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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