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PR01523

Identifier
S1PRECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01523
No. of Motifs
7
Creation Date
21-MAY-2001
Title
Sphingosine 1-phosphate receptor family signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00642 EDG1RECEPTOR; PR01524 EDG3RECEPTOR; PR01525 EDG5RECEPTOR
PRINTS; PR01526 EDG6RECEPTOR; PR01561 EDG8RECEPTOR
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).

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].
 
S1PRECEPTOR is a 7-element fingerprint that provides a signature for the
sphingosine 1-phosphate receptor family. The fingerprint was derived from an
initial alignment of 10 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
areas of the alignment that characterise the sphingosine 1-phosphate
receptors but distinguish them from the rest of the rhodopsin-like
superfamily - motif 1 resides at the N-terminus; motif 2 lies at the
C-terminus of TM domain 2, leading into the first external loop; motif 3 is
located in the first external loop, leading into TM domain 3; motif 4
resides in the N-terminal portion of TM domain 5; motif 5 spans part of TM
domain 5, leading into the third cytoplasmic loop; motif 6 spans the third
external loop; and motif 7 lies at the C-terminus of TM domain 7. Two
iterations on SPTR39_15f were required to reach convergence, at which point
a true set comprising 15 sequences was identified. A single partial match
was also found, CB1A_FUGRU, a member of the closely related cannabinoid
receptor family that matches motifs 5 and 7.
Summary Information
  15 codes involving  7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
715151515151515
60000000
50000000
40000000
30000000
20000101
1234567
True Positives
EDG1_HUMAN    EDG1_MOUSE    EDG1_RAT      EDG3_HUMAN    
H218_RAT O95136 O95977 Q9JKM5
Q9NYN8 Q9PUQ8 Q9QY79 Q9R235
Q9R236 Q9Z0L1 Q9Z0U9
True Positive Partials
Codes involving 2 elements
CB1A_FUGRU
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).
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).
H218_RAT PROBABLE G PROTEIN-COUPLED RECEPTOR H218 (AGR16) (LYSOSPHINGOLIPID RECEPTOR) - Rattus norvegicus (Rat).
O95136 LYSOSPHINGOLIPID RECEPTOR EDG5 - Homo sapiens (Human).
O95977 PUTATIVE G protein COUPLED RECEPTOR, EDG6 PRECURSOR - Homo sapiens (Human).
Q9JKM5 SPHINGOSINE 1-PHOSPHATE RECEPTOR EDG-8 - Rattus norvegicus (Rat).
Q9NYN8 G PROTEIN-COUPLED SPHINGOLIPID RECEPTOR - Homo sapiens (Human).
Q9PUQ8 EDG-3 - Fugu rubripes (Japanese pufferfish) (Takifugu rubripes).
Q9QY79 GROWTH FACTOR-REGULATED G PROTEIN-COUPLED RECEPTOR NRG-1 - Rattus norvegicus (Rat).
Q9R235 LYSOPHOSPHOLIPID RECEPTOR B1 - Mus musculus (Mouse).
Q9R236 LYSOPHOSPHOLIPID RECEPTOR B2 - Mus musculus (Mouse).
Q9Z0L1 G PROTEIN-COUPLED RECEPTOR PRECURSOR - Mus musculus (Mouse).
Q9Z0U9 LYSOPHOSPHOLIPID RECEPTOR B3 - Mus musculus (Mouse).

CB1A_FUGRU CANNABINOID RECEPTOR TYPE 1A - Fugu rubripes (Japanese pufferfish) (Takifugu rubripes).
Scan History
SPTR39_15f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
GNYDIIVRHYNYT Q9R235 20 20 -
MINPLIYLHYNYT Q9PUQ8 2 2 -
PVSEVIVLHYNYT Q9JKM5 10 10 -
PVSEVIVLHYNYT Q9QY79 10 10 -
LNPNKVQEHYNYT O95136 9 9 -
LGNDTLREHYDYV Q9Z0U9 13 13 -
GHSLLIVLHYNHS Q9Z0L1 22 22 -
GHSRLIVLHYNHS O95977 20 20 -

Motif 2 width=10
Element Seqn Id St Int Rpt
YTANLLLSGA Q9R235 98 65 -
YLVNLLLSGE Q9PUQ8 83 68 -
YATNILLSGP Q9JKM5 89 66 -
YATNILLSGP Q9QY79 89 66 -
FVANTLLSGS O95136 86 64 -
YKVNILMSGR Q9Z0U9 93 67 -
YVVNVLLSGT Q9Z0L1 102 67 -
YLANVLLSGA O95977 99 66 -

Motif 3 width=12
Element Seqn Id St Int Rpt
FLREGSMFVALS Q9R235 118 10 -
FVREGSMFVTLG Q9PUQ8 103 10 -
FAREGGVFVALA Q9JKM5 109 10 -
FAREGGVFVALA Q9QY79 109 10 -
FAREGSASITLS O95136 106 10 -
FLREGSMFVALG Q9Z0U9 113 10 -
FLREGLLFMALA Q9Z0L1 122 10 -
FLREGLLFTALA O95977 119 10 -

Motif 4 width=11
Element Seqn Id St Int Rpt
KHYILFCTTVF Q9R235 200 70 -
KKYVAFCIIVF Q9PUQ8 185 70 -
KAYVLFCVLAF Q9JKM5 191 70 -
KAYVLFCVLAF Q9QY79 191 70 -
KHYVLCVVTIF O95136 188 70 -
KKYIAFLISIF Q9Z0U9 195 70 -
KGYVLFCVVVF Q9Z0L1 204 70 -
KRYILFCLVIF O95977 202 71 -

Motif 5 width=10
Element Seqn Id St Int Rpt
YCRIYSLVRT Q9R235 221 10 -
YARIYILVKS Q9PUQ8 206 10 -
YARIYCQVRA Q9JKM5 212 10 -
YARIYCQVRA Q9QY79 212 10 -
YVRIYCVVRS O95136 209 10 -
YARIYCLVKS Q9Z0U9 216 10 -
YGAIFRVVRA Q9Z0L1 225 10 -
YGAIFRLVQA O95977 223 10 -

Motif 6 width=12
Element Seqn Id St Int Rpt
KTCDILYKAEYF Q9R235 285 54 -
RPCPILYKADWF Q9PUQ8 262 46 -
RACPVLLQADPF Q9JKM5 281 59 -
RACPVLLQADPF Q9QY79 281 59 -
HSCPILYKAHYF O95136 262 43 -
KECSILFKSQWF Q9Z0U9 272 46 -
WAQEYLRGMDWI Q9Z0L1 283 48 -
WAQEYLRGMDWI O95977 281 48 -

Motif 7 width=11
Element Seqn Id St Int Rpt
TNKEMRRAFIR Q9R235 314 17 -
ASREMRRAFLG Q9PUQ8 291 17 -
TNRDLRHALLR Q9JKM5 310 17 -
TNRDLRHALLR Q9QY79 310 17 -
RSRDLRREVLR O95136 291 17 -
ASKEMRRAFFR Q9Z0U9 301 17 -
RSREVQRAVLA Q9Z0L1 312 17 -
RSREVCRAVLS O95977 310 17 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
GNYDIIVRHYNYT EDG1_MOUSE 20 20 -
GNYDIIVRHYNYT EDG1_RAT 21 21 -
GNYDIIVRHYNYT Q9R235 20 20 -
VNYDIIVRHYNYT EDG1_HUMAN 20 20 -
VNYDIIVRHYNYT Q9NYN8 20 20 -
LNPEKVQEHYNYT H218_RAT 9 9 -
MINPLIYLHYNYT Q9PUQ8 2 2 -
LNPEKVLEHYNYT Q9R236 9 9 -
PVSEVIVLHYNYT Q9JKM5 10 10 -
PVSEVIVLHYNYT Q9QY79 10 10 -
LNPNKVQEHYNYT O95136 9 9 -
RGNETLREHYQYV EDG3_HUMAN 13 13 -
LGNDTLREHYDYV Q9Z0U9 13 13 -
GHSLLIVLHYNHS Q9Z0L1 22 22 -
GHSRLIVLHYNHS O95977 20 20 -

Motif 2 width=10
Element Seqn Id St Int Rpt
YTANLLLSGA EDG1_MOUSE 98 65 -
YTANLLLSGA EDG1_RAT 99 65 -
YTANLLLSGA Q9R235 98 65 -
YTANLLLSGA EDG1_HUMAN 98 65 -
YTANLLLSGA Q9NYN8 98 65 -
FVANTLLSGP H218_RAT 86 64 -
YLVNLLLSGE Q9PUQ8 83 68 -
FVANTLLSGH Q9R236 86 64 -
YATNILLSGP Q9JKM5 89 66 -
YATNILLSGP Q9QY79 89 66 -
FVANTLLSGS O95136 86 64 -
YKVNILMSGK EDG3_HUMAN 92 66 -
YKVNILMSGR Q9Z0U9 93 67 -
YVVNVLLSGT Q9Z0L1 102 67 -
YLANVLLSGA O95977 99 66 -

Motif 3 width=12
Element Seqn Id St Int Rpt
FLREGSMFVALS EDG1_MOUSE 118 10 -
FLREGSMFVALS EDG1_RAT 119 10 -
FLREGSMFVALS Q9R235 118 10 -
FLREGSMFVALS EDG1_HUMAN 118 10 -
FLREGSMFVALS Q9NYN8 118 10 -
FAREGSAFITLS H218_RAT 106 10 -
FVREGSMFVTLG Q9PUQ8 103 10 -
FAREVSAFITLS Q9R236 106 10 -
FAREGGVFVALA Q9JKM5 109 10 -
FAREGGVFVALA Q9QY79 109 10 -
FAREGSASITLS O95136 106 10 -
FLREGSMFVALG EDG3_HUMAN 112 10 -
FLREGSMFVALG Q9Z0U9 113 10 -
FLREGLLFMALA Q9Z0L1 122 10 -
FLREGLLFTALA O95977 119 10 -

Motif 4 width=11
Element Seqn Id St Int Rpt
KHYILFCTTVF EDG1_MOUSE 200 70 -
KHYILFCTTVF EDG1_RAT 201 70 -
KHYILFCTTVF Q9R235 200 70 -
KHYILFCTTVF EDG1_HUMAN 200 70 -
KHYILFCTTVF Q9NYN8 200 70 -
KHYVLCVVTIF H218_RAT 188 70 -
KKYVAFCIIVF Q9PUQ8 185 70 -
KHYVLCVVTIF Q9R236 188 70 -
KAYVLFCVLAF Q9JKM5 191 70 -
KAYVLFCVLAF Q9QY79 191 70 -
KHYVLCVVTIF O95136 188 70 -
KKYIAFCISIF EDG3_HUMAN 194 70 -
KKYIAFLISIF Q9Z0U9 195 70 -
KGYVLFCVVVF Q9Z0L1 204 70 -
KRYILFCLVIF O95977 202 71 -

Motif 5 width=10
Element Seqn Id St Int Rpt
YCRIYSLVRT EDG1_MOUSE 221 10 -
YCRIYSLVRT EDG1_RAT 222 10 -
YCRIYSLVRT Q9R235 221 10 -
YCRIYSLVRT EDG1_HUMAN 221 10 -
YCRIYSLVRT Q9NYN8 221 10 -
YVRIYFVVRS H218_RAT 209 10 -
YARIYILVKS Q9PUQ8 206 10 -
YVRIYFVVRS Q9R236 209 10 -
YARIYCQVRA Q9JKM5 212 10 -
YARIYCQVRA Q9QY79 212 10 -
YVRIYCVVRS O95136 209 10 -
YARIYFLVKS EDG3_HUMAN 215 10 -
YARIYCLVKS Q9Z0U9 216 10 -
YGAIFRVVRA Q9Z0L1 225 10 -
YGAIFRLVQA O95977 223 10 -

Motif 6 width=12
Element Seqn Id St Int Rpt
KTCDILYKAEYF EDG1_MOUSE 285 54 -
KTCDILYKAEYF EDG1_RAT 286 54 -
KTCDILYKAEYF Q9R235 285 54 -
KTCDILFRAEYF EDG1_HUMAN 284 53 -
KTCDILFRAEYF Q9NYN8 285 54 -
RACPVLYKAHYF H218_RAT 262 43 -
RPCPILYKADWF Q9PUQ8 262 46 -
RACPVLYKAHYF Q9R236 262 43 -
RACPVLLQADPF Q9JKM5 281 59 -
RACPVLLQADPF Q9QY79 281 59 -
HSCPILYKAHYF O95136 262 43 -
QACPILFKAQWF EDG3_HUMAN 272 47 -
KECSILFKSQWF Q9Z0U9 272 46 -
WAQEYLRGMDWI Q9Z0L1 283 48 -
WAQEYLRGMDWI O95977 281 48 -

Motif 7 width=11
Element Seqn Id St Int Rpt
TNKEMRRAFIR EDG1_MOUSE 314 17 -
TNKEMRRAFIR EDG1_RAT 315 17 -
TNKEMRRAFIR Q9R235 314 17 -
TNKEMRRAFIR EDG1_HUMAN 313 17 -
TNKEMRRAFIR Q9NYN8 314 17 -
RSRDLRREVLR H218_RAT 291 17 -
ASREMRRAFLG Q9PUQ8 291 17 -
RSRDLRREVLR Q9R236 291 17 -
TNRDLRHALLR Q9JKM5 310 17 -
TNRDLRHALLR Q9QY79 310 17 -
RSRDLRREVLR O95136 291 17 -
ASKEMRRAFFR EDG3_HUMAN 301 17 -
ASKEMRRAFFR Q9Z0U9 301 17 -
RSREVQRAVLA Q9Z0L1 312 17 -
RSREVCRAVLS O95977 310 17 -