WORKLIST ENTRIES (1):
LPARECEPTOR View alignment View Structure Lysophosphatidic acid receptor family signature
Type of fingerprint: COMPOUND with 6 elements
Links:
PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
PRINTS; PR00251 BACTRLOPSIN
PRINTS; PR01148 EDG2RECEPTOR; PR01528 EDG4RECEPTOR; PR01560 EDG7RECEPTOR
Creation date 21-MAY-2001
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).
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 [1,2]. 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 lysophospholipid 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 FINGERPRINT INDEX
6| 12 12 12 12 12 12
5| 0 0 0 0 0 0
4| 0 0 0 0 0 0
3| 0 0 0 0 0 0
2| 0 0 0 0 0 0
--+-------------------------------
| 1 2 3 4 5 6
True positives..
EDG2_SHEEP EDG2_MOUSE O88584 EDG2_HUMAN
EDG2_BOVIN Q9PU16 Q9PU17 O00543
O43431 Q9JL06 Q9UBY5 Q9NRB8
PROTEIN TITLES
EDG2_SHEEP LYSOPHOSPHATIDIC ACID RECEPTOR (EDG-2) - Ovis aries (Sheep).
EDG2_MOUSE LYSOPHOSPHATIDIC ACID RECEPTOR (EDG-2) (REC1.3) (VZG-1) - Mu
O88584 LYSOPHOSPHATIDIC ACID RECEPTOR - Mus musculus (Mouse).
EDG2_HUMAN LYSOPHOSPHATIDIC ACID RECEPTOR (EDG-2) - Homo sapiens (Human
EDG2_BOVIN LYSOPHOSPHATIDIC ACID RECEPTOR (EDG-2) (REC1.3) - Bos taurus
Q9PU16 LYSOPHOSPHATIDIC ACID RECEPTOR - Xenopus laevis (African cla
Q9PU17 LYSOPHOSPHATIDIC ACID RECEPTOR - Xenopus laevis (African cla
O00543 R33799_1 (LYSOPHOSPHATIDIC ACID G PROTEIN-COUPLED RECEPTOR 4
O43431 G PROTEIN-COUPLED RECEPTOR EDG-4 - Homo sapiens (Human).
Q9JL06 LYSOPHOSPHATIDIC ACID RECEPTOR LPA2 - Mus musculus (Mouse).
Q9UBY5 CALCIUM-MOBILIZING LYSOPHOSPHATIDIC ACID RECEPTOR LP-A3/EDG-
Q9NRB8 G protein COUPLED RECEPTOR EDG-7 - Homo sapiens (Human).
SCAN HISTORY
SPTR39_15f 2 180 NSINGLE
INITIAL MOTIF SETS
LPARECEPTOR1 Length of motif = 10 Motif number = 1
Lysophosphatidic acid receptor family motif I - 1
PCODE ST INT
CYYNETIGFF O00543 7 7
CYYNETIGFF O43431 7 7
CYYNETIAFF Q9PU17 26 26
CHYDKHMDFF Q9NRB8 4 4
CHYDKHMDFF Q9UBY5 4 4
LPARECEPTOR2 Length of motif = 10 Motif number = 2
Lysophosphatidic acid receptor family motif II - 1
PCODE ST INT
SGKELSSHWR O00543 20 3
SGKELSSHWR O43431 20 3
SGKYLATEWN Q9PU17 39 3
SNTDTVDDWT Q9NRB8 17 3
SNTDTVDDWT Q9UBY5 17 3
LPARECEPTOR3 Length of motif = 13 Motif number = 3
Lysophosphatidic acid receptor family motif III - 1
PCODE ST INT
MAVQLHSRLPRGR O00543 134 104
MAVQLHSRLPRGR O43431 134 104
FRMQLHTRMSNRR Q9PU17 153 104
MRMRVHSNLTKKR Q9NRB8 132 105
MRMRVHSNLTKKR Q9UBY5 132 105
LPARECEPTOR4 Length of motif = 13 Motif number = 4
Lysophosphatidic acid receptor family motif IV - 1
PCODE ST INT
RRRVQRMAEHVSC O00543 216 69
RRRVQRMAEHVSC O43431 216 69
RQKTMRMSRHSSG Q9PU17 235 69
KRKTNVLSPHTSG Q9NRB8 214 69
KRKTNVLSPHTSG Q9UBY5 214 69
LPARECEPTOR5 Length of motif = 11 Motif number = 5
Lysophosphatidic acid receptor family motif V - 1
PCODE ST INT
LGCESCNVLAV O00543 266 37
LGCESCNVLAV O43431 266 37
ICCPQCNILAY Q9PU17 284 36
LNCTQCGVQHV Q9NRB8 264 37
LNCRQCGVQHV Q9UBY5 264 37
LPARECEPTOR6 Length of motif = 12 Motif number = 6
Lysophosphatidic acid receptor family motif VI - 1
PCODE ST INT
TFRRLLCCACLR O00543 305 28
TFRRLLCCACLR O43431 305 28
TFKQILCCQRTE Q9PU17 323 28
TMKKMICCFSQE Q9NRB8 303 28
TMKKMICCFSQE Q9UBY5 303 28
FINAL MOTIF SETS
LPARECEPTOR1 Length of motif = 10 Motif number = 1
Lysophosphatidic acid receptor family motif I - 2
PCODE ST INT
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
LPARECEPTOR2 Length of motif = 10 Motif number = 2
Lysophosphatidic acid receptor family motif II - 2
PCODE ST INT
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
LPARECEPTOR3 Length of motif = 13 Motif number = 3
Lysophosphatidic acid receptor family motif III - 2
PCODE ST INT
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
LPARECEPTOR4 Length of motif = 13 Motif number = 4
Lysophosphatidic acid receptor family motif IV - 2
PCODE ST INT
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
LPARECEPTOR5 Length of motif = 11 Motif number = 5
Lysophosphatidic acid receptor family motif V - 2
PCODE ST INT
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
LPARECEPTOR6 Length of motif = 12 Motif number = 6
Lysophosphatidic acid receptor family motif VI - 2
PCODE ST INT
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
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