WORKLIST ENTRIES (1):

OGR1RECEPTOR View alignment View Structure    OGR1 sphingosylphosphorylcholine receptor signature
 Type of fingerprint: COMPOUND with 11 elements
Links:
   PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
   PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
   PRINTS; PR00251 BACTRLOPSIN
   PRINTS; PR01563 G2ARECEPTOR; PR01147 GPR4RECEPTOR

 Creation date 17-AUG-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. XU, Y., ZHU, K., HONG, G., WU, W., BAUDHUIN, L.M., XIAO, Y. AND 
   DAMRON, D.S.
   Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled
   receptor 1.
   NAT.CELL BIOL. 2(5) 261-267 (2000).

   9. XU, Y. AND CASEY, G.
   Identification of human OGR1, a novel G protein-coupled receptor that maps
   to chromosome 14.
   GENOMICS 35(2) 397-402 (1996).

   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]. 
   
   SPC is produced from degradation of sphingomyelin and regulates many diverse
   cellular functions, such as: proliferation, growth inhibition, smooth muscle
   contraction and wound healing [6,8]. It is also thought to play a role in
   the cardiovascular system and potently activates inwardly rectifying K+
   channels, suggesting a possible role in regulation of heart rate [6].
   
   The orphan receptor OGR1 has been identified as a high affinity receptor for
   SPC [8]. OGR1 is expressed in ovarian cancer cell lines and also in spleen,
   testis, small intestine, peripheral blood leukocytes, brain, heart, lung,
   placenta and kidney. Expression has not been found in thymus, prostate,
   ovary, colon, liver, skeletal muscle or pancreas [9]. Upon activation by
   SPC, OGR1 couples to both Gi proteins, causing increases in intracellular 
   calcium, and Gq proteins, to activate MAP kinases, inhibiting proliferation.
   SPC also causes regulation of ion channel activity, binding of activator
   protein-1 to DNA, and expression of cell adhesion molecule-1 and 
   interleukin-6 [8].
  
   OGR1RECEPTOR is an 11-element fingerprint that provides a signature for the
   OGR1 sphingosylphosphorylcholine receptors. The fingerprint was derived from
   an initial alignment of 2 sequences: the motifs were drawn from conserved
   regions spanning virtually the full alignment length, focusing on those
   sections that characterise the OGR1 receptors but distinguish them from the 
   rest of the lysophospholipid receptor family - motif 1 resides at the 
   N-terminus; motif 2 spans part of the N-terminus, leading into TM domain 1; 
   motif 3 lies in the first external loop, leading into TM domain 3; motif 4 
   spans the second cytoplasmic loop; motif 5 encodes the C-terminal portion of
   TM domain 4, leading into the second external loop; motif 6 spans the third
   cytoplasmic loop; motif 7 encodes the third external loop; motif 8 lies at
   the C-terminus of TM domain 7; and motifs 9-11 reside at the C-terminus. A
   single iteration on SPTR39.22_17.3f was required to reach convergence, no 
   further sequences being identified beyond the starting set.

  SUMMARY INFORMATION
      2 codes involving 11 elements
      0 codes involving 10 elements
      0 codes involving  9 elements
      0 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 FINGERPRINT INDEX
  
   11|   2    2    2    2    2    2    2    2    2    2    2  
   10|   0    0    0    0    0    0    0    0    0    0    0  
    9|   0    0    0    0    0    0    0    0    0    0    0  
    8|   0    0    0    0    0    0    0    0    0    0    0  
    7|   0    0    0    0    0    0    0    0    0    0    0  
    6|   0    0    0    0    0    0    0    0    0    0    0  
    5|   0    0    0    0    0    0    0    0    0    0    0  
    4|   0    0    0    0    0    0    0    0    0    0    0  
    3|   0    0    0    0    0    0    0    0    0    0    0  
    2|   0    0    0    0    0    0    0    0    0    0    0  
   --+--------------------------------------------------------
     |   1    2    3    4    5    6    7    8    9   10   11  

True positives..
 GP68_HUMAN     O46685         


  PROTEIN TITLES
   GP68_HUMAN       PROBABLE G PROTEIN-COUPLED RECEPTOR GPR68 (OVARIAN CANCER G 
   O46685           ORPHAN G PROTEIN-COUPLED RECEPTOR BRGR1B - Bos taurus (Bovin

SCAN HISTORY SPTR39.22_17.3f 1 50 NSINGLE INITIAL MOTIF SETS OGR1RECEPTOR1 Length of motif = 16 Motif number = 1 OGR1 sphingosylphosphorylcholine receptor motif I - 1 PCODE ST INT MGNITADNSSMSCTID GP68_HUMAN 1 1 MGNITADNTSMNCDID O46685 1 1 OGR1RECEPTOR2 Length of motif = 14 Motif number = 2 OGR1 sphingosylphosphorylcholine receptor motif II - 1 PCODE ST INT DHTIHQTLAPVVYV GP68_HUMAN 16 -1 DHTIHQTLAPVVYV O46685 16 -1 OGR1RECEPTOR3 Length of motif = 13 Motif number = 3 OGR1 sphingosylphosphorylcholine receptor motif III - 1 PCODE ST INT DLSCQVCGILLYE GP68_HUMAN 91 61 DLSCQVCGILLYE O46685 91 61 OGR1RECEPTOR4 Length of motif = 12 Motif number = 4 OGR1 sphingosylphosphorylcholine receptor motif IV - 1 PCODE ST INT FRFHQFRTLKAA GP68_HUMAN 127 23 FRFHQFRTLKAA O46685 127 23 OGR1RECEPTOR5 Length of motif = 18 Motif number = 5 OGR1 sphingosylphosphorylcholine receptor motif V - 1 PCODE ST INT KELLTSIYFLMHEEVIED GP68_HUMAN 148 9 KELLTSIYFLMHEEVVED O46685 148 9 OGR1RECEPTOR6 Length of motif = 14 Motif number = 6 OGR1 sphingosylphosphorylcholine receptor motif VI - 1 PCODE ST INT RSHGTQKSRKDQIQ GP68_HUMAN 214 48 RSHGTQKSRKDQIQ O46685 214 48 OGR1RECEPTOR7 Length of motif = 14 Motif number = 7 OGR1 sphingosylphosphorylcholine receptor motif VII - 1 PCODE ST INT SVWEASCDFAKGVF GP68_HUMAN 252 24 SLWESSCDFAKGIF O46685 252 24 OGR1RECEPTOR8 Length of motif = 10 Motif number = 8 OGR1 sphingosylphosphorylcholine receptor motif VIII - 1 PCODE ST INT FVSETTHRDL GP68_HUMAN 288 22 FVSETTHRDL O46685 288 22 OGR1RECEPTOR9 Length of motif = 17 Motif number = 9 OGR1 sphingosylphosphorylcholine receptor motif IX - 1 PCODE ST INT LRGACLAFLTCSRTGRA GP68_HUMAN 300 2 LRGACLAFLTCARTGRA O46685 300 2 OGR1RECEPTOR10 Length of motif = 15 Motif number = 10 OGR1 sphingosylphosphorylcholine receptor motif X - 1 PCODE ST INT REAYPLGAPEASGKS GP68_HUMAN 317 0 REAYPLGAPEASGKS O46685 317 0 OGR1RECEPTOR11 Length of motif = 16 Motif number = 11 OGR1 sphingosylphosphorylcholine receptor motif XI - 1 PCODE ST INT EEPELLTKLHPAFQTP GP68_HUMAN 336 4 EDPEVLTRLHPAFQTP O46685 332 0 FINAL MOTIF SETS OGR1RECEPTOR1 Length of motif = 16 Motif number = 1 OGR1 sphingosylphosphorylcholine receptor motif I - 1 PCODE ST INT MGNITADNSSMSCTID GP68_HUMAN 1 1 MGNITADNTSMNCDID O46685 1 1 OGR1RECEPTOR2 Length of motif = 14 Motif number = 2 OGR1 sphingosylphosphorylcholine receptor motif II - 1 PCODE ST INT DHTIHQTLAPVVYV GP68_HUMAN 16 -1 DHTIHQTLAPVVYV O46685 16 -1 OGR1RECEPTOR3 Length of motif = 13 Motif number = 3 OGR1 sphingosylphosphorylcholine receptor motif III - 1 PCODE ST INT DLSCQVCGILLYE GP68_HUMAN 91 61 DLSCQVCGILLYE O46685 91 61 OGR1RECEPTOR4 Length of motif = 12 Motif number = 4 OGR1 sphingosylphosphorylcholine receptor motif IV - 1 PCODE ST INT FRFHQFRTLKAA GP68_HUMAN 127 23 FRFHQFRTLKAA O46685 127 23 OGR1RECEPTOR5 Length of motif = 18 Motif number = 5 OGR1 sphingosylphosphorylcholine receptor motif V - 1 PCODE ST INT KELLTSIYFLMHEEVIED GP68_HUMAN 148 9 KELLTSIYFLMHEEVVED O46685 148 9 OGR1RECEPTOR6 Length of motif = 14 Motif number = 6 OGR1 sphingosylphosphorylcholine receptor motif VI - 1 PCODE ST INT RSHGTQKSRKDQIQ GP68_HUMAN 214 48 RSHGTQKSRKDQIQ O46685 214 48 OGR1RECEPTOR7 Length of motif = 14 Motif number = 7 OGR1 sphingosylphosphorylcholine receptor motif VII - 1 PCODE ST INT SVWEASCDFAKGVF GP68_HUMAN 252 24 SLWESSCDFAKGIF O46685 252 24 OGR1RECEPTOR8 Length of motif = 10 Motif number = 8 OGR1 sphingosylphosphorylcholine receptor motif VIII - 1 PCODE ST INT FVSETTHRDL GP68_HUMAN 288 22 FVSETTHRDL O46685 288 22 OGR1RECEPTOR9 Length of motif = 17 Motif number = 9 OGR1 sphingosylphosphorylcholine receptor motif IX - 1 PCODE ST INT LRGACLAFLTCSRTGRA GP68_HUMAN 300 2 LRGACLAFLTCARTGRA O46685 300 2 OGR1RECEPTOR10 Length of motif = 15 Motif number = 10 OGR1 sphingosylphosphorylcholine receptor motif X - 1 PCODE ST INT REAYPLGAPEASGKS GP68_HUMAN 317 0 REAYPLGAPEASGKS O46685 317 0 OGR1RECEPTOR11 Length of motif = 16 Motif number = 11 OGR1 sphingosylphosphorylcholine receptor motif XI - 1 PCODE ST INT EEPELLTKLHPAFQTP GP68_HUMAN 336 4 EDPEVLTRLHPAFQTP O46685 332 0

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