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PR01564

Identifier
OGR1RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01564
No. of Motifs
11
Creation Date
17-AUG-2001
Title
OGR1 sphingosylphosphorylcholine receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
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. 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).

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]. 
 
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 Feature Index
1122222222222
1000000000000
900000000000
800000000000
700000000000
600000000000
500000000000
400000000000
300000000000
200000000000
1234567891011
True Positives
O46685        OGR1_HUMAN    
Sequence Titles
O46685      ORPHAN G PROTEIN-COUPLED RECEPTOR BRGR1B - Bos taurus (Bovine). 
OGR1_HUMAN PROBABLE G PROTEIN-COUPLED RECEPTOR OGR1 - HOMO SAPIENS (HUMAN).
Scan History
SPTR39.22_17.3f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
MGNITADNSSMSCTID OGR1_HUMAN 1 1 -
MGNITADNTSMNCDID O46685 1 1 -

Motif 2 width=14
Element Seqn Id St Int Rpt
DHTIHQTLAPVVYV OGR1_HUMAN 16 -1 -
DHTIHQTLAPVVYV O46685 16 -1 -

Motif 3 width=13
Element Seqn Id St Int Rpt
DLSCQVCGILLYE OGR1_HUMAN 91 61 -
DLSCQVCGILLYE O46685 91 61 -

Motif 4 width=12
Element Seqn Id St Int Rpt
FRFHQFRTLKAA OGR1_HUMAN 127 23 -
FRFHQFRTLKAA O46685 127 23 -

Motif 5 width=18
Element Seqn Id St Int Rpt
KELLTSIYFLMHEEVIED OGR1_HUMAN 148 9 -
KELLTSIYFLMHEEVVED O46685 148 9 -

Motif 6 width=14
Element Seqn Id St Int Rpt
RSHGTQKSRKDQIQ OGR1_HUMAN 214 48 -
RSHGTQKSRKDQIQ O46685 214 48 -

Motif 7 width=14
Element Seqn Id St Int Rpt
SVWEASCDFAKGVF OGR1_HUMAN 252 24 -
SLWESSCDFAKGIF O46685 252 24 -

Motif 8 width=10
Element Seqn Id St Int Rpt
FVSETTHRDL OGR1_HUMAN 288 22 -
FVSETTHRDL O46685 288 22 -

Motif 9 width=17
Element Seqn Id St Int Rpt
LRGACLAFLTCSRTGRA OGR1_HUMAN 300 2 -
LRGACLAFLTCARTGRA O46685 300 2 -

Motif 10 width=15
Element Seqn Id St Int Rpt
REAYPLGAPEASGKS OGR1_HUMAN 317 0 -
REAYPLGAPEASGKS O46685 317 0 -

Motif 11 width=16
Element Seqn Id St Int Rpt
EEPELLTKLHPAFQTP OGR1_HUMAN 336 4 -
EDPEVLTRLHPAFQTP O46685 332 0 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
MGNITADNSSMSCTID OGR1_HUMAN 1 1 -
MGNITADNTSMNCDID O46685 1 1 -

Motif 2 width=14
Element Seqn Id St Int Rpt
DHTIHQTLAPVVYV OGR1_HUMAN 16 -1 -
DHTIHQTLAPVVYV O46685 16 -1 -

Motif 3 width=13
Element Seqn Id St Int Rpt
DLSCQVCGILLYE OGR1_HUMAN 91 61 -
DLSCQVCGILLYE O46685 91 61 -

Motif 4 width=12
Element Seqn Id St Int Rpt
FRFHQFRTLKAA OGR1_HUMAN 127 23 -
FRFHQFRTLKAA O46685 127 23 -

Motif 5 width=18
Element Seqn Id St Int Rpt
KELLTSIYFLMHEEVIED OGR1_HUMAN 148 9 -
KELLTSIYFLMHEEVVED O46685 148 9 -

Motif 6 width=14
Element Seqn Id St Int Rpt
RSHGTQKSRKDQIQ OGR1_HUMAN 214 48 -
RSHGTQKSRKDQIQ O46685 214 48 -

Motif 7 width=14
Element Seqn Id St Int Rpt
SVWEASCDFAKGVF OGR1_HUMAN 252 24 -
SLWESSCDFAKGIF O46685 252 24 -

Motif 8 width=10
Element Seqn Id St Int Rpt
FVSETTHRDL OGR1_HUMAN 288 22 -
FVSETTHRDL O46685 288 22 -

Motif 9 width=17
Element Seqn Id St Int Rpt
LRGACLAFLTCSRTGRA OGR1_HUMAN 300 2 -
LRGACLAFLTCARTGRA O46685 300 2 -

Motif 10 width=15
Element Seqn Id St Int Rpt
REAYPLGAPEASGKS OGR1_HUMAN 317 0 -
REAYPLGAPEASGKS O46685 317 0 -

Motif 11 width=16
Element Seqn Id St Int Rpt
EEPELLTKLHPAFQTP OGR1_HUMAN 336 4 -
EDPEVLTRLHPAFQTP O46685 332 0 -