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PR01066

Identifier
P2Y4PRNOCPTR  [View Relations]  [View Alignment]  
Accession
PR01066; PR00596
No. of Motifs
9
Creation Date
31-JAN-1999  (UPDATE 29-NOV-2001)
Title
P2Y4 purinoceptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01157 P2YPURNOCPTR
INTERPRO; IPR000018
GCRDB; GCR_1952; GCR_2065; GCR_2085
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, S.
Adenosine and adenine nucleotides.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.19-31.
 
7. COMMUNI, D., JANSSENS, R., SUAREZ-HUERTA, N., ROBAYE, B. AND BOEYNAEMS, J.
Advances in signalling by extracellular nucleotides: the role and 
transduction mechanisms of P2Y receptors.
CELL SIGNAL. 12 351-360 (2000).
 
8. COMMUNI, D., PIROTTON, S., PARMENTIER, M. AND BOEYNAEMS, J.M.
Cloning and functional expression of a human uridine nucleotide receptor.
J.BIOL.CHEM. 270 30849-30852 (1995). 

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]. 
 
In addition to their roles in energy metabolism, extracellular nucleotides 
(such as ATP) can act as signalling molecules to induce a wide variety of 
biological effects. They are released into the extracellular fluid as a 
result of cell lysis, exocytosis of nucleotide-containing granules or by 
efflux through membrane transport proteins, and can function as autocrine 
and paracrine mediators [6,7]. Nucleotides play a role in synaptic 
transmission and in platelet-vessel wall interactions. In neurons of the 
central and peripheral nervous system, ATP is colocalised and cosecreted 
with more traditional neurotransmitters, such as catecholamines and 
acetylcholine, and has excitatory effects [6,7]. ATP is also found in high 
concentrations in the dense granules of platelets, together with ADP. These 
granules also contain lower levels of other nucleotides, such as adenine 
dinucleotides, GTP and UTP [7]. In addition, ADP is released from the 
vascular endothelium following injury and causes activation of platelets [6].
 
Receptors for adenine nucleotides are collectively termed P2 purinoceptors. 
They can be further subdivided into two structural classes: P2X receptors 
are ligand-gated ion channels, while P2Y receptors are G protein-coupled 
receptors. P2Y receptors have also been identified that are selective for 
uridine (rather than adenine) nucleotides [7]. 
 
A new subtype of P2 purinoceptors has been isolated [8]. Its deduced amino
acid sequence is consistent with a GPCR that is 51% identical to the human
P2Y2 receptor and 35% identical to the chick P2Y1 receptor [8]. P2Y4 is
expressed in the placenta, with low levels in the lung and vascular smooth
muscle. The receptor is activated by both UTP and ATP, UTP being more
potent in humans, both nucleotides having equal potency in rat. P2Y4
can couple to both Gi and Gq proteins to activate phospholipase C [7].
 
P2Y4PRNOCPTR is a 9-element fingerprint that provides a signature for the
P2Y4 purinoceptors. The fingerprint was derived from an initial alignment of 
3 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise the 
P2Y4 receptors but distinguish them from the rest of the P2Y receptor family 
- motif 1 resides at the N-terminus; motif 2 encodes the C-terminal portion
of TM domain 1 and the first cytoplasmic loop; motif 3 spans the second 
cytoplasmic loop; motif 4 lies in the second external loop; motif 5 encodes 
the third cytoplasmic loop; motif 6 lies in the third external loop; and 
motifs 7-9 span the C-terminal portion of TM domain 7 and the C-terminus.
A single iteration on SPTR40_18f was required to reach convergence, no 
further sequences being identified beyond the starting set.
 
An update on SPTR40_18f identified no further matches.
Summary Information
3 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
9333333333
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
O35811        P2Y4_HUMAN    Q9JJS7        
Sequence Titles
O35811      G-PROTEIN COUPLED RECEPTOR - Rattus norvegicus (Rat). 
P2Y4_HUMAN Uridine nucleotide receptor (UNR) (P2P) (P2Y4) - Homo sapiens (Human).
Q9JJS7 P2Y4 RECEPTOR - Mus musculus (Mouse).
Scan History
OWL31_1    1  50   NSINGLE    
SPTR37_9f 2 72 NSINGLE
SPTR40_18f 1 20 NSINGLE
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
ESLLFTSLGPSPSSG O35811 5 5 -
DSLLFTSLGPSPSSG Q9JJS7 5 5 -
ESSLLRSLGLSPGPG P2Y4_HUMAN 5 5 -

Motif 2 width=17
Element Seqn Id St Int Rpt
PTLWLFLFRLRPWDATA O35811 51 31 -
PTLWLFLFRLRPWDATA Q9JJS7 51 31 -
PTLWLFIFRLRPWDATA P2Y4_HUMAN 55 35 -

Motif 3 width=15
Element Seqn Id St Int Rpt
LRAIRWGRPRFASLL O35811 137 69 -
LRAIRWGRPRFAGLL Q9JJS7 137 69 -
LRALRWGRPRLAGLL P2Y4_HUMAN 141 69 -

Motif 4 width=14
Element Seqn Id St Int Rpt
LFFVTTNANGTTIL O35811 167 15 -
LFFVTTNANGTTIL Q9JJS7 167 15 -
LFFVTTSNKGTTVL P2Y4_HUMAN 171 15 -

Motif 5 width=21
Element Seqn Id St Int Rpt
RLYRPLPGAGQSSSRLRSLRT O35811 222 41 -
RLYRPLPGAGQSSSRLRSLRT Q9JJS7 222 41 -
RLYQPLPGSAQSSSRLRSLRT P2Y4_HUMAN 226 41 -

Motif 6 width=11
Element Seqn Id St Int Rpt
ARLLQADCHVL O35811 267 24 -
ARLLNAECRVL Q9JJS7 267 24 -
ARLLEADCRVL P2Y4_HUMAN 271 24 -

Motif 7 width=17
Element Seqn Id St Int Rpt
LFTGDKYRNQLQQLCRG O35811 303 25 -
LFTGDKYRNQLQQLCRG Q9JJS7 303 25 -
LLTGDKYRRQLRQLCGG P2Y4_HUMAN 307 25 -

Motif 8 width=16
Element Seqn Id St Int Rpt
SKPKPRTAASSLALVT O35811 320 0 -
STPKRRTTASSLALVT Q9JJS7 320 0 -
GKPQPRTAASSLALVS P2Y4_HUMAN 324 0 -

Motif 9 width=25
Element Seqn Id St Int Rpt
LHEESISRWADTHQDSTFSAYEGDR O35811 336 0 -
LHEESISRWADIHQDSIFPAYEGDR Q9JJS7 336 0 -
LPEDSSCRWAATPQDSSCSTPRADR P2Y4_HUMAN 340 0 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
ESLLFTSLGPSPSSG O35811 5 5 -
DSLLFTSLGPSPSSG Q9JJS7 5 5 -
ESSLLRSLGLSPGPG P2Y4_HUMAN 5 5 -

Motif 2 width=17
Element Seqn Id St Int Rpt
PTLWLFLFRLRPWDATA O35811 51 31 -
PTLWLFLFRLRPWDATA Q9JJS7 51 31 -
PTLWLFIFRLRPWDATA P2Y4_HUMAN 55 35 -

Motif 3 width=15
Element Seqn Id St Int Rpt
LRAIRWGRPRFASLL O35811 137 69 -
LRAIRWGRPRFAGLL Q9JJS7 137 69 -
LRALRWGRPRLAGLL P2Y4_HUMAN 141 69 -

Motif 4 width=14
Element Seqn Id St Int Rpt
LFFVTTNANGTTIL O35811 167 15 -
LFFVTTNANGTTIL Q9JJS7 167 15 -
LFFVTTSNKGTTVL P2Y4_HUMAN 171 15 -

Motif 5 width=21
Element Seqn Id St Int Rpt
RLYRPLPGAGQSSSRLRSLRT O35811 222 41 -
RLYRPLPGAGQSSSRLRSLRT Q9JJS7 222 41 -
RLYQPLPGSAQSSSRLRSLRT P2Y4_HUMAN 226 41 -

Motif 6 width=11
Element Seqn Id St Int Rpt
ARLLQADCHVL O35811 267 24 -
ARLLNAECRVL Q9JJS7 267 24 -
ARLLEADCRVL P2Y4_HUMAN 271 24 -

Motif 7 width=17
Element Seqn Id St Int Rpt
LFTGDKYRNQLQQLCRG O35811 303 25 -
LFTGDKYRNQLQQLCRG Q9JJS7 303 25 -
LLTGDKYRRQLRQLCGG P2Y4_HUMAN 307 25 -

Motif 8 width=16
Element Seqn Id St Int Rpt
SKPKPRTAASSLALVT O35811 320 0 -
STPKRRTTASSLALVT Q9JJS7 320 0 -
GKPQPRTAASSLALVS P2Y4_HUMAN 324 0 -

Motif 9 width=25
Element Seqn Id St Int Rpt
LHEESISRWADTHQDSTFSAYEGDR O35811 336 0 -
LHEESISRWADIHQDSIFPAYEGDR Q9JJS7 336 0 -
LPEDSSCRWAATPQDSSCSTPRADR P2Y4_HUMAN 340 0 -