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PR01527

Identifier
LPARECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01527
No. of Motifs
6
Creation Date
21-MAY-2001
Title
Lysophosphatidic acid receptor family signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01148 EDG2RECEPTOR; PR01528 EDG4RECEPTOR; PR01560 EDG7RECEPTOR
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. CONTOS, J.J.A., ISHII, I. AND CHUN, J.
Lysophosphatidic acid receptors.
MOL.PHARMACOL. 58(6) 1188-1196 (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]. 
 
LPA is found in all cell types in small quantities (associated with membrane
biosynthesis) but is produced in significant quantities by some cellular
sources, accounting for the levels of LPA in serum. LPA is also found in
elevated levels in ovarian cancer ascites, and acts to stimulate
proliferation and promote survival of the cancer cells [8]. The effects of
LPA on the proliferation and morphology of a number of other cell types have
been well documented [6,8]. However, identification of the mechanisms by
which these effects are accomplished has been complicated by a number of
factors, such as: a lack of antagonists, difficulty in ligand-binding
experiments and the responsiveness of many cell types to LPA [8]. The
G protein-coupled receptors EDG-2, EDG-4 and EDG-7 have now been identified
as high affinity receptors for LPA. It has been suggested that these
receptors should now be referred to as lpA1, lpA2 and lpA3 respectively
[6,7].
 
LPARECEPTOR is a 6-element fingerprint that provides a signature for the
lysophosphatidic acid receptor family. The fingerprint was derived from an
initial alignment of 6 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 lysophosphatidic acid receptors
but distinguish them from the rest of the rhodopsin-like superfamily -
motifs 1 and 2 reside at the N-terminus; motif 3 spans the second
cytoplasmic loop; motif 4 lies in the third cytoplasmic loop; motif 5 spans
the third external loop; and motif 6 resides at the C-terminus. Two
iterations on SPTR39_15f were required to reach convergence, at which point
a true set comprising 12 sequences was identified.
Summary Information
12 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
6121212121212
5000000
4000000
3000000
2000000
123456
True Positives
EDG2_BOVIN    EDG2_HUMAN    EDG2_MOUSE    EDG2_SHEEP    
O00543 O43431 O88584 Q9JL06
Q9NRB8 Q9PU16 Q9PU17 Q9UBY5
Sequence Titles
EDG2_BOVIN  Lysophosphatidic acid receptor Edg-2 (LPA receptor 1) (LPA-1) (Rec1.3) - Bos taurus (Bovine). 
EDG2_HUMAN Lysophosphatidic acid receptor Edg-2 (LPA receptor 1) (LPA-1) - Homo sapiens (Human).
EDG2_MOUSE Lysophosphatidic acid receptor Edg-2 (LPA receptor 1) (LPA-1) (Rec1.3) (VZG-1) - Mus musculus (Mouse).
EDG2_SHEEP Lysophosphatidic acid receptor Edg-2 (LPA receptor 1) (LPA-1) - Ovis aries (Sheep).
O00543 R33799_1 (LYSOPHOSPHATIDIC ACID G PROTEIN-COUPLED RECEPTOR 4) - Homo sapiens (Human).
O43431 G PROTEIN-COUPLED RECEPTOR EDG-4 - Homo sapiens (Human).
O88584 LYSOPHOSPHATIDIC ACID RECEPTOR - Mus musculus (Mouse).
Q9JL06 LYSOPHOSPHATIDIC ACID RECEPTOR LPA2 - Mus musculus (Mouse).
Q9NRB8 G-PROTEIN COUPLED RECEPTOR EDG-7 - Homo sapiens (Human).
Q9PU16 LYSOPHOSPHATIDIC ACID RECEPTOR - Xenopus laevis (African clawed frog).
Q9PU17 LYSOPHOSPHATIDIC ACID RECEPTOR - Xenopus laevis (African clawed frog).
Q9UBY5 CALCIUM-MOBILIZING LYSOPHOSPHATIDIC ACID RECEPTOR LP-A3/EDG-7 - Homo sapiens (Human).
Scan History
SPTR39_15f 2  180  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
CYYNETIAFF Q9PU17 26 26 -
CYYNETIGFF O00543 7 7 -
CYYNETIGFF O43431 7 7 -
CHYDKHMDFF Q9NRB8 4 4 -
CHYDKHMDFF Q9UBY5 4 4 -

Motif 2 width=10
Element Seqn Id St Int Rpt
SGKYLATEWN Q9PU17 39 3 -
SGKELSSHWR O00543 20 3 -
SGKELSSHWR O43431 20 3 -
SNTDTVDDWT Q9NRB8 17 3 -
SNTDTVDDWT Q9UBY5 17 3 -

Motif 3 width=13
Element Seqn Id St Int Rpt
FRMQLHTRMSNRR Q9PU17 153 104 -
MAVQLHSRLPRGR O00543 134 104 -
MAVQLHSRLPRGR O43431 134 104 -
MRMRVHSNLTKKR Q9NRB8 132 105 -
MRMRVHSNLTKKR Q9UBY5 132 105 -

Motif 4 width=13
Element Seqn Id St Int Rpt
RQKTMRMSRHSSG Q9PU17 235 69 -
RRRVQRMAEHVSC O00543 216 69 -
RRRVQRMAEHVSC O43431 216 69 -
KRKTNVLSPHTSG Q9NRB8 214 69 -
KRKTNVLSPHTSG Q9UBY5 214 69 -

Motif 5 width=11
Element Seqn Id St Int Rpt
ICCPQCNILAY Q9PU17 284 36 -
LGCESCNVLAV O00543 266 37 -
LGCESCNVLAV O43431 266 37 -
LNCTQCGVQHV Q9NRB8 264 37 -
LNCRQCGVQHV Q9UBY5 264 37 -

Motif 6 width=12
Element Seqn Id St Int Rpt
TFKQILCCQRTE Q9PU17 323 28 -
TFRRLLCCACLR O00543 305 28 -
TFRRLLCCACLR O43431 305 28 -
TMKKMICCFSQE Q9NRB8 303 28 -
TMKKMICCFSQE Q9UBY5 303 28 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
CFYNESIAFF EDG2_SHEEP 24 24 -
CFYNESIAFF EDG2_MOUSE 24 24 -
CFYNESIAFF O88584 24 24 -
CFYNESIAFF EDG2_HUMAN 24 24 -
CFSNESIAFF EDG2_BOVIN 24 24 -
CYYNETIAFF Q9PU16 26 26 -
CYYNETIAFF Q9PU17 26 26 -
CYYNETIGFF O00543 7 7 -
CYYNETIGFF O43431 7 7 -
CYYNETIGFF Q9JL06 4 4 -
CHYDKHMDFF Q9NRB8 4 4 -
CHYDKHMDFF Q9UBY5 4 4 -

Motif 2 width=10
Element Seqn Id St Int Rpt
SGKYLATEWN EDG2_SHEEP 37 3 -
SGKYLATEWN EDG2_MOUSE 37 3 -
SGKYLATEWN O88584 37 3 -
SGKHLATEWN EDG2_HUMAN 37 3 -
SGKYLATEWN EDG2_BOVIN 37 3 -
SGKYLDTEWN Q9PU16 39 3 -
SGKYLATEWN Q9PU17 39 3 -
SGKELSSHWR O00543 20 3 -
SGKELSSHWR O43431 20 3 -
SGKELSLHWR Q9JL06 17 3 -
SNTDTVDDWT Q9NRB8 17 3 -
SNTDTVDDWT Q9UBY5 17 3 -

Motif 3 width=13
Element Seqn Id St Int Rpt
FRMQLHTRMSNRR EDG2_SHEEP 151 104 -
FRMQLHTRMSNRR EDG2_MOUSE 151 104 -
FRMQLHTRMSNRR O88584 151 104 -
FRMQLHTRMSNRR EDG2_HUMAN 151 104 -
FRMQLHARMSNRR EDG2_BOVIN 151 104 -
FRMQLHTRMSNRR Q9PU16 153 104 -
FRMQLHTRMSNRR Q9PU17 153 104 -
MAVQLHSRLPRGR O00543 134 104 -
MAVQLHSRLPRGR O43431 134 104 -
MAVQLHSRLPRGR Q9JL06 131 104 -
MRMRVHSNLTKKR Q9NRB8 132 105 -
MRMRVHSNLTKKR Q9UBY5 132 105 -

Motif 4 width=13
Element Seqn Id St Int Rpt
RQRTMRMSRHSSG EDG2_SHEEP 233 69 -
RQRTMRMSRHSSG EDG2_MOUSE 233 69 -
RQRTMRMSRHSSG O88584 233 69 -
RQRTMRMSRHSSG EDG2_HUMAN 233 69 -
RQRTMRMSRHSSG EDG2_BOVIN 233 69 -
RQRTMRMSRHSSG Q9PU16 235 69 -
RQKTMRMSRHSSG Q9PU17 235 69 -
RRRVQRMAEHVSC O00543 216 69 -
RRRVQRMAEHVSC O43431 216 69 -
RRRVERMAEHVSC Q9JL06 213 69 -
KRKTNVLSPHTSG Q9NRB8 214 69 -
KRKTNVLSPHTSG Q9UBY5 214 69 -

Motif 5 width=11
Element Seqn Id St Int Rpt
VCCPQCDVLAY EDG2_SHEEP 282 36 -
VCCPQCDVLAY EDG2_MOUSE 282 36 -
VCCPQCDVLAY O88584 282 36 -
VCCPQCDVLAY EDG2_HUMAN 282 36 -
VCCPQCDVLAY EDG2_BOVIN 282 36 -
VCCPQCNILAY Q9PU16 284 36 -
ICCPQCNILAY Q9PU17 284 36 -
LGCESCNVLAV O00543 266 37 -
LGCESCNVLAV O43431 266 37 -
LDCKTCNVLAV Q9JL06 263 37 -
LNCTQCGVQHV Q9NRB8 264 37 -
LNCRQCGVQHV Q9UBY5 264 37 -

Motif 6 width=12
Element Seqn Id St Int Rpt
TFRQILCCQRSE EDG2_SHEEP 321 28 -
TFRQILCCQRNE EDG2_MOUSE 321 28 -
TFRQILCCQRNE O88584 321 28 -
TFRQILCCQRSE EDG2_HUMAN 321 28 -
TFRQILCCQRSE EDG2_BOVIN 321 28 -
TFKQILCCQRTE Q9PU16 323 28 -
TFKQILCCQRTE Q9PU17 323 28 -
TFRRLLCCACLR O00543 305 28 -
TFRRLLCCACLR O43431 305 28 -
TFRRLLCCMCLR Q9JL06 302 28 -
TMKKMICCFSQE Q9NRB8 303 28 -
TMKKMICCFSQE Q9UBY5 303 28 -