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PR00586

Identifier
PRSTNOIDEP4R  [View Relations]  [View Alignment]  
Accession
PR00586
No. of Motifs
8
Creation Date
25-SEP-1996  (UPDATE 07-JUN-1999)
Title
Prostanoid EP4 receptor signature 
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01788 PROSTANOIDR; PR00428 PROSTAGLNDNR
INTERPRO; IPR001758
GCRDB; GCR_0889; GCR_0718
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. 
 
EP4 receptors are found in high levels in the intestine, and in lower
levels in the lung, kidney, thymus, uterus and brain; they are not found in
the liver, heart, retina or in skeletal muscle. The receptors activate
adenylate cyclase.
 
PRSTNOIDEP4R is an 8-element fingerprint that provides a signature for the
prostanoid EP4 receptors. The fingerprint was derived from an initial
alignment of 5 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 EP4 receptors but distinguish
them from the rest of the rhodopsin-like superfamily - motif 1 lies at the
N-terminus; motif 2 spans the first cytoplasmic loop; motif 3 spans the
first external loop; motif 4 lies in the second cytoplasmic loop; motif 5
lies in the second external loop; motifs 6 and 7 span the third cytoplasmic
loop; and motif 8 lies at the C-terminus. A single iteration on OWL28.0 was
required to reach convergence, no further sequences being identified beyond
the starting set.
 
An update on SPTR37_9f identified a true set of 4 sequences.
Summary Information
4 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
844444444
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
PE24_HUMAN    PE24_MOUSE    PE24_RABIT    PE24_RAT      
Sequence Titles
PE24_HUMAN  Prostaglandin E2 receptor, EP4 subtype (Prostanoid EP4 receptor) (PGE receptor, EP4 subtype) - Homo sapiens (Human). 
PE24_MOUSE Prostaglandin E2 receptor, EP4 subtype (Prostanoid EP4 receptor) (PGE receptor, EP4 subtype) - Mus musculus (Mouse).
PE24_RABIT Prostaglandin E2 receptor, EP4 subtype (Prostanoid EP4 receptor) (PGE receptor, subtype EP4) - Oryctolagus cuniculus (Rabbit).
PE24_RAT Prostaglandin E2 receptor, EP4 subtype (Prostanoid EP4 receptor) (PGE receptor, EP4 subtype) - Rattus norvegicus (Rat).
Scan History
OWL28_0    1  100  NSINGLE    
SPTR37_9f 2 5 NSINGLE
Initial Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
SIPGVNASFSSTPERLNSPVT PER4_MOUSE 27 27 -
SIPGVNASFSSTPERLNSPVT PER4_RAT 2 2 -
STPGVNSSASLSPDRLNSPVT PER4_HUMAN 2 2 -
STPGVNSSASLSPDRLNSPVT HUMPGE2R 2 2 -
STPVANASASSMPELLNNPVT RABEP4R 2 2 -

Motif 2 width=18
Element Seqn Id St Int Rpt
CKSRKEQKETTFYTLVCG PER4_MOUSE 68 20 -
CKSRKEQKETTFYTLVCG PER4_RAT 43 20 -
CKSRKEQKETTFYTLVCG PER4_HUMAN 43 20 -
CKSRKEQKETTFYTLVCG HUMPGE2R 43 20 -
CKSRKEQKETTFYTLVCG RABEP4R 43 20 -

Motif 3 width=22
Element Seqn Id St Int Rpt
MKGQWPGDQALCDYSTFILLFF PER4_MOUSE 106 20 -
MKGQWPGDQALCDYSTFILLFF PER4_RAT 81 20 -
MKGQWPGGQPLCEYSTFILLFF PER4_HUMAN 81 20 -
MKGQWPGGQPLCEYSTFILLFF HUMPGE2R 81 20 -
MKGQWPGGQALCDYSTFILLFF RABEP4R 81 20 -

Motif 4 width=18
Element Seqn Id St Int Rpt
NHAYFYSHYVDKRLAGLT PER4_MOUSE 147 19 -
NHAYFYSHYVDKRLAGLT PER4_RAT 122 19 -
NHAYFYSHYVDKRLAGLT PER4_HUMAN 122 19 -
NHAYFYSHYVDKRLAGLT HUMPGE2R 122 19 -
NHAYFYSHYVDKRLAGLT RABEP4R 122 19 -

Motif 5 width=21
Element Seqn Id St Int Rpt
FIDWTTNVTAYAAFSYMYAGF PER4_MOUSE 196 31 -
FIDWTTNVTAYAAFSYMYAGF PER4_RAT 171 31 -
FIDWTTNVTAHAAYSYMYAGF PER4_HUMAN 171 31 -
FIDWTTNVTAHAAYSYMYAGF HUMPGE2R 171 31 -
FIDWRTNVTAHAAFSYMYAGF RABEP4R 171 31 -

Motif 6 width=23
Element Seqn Id St Int Rpt
CGALLRMHRQFMRRTSLGTEQHH PER4_MOUSE 232 15 -
CGALLRMLRQFMRRTSLGTEQHH PER4_RAT 207 15 -
CGALLRMHRQFMRRTSLGTEQHH PER4_HUMAN 207 15 -
CGALLRMHRQFMRRTSLGTEQHH HUMPGE2R 207 15 -
CGALLRMHRQFMRRTSLGTEQHH RABEP4R 207 15 -

Motif 7 width=24
Element Seqn Id St Int Rpt
RGHAGASPALQRLSDFRRRRSFRR PER4_MOUSE 267 12 -
RGHAAASPALQRLSDFRRRRSFRR PER4_RAT 242 12 -
RGHPAASPALPRLSDFRRRRSFRR PER4_HUMAN 239 9 -
RGHPAASPALPRLSDFRRRRSFRR HUMPGE2R 239 9 -
RGHPTASPALPRLSDFRRRRSFRR RABEP4R 242 12 -

Motif 8 width=24
Element Seqn Id St Int Rpt
EKIKCLFCRIGGSGRDSSAQHCSE PER4_MOUSE 370 79 -
EKIKCLFCRIGGSGRDGSAQHCSE PER4_RAT 345 79 -
EKIKCLFCRIGGSRRERSGQHCSD PER4_HUMAN 342 79 -
EKIKCLFCRIGGSRRERSGQHCSD HUMPGE2R 342 79 -
EKIKCLFCRIGGSRRDRSGQHCSD RABEP4R 345 79 -
Final Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
SIPGVNASFSSTPERLNSPVT PE24_MOUSE 27 27 -
SIPGVNASFSSTPERLNSPVT PE24_RAT 2 2 -
STPVANASASSMPELLNNPVT PE24_RABIT 2 2 -
STPGVNSSASLSPDRLNSPVT PE24_HUMAN 2 2 -

Motif 2 width=18
Element Seqn Id St Int Rpt
CKSRKEQKETTFYTLVCG PE24_MOUSE 68 20 -
CKSRKEQKETTFYTLVCG PE24_RAT 43 20 -
CKSRKEQKETTFYTLVCG PE24_RABIT 43 20 -
CKSRKEQKETTFYTLVCG PE24_HUMAN 43 20 -

Motif 3 width=22
Element Seqn Id St Int Rpt
MKGQWPGDQALCDYSTFILLFF PE24_MOUSE 106 20 -
MKGQWPGDQALCDYSTFILLFF PE24_RAT 81 20 -
MKGQWPGGQALCDYSTFILLFF PE24_RABIT 81 20 -
MKGQWPGGQPLCEYSTFILLFF PE24_HUMAN 81 20 -

Motif 4 width=18
Element Seqn Id St Int Rpt
NHAYFYSHYVDKRLAGLT PE24_MOUSE 147 19 -
NHAYFYSHYVDKRLAGLT PE24_RAT 122 19 -
NHAYFYSHYVDKRLAGLT PE24_RABIT 122 19 -
NHAYFYSHYVDKRLAGLT PE24_HUMAN 122 19 -

Motif 5 width=21
Element Seqn Id St Int Rpt
FIDWTTNVTAYAAFSYMYAGF PE24_MOUSE 196 31 -
FIDWTTNVTAYAAFSYMYAGF PE24_RAT 171 31 -
FIDWRTNVTAHAAFSYMYAGF PE24_RABIT 171 31 -
FIDWTTNVTAHAAYSYMYAGF PE24_HUMAN 171 31 -

Motif 6 width=23
Element Seqn Id St Int Rpt
CGALLRMHRQFMRRTSLGTEQHH PE24_MOUSE 232 15 -
CGALLRMLRQFMRRTSLGTEQHH PE24_RAT 207 15 -
CGALLRMHRQFMRRTSLGTEQHH PE24_RABIT 207 15 -
CGALLRMHRQFMRRTSLGTEQHH PE24_HUMAN 207 15 -

Motif 7 width=24
Element Seqn Id St Int Rpt
RGHAGASPALQRLSDFRRRRSFRR PE24_MOUSE 267 12 -
RGHAAASPALQRLSDFRRRRSFRR PE24_RAT 242 12 -
RGHPTASPALPRLSDFRRRRSFRR PE24_RABIT 242 12 -
RGHPAASPALPRLSDFRRRRSFRR PE24_HUMAN 239 9 -

Motif 8 width=24
Element Seqn Id St Int Rpt
EKIKCLFCRIGGSGRDSSAQHCSE PE24_MOUSE 370 79 -
EKIKCLFCRIGGSGRDGSAQHCSE PE24_RAT 345 79 -
EKIKCLFCRIGGSRRDRSGQHCSD PE24_RABIT 345 79 -
EKIKCLFCRIGGSRRERSGQHCSD PE24_HUMAN 342 79 -