CWRPGVGVQGRRR O95136 305 76 -

Motif 6 width=11
Element Seqn Id St Int Rpt
GNPGHRLLPLR Q9R236 318 0 -
GNPGHRLLPLR H218_RAT 318 0 -
GTPGHHLLPLR O95136 319 1 -

Motif 7 width=20
Element Seqn Id St Int Rpt
LERGMHMPTSPTFLEGNTVV Q9R236 333 4 -
LERGLHMPTSPTFLEGNTVV H218_RAT 333 4 -
LERGMHMPTSPTFLEGNTVV O95136 334 4 -