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PR01526

Identifier
EDG6RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01526
No. of Motifs
8
Creation Date
21-MAY-2001
Title
EDG-6 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. GRALER, M.H., BERNHARDT, G. AND LIPP, M.
EDG6, a novel G protein-coupled receptor related to receptors for bioactive
lysophospholipids, is specifically expressed in lymphoid tissue.
GENOMICS 53(2) 164-169 (1998).

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-6 is expressed predominantly in lymphoid and haematopoietic tissues and
in lung, a distribution that is quite restricted relative to other EDG
family members [9]. Binding of S1P to the receptor leads to activation of
phospholipase C and MAP kinases in a pertussis toxin sensitive manner,
through coupling to proteins of the Gi class. Whether EDG-6 can couple to
any other G protein families is currently not known [6].
 
EDG6RECEPTOR is an 8-element fingerprint that provides a signature for the
EDG-6 sphingosine 1-phosphate receptor. The fingerprint was derived from an
initial alignment of 2 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-6 receptors but distinguish
them from the rest of the sphingosine 1-phosphate receptor family - motifs 1
and 2 reside at the N-terminus; motif 3 spans the second cytoplasmic loop,
leading into TM domain 4; motif 4 spans the third cytoplasmic loop; motif 5
encodes the third external loop; and motifs 6-8 lie 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
2 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
822222222
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
O95977        Q9Z0L1        
Sequence Titles
O95977      PUTATIVE G protein COUPLED RECEPTOR, EDG6 PRECURSOR - Homo sapiens (Human). 
Q9Z0L1 G PROTEIN-COUPLED RECEPTOR PRECURSOR - Mus musculus (Mouse).
Scan History
SPTR39_15f 1  80   NSINGLE    
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
PESCQQLAAGG O95977 10 10 -
PESCHRLAASG Q9Z0L1 12 12 -

Motif 2 width=13
Element Seqn Id St Int Rpt
GRLAGRGGPEDGG O95977 33 12 -
GRLASRGGSEDGG Q9Z0L1 35 12 -

Motif 3 width=14
Element Seqn Id St Int Rpt
AESGATKTSRVYGF O95977 152 106 -
AESGATKTSRVYGC Q9Z0L1 154 106 -

Motif 4 width=16
Element Seqn Id St Int Rpt
SGQKAPRPAARRKARR O95977 233 67 -
NGQKSPRPPARRKSRR Q9Z0L1 235 67 -

Motif 5 width=15
Element Seqn Id St Int Rpt
FGSNLWAQEYLRGMD O95977 276 27 -
FGSNVWAQEYLRGMD Q9Z0L1 278 27 -

Motif 6 width=14
Element Seqn Id St Int Rpt
CCGCLRLGMRGPGD O95977 323 32 -
CCGCLWLGLRGPGD Q9Z0L1 325 32 -

Motif 7 width=20
Element Seqn Id St Int Rpt
RAVEAHSGASTTDSSLRPRD O95977 340 3 -
RITEAHSGASTTDSSLRPRD Q9Z0L1 342 3 -

Motif 8 width=24
Element Seqn Id St Int Rpt
SFRGSRSLSFRMREPLSSISSVRS O95977 360 0 -
SFRTSRSLSFRMREPLSSISSVRS Q9Z0L1 362 0 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
PESCQQLAAGG O95977 10 10 -
PESCHRLAASG Q9Z0L1 12 12 -

Motif 2 width=13
Element Seqn Id St Int Rpt
GRLAGRGGPEDGG O95977 33 12 -
GRLASRGGSEDGG Q9Z0L1 35 12 -

Motif 3 width=14
Element Seqn Id St Int Rpt
AESGATKTSRVYGF O95977 152 106 -
AESGATKTSRVYGC Q9Z0L1 154 106 -

Motif 4 width=16
Element Seqn Id St Int Rpt
SGQKAPRPAARRKARR O95977 233 67 -
NGQKSPRPPARRKSRR Q9Z0L1 235 67 -

Motif 5 width=15
Element Seqn Id St Int Rpt
FGSNLWAQEYLRGMD O95977 276 27 -
FGSNVWAQEYLRGMD Q9Z0L1 278 27 -

Motif 6 width=14
Element Seqn Id St Int Rpt
CCGCLRLGMRGPGD O95977 323 32 -
CCGCLWLGLRGPGD Q9Z0L1 325 32 -

Motif 7 width=20
Element Seqn Id St Int Rpt
RAVEAHSGASTTDSSLRPRD O95977 340 3 -
RITEAHSGASTTDSSLRPRD Q9Z0L1 342 3 -

Motif 8 width=24
Element Seqn Id St Int Rpt
SFRGSRSLSFRMREPLSSISSVRS O95977 360 0 -
SFRTSRSLSFRMREPLSSISSVRS Q9Z0L1 362 0 -