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PR00856

Identifier
PRSTNOIDIPR  [View Relations]  [View Alignment]  
Accession
PR00856
No. of Motifs
9
Creation Date
10-FEB-1998  (UPDATE 07-JUN-1999)
Title
Prostacyclin (prostanoid IP) receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01788 PROSTANOIDR; PR00428 PROSTAGLNDNR
INTERPRO; IPR000370
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. WATSON, S. AND ARKINSTALL,
Prostanoids.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp239-251.

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]. 
 
Prostanoids (prostaglandins (PG) and thromboxanes (TX)) mediate a wide
variety of actions and play important physiological roles in the cardio-
vascular and immune systems, and in pain sensation in peripheral systems
[6]. PGI2 and TXA2 have opposing actions, involving regulation of the
interaction of platelets with the vascular endothelium, while PGE2, PGI2
and PGD2 are powerful vasodilators and potentiate the action of various
autocoids to induce plasma extravasation and pain sensation. To date,
evidence for at least 5 classes of prostanoid receptor has been obtained.
However, identification of subtypes and their distribution is hampered by
expression of more than one receptor within a tissue, coupled with poor
selectivity of available agonists and antagonists. 
 
IP receptors induce relaxation in a range of smooth muscles, including
blood vessels, and potently inhibit platelet activation [6]. The receptors
activate adenylyl cyclase through Gs [6].
 
PRSTNOIDIPR is a 9-element fingerprint that provides a signature for the
prostacyclin (prostanoid IP) receptors. The fingerprint was derived from
an initial alignment of 4 sequences: the motifs were drawn from conserved
sections within either loop or N- and C-terminal regions, focusing on those
areas of the alignment that characterise the prostanoid IP receptors but 
distinguish them from the rest of the prostanoid receptor family - motif 1
lies at the N-terminus, leading into TM domain 1; motif 2 spans the first 
cytoplasmic loop, leading into TM domain 2; motif 3 spans the first external
loop; motif 4 spans the second cytoplasmic loop; motif 5 lies in the second
external loop; motif 6 lies in the third cytoplasmic loop, leading into
TM domain 6; motif 7 lies in the third external loop; and motifs 8 and 9
reside at the C-terminus. A single iteration on OWL29.6 was required to 
reach convergence, no further sequences being identified beyond the starting
set. A single partial match was found, PER2_HUMAN, a human prostanoid EP2
receptor subtype that matches motifs 2 and 5.
 
An update on SPTR37_9f identified a true set of 4 sequences.
Summary Information
4 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
9444444444
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
PI2R_BOVIN    PI2R_HUMAN    PI2R_MOUSE    PI2R_RAT      
Sequence Titles
PI2R_BOVIN  Prostacyclin receptor (Prostanoid IP receptor) (PGI receptor) (Prostaglandin I2 receptor) - Bos taurus (Bovine). 
PI2R_HUMAN Prostacyclin receptor (Prostanoid IP receptor) (PGI receptor) (Prostaglandin I2 receptor) - Homo sapiens (Human).
PI2R_MOUSE Prostacyclin receptor (Prostanoid IP receptor) (PGI receptor) (Prostaglandin I2 receptor) - Mus musculus (Mouse).
PI2R_RAT Prostacyclin receptor (Prostanoid IP receptor) (PGI receptor) (Prostaglandin I2 receptor) - Rattus norvegicus (Rat).
Scan History
OWL29_6    1  50   NSINGLE    
SPTR37_9f 2 5 NSINGLE
Initial Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
SCRNLTYVRDSVGPATSTLMF BTZ93039 4 4 -
SCWNITYVQDSVGPATSTLMF PI2R_RAT 33 33 -
SCWNITYVQDSVGPATSTLMF PI2R_MOUSE 32 32 -
SCRNLTYVRGSVGPATSTLMF PI2R_HUMAN 4 4 -

Motif 2 width=16
Element Seqn Id St Int Rpt
ARRRSHPSAFAVLVTG PI2R_MOUSE 68 15 -
ARRRSHPSAFAVLVTG PI2R_RAT 69 15 -
ARRHSRPSAFAVLVTG BTZ93039 40 15 -
ARRPARPSAFAVLVTG PI2R_HUMAN 40 15 -

Motif 3 width=16
Element Seqn Id St Int Rpt
ARNSSLLGLARGRPAL BTZ93039 76 20 -
ARNSSLLGLAHGGTML PI2R_RAT 105 20 -
ARNSSLLGLARGGPAL PI2R_HUMAN 76 20 -
ARNSSLLGLAHGGTML PI2R_MOUSE 104 20 -

Motif 4 width=17
Element Seqn Id St Int Rpt
LSHPYLYAQLDGPRCAR PI2R_MOUSE 149 29 -
LSHPYLYAQLDGPRRAR BTZ93039 121 29 -
LSHPYLYAQLDGPRCAR PI2R_RAT 150 29 -
LSHPYLYAQLDGPRCAR PI2R_HUMAN 121 29 -

Motif 5 width=17
Element Seqn Id St Int Rpt
CPGSWCFIRMRSAEPGG BTZ93039 165 27 -
CPGSWCFIRMRSAQPGG PI2R_MOUSE 193 27 -
CPGSWCFIRMRSPQPGG PI2R_RAT 194 27 -
CPGSWCFLRMRWAQPGG PI2R_HUMAN 165 27 -

Motif 6 width=16
Element Seqn Id St Int Rpt
PTSRAREDEVYHLILL PI2R_RAT 255 44 -
PRPRAGEDEVDHLILL BTZ93039 225 43 -
PRPRTGEDEVDHLILL PI2R_HUMAN 226 44 -
PTSRAREDEVYHLILL PI2R_MOUSE 254 44 -

Motif 7 width=13
Element Seqn Id St Int Rpt
IRGFTQAIAPDSS BTZ93039 258 17 -
IRGFTQAIAPDSR PI2R_MOUSE 285 15 -
IRGFTQAIAPDSR PI2R_RAT 286 15 -
IRCFTQAVAPDSS PI2R_HUMAN 257 15 -

Motif 8 width=19
Element Seqn Id St Int Rpt
KEGSCVPLSAWGEGQVEPL PI2R_HUMAN 342 72 -
KKGNWVPLSAWGEGQGGPL BTZ93039 342 71 -
KEGSWVPLSSWGTGQVAPL PI2R_MOUSE 369 71 -
KEGNWVPLSTWGTGQVAPL PI2R_RAT 370 71 -

Motif 9 width=15
Element Seqn Id St Int Rpt
VGMPSKSEAIAACSL PI2R_MOUSE 400 12 -
VGTSSKAEASVACSL PI2R_HUMAN 371 10 -
VGMPSKTEAVVACSL PI2R_RAT 401 12 -
VGTPSKAGSEAACSL BTZ93039 370 9 -
Final Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
SCWNITYVQDSVGPATSTLMF PI2R_MOUSE 32 32 -
SCWNITYVQDSVGPATSTLMF PI2R_RAT 33 33 -
SCRNLTYVRDSVGPATSTLMF PI2R_BOVIN 4 4 -
SCRNLTYVRGSVGPATSTLMF PI2R_HUMAN 4 4 -

Motif 2 width=16
Element Seqn Id St Int Rpt
ARRRSHPSAFAVLVTG PI2R_MOUSE 68 15 -
ARRRSHPSAFAVLVTG PI2R_RAT 69 15 -
ARRHSRPSAFAVLVTG PI2R_BOVIN 40 15 -
ARRPARPSAFAVLVTG PI2R_HUMAN 40 15 -

Motif 3 width=16
Element Seqn Id St Int Rpt
ARNSSLLGLAHGGTML PI2R_MOUSE 104 20 -
ARNSSLLGLAHGGTML PI2R_RAT 105 20 -
ARNSSLLGLARGRPAL PI2R_BOVIN 76 20 -
ARNSSLLGLARGGPAL PI2R_HUMAN 76 20 -

Motif 4 width=17
Element Seqn Id St Int Rpt
LSHPYLYAQLDGPRCAR PI2R_MOUSE 149 29 -
LSHPYLYAQLDGPRCAR PI2R_RAT 150 29 -
LSHPYLYAQLDGPRRAR PI2R_BOVIN 121 29 -
LSHPYLYAQLDGPRCAR PI2R_HUMAN 121 29 -

Motif 5 width=17
Element Seqn Id St Int Rpt
CPGSWCFIRMRSAQPGG PI2R_MOUSE 193 27 -
CPGSWCFIRMRSPQPGG PI2R_RAT 194 27 -
CPGSWCFIRMRSAEPGG PI2R_BOVIN 165 27 -
CPGSWCFLRMRWAQPGG PI2R_HUMAN 165 27 -

Motif 6 width=16
Element Seqn Id St Int Rpt
PTSRAREDEVYHLILL PI2R_MOUSE 254 44 -
PTSRAREDEVYHLILL PI2R_RAT 255 44 -
PRPRAGEDEVDHLILL PI2R_BOVIN 225 43 -
PRPRTGEDEVDHLILL PI2R_HUMAN 226 44 -

Motif 7 width=13
Element Seqn Id St Int Rpt
IRGFTQAIAPDSR PI2R_MOUSE 285 15 -
IRGFTQAIAPDSR PI2R_RAT 286 15 -
IRGFTQAIAPDSS PI2R_BOVIN 258 17 -
IRCFTQAVAPDSS PI2R_HUMAN 257 15 -

Motif 8 width=19
Element Seqn Id St Int Rpt
KEGSWVPLSSWGTGQVAPL PI2R_MOUSE 369 71 -
KEGNWVPLSTWGTGQVAPL PI2R_RAT 370 71 -
KKGNWVPLSAWGEGQGGPL PI2R_BOVIN 342 71 -
KEGSCVPLSAWGEGQVEPL PI2R_HUMAN 342 72 -

Motif 9 width=15
Element Seqn Id St Int Rpt
VGMPSKSEAIAACSL PI2R_MOUSE 400 12 -
VGMPSKTEAVVACSL PI2R_RAT 401 12 -
VGTPSKAGSEAACSL PI2R_BOVIN 370 9 -
VGTSSKAEASVACSL PI2R_HUMAN 371 10 -