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PR01068

Identifier
P2Y6PRNOCPTR  [View Relations]  [View Alignment]  
Accession
PR01068
No. of Motifs
6
Creation Date
31-JAN-1999  (UPDATE 29-NOV-2001)
Title
P2Y6 purinoceptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01157 P2YPURNOCPTR
INTERPRO; IPR001973
GCRDB; GCR_1520
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. CHANG, K., HANAOKA, K., KUMADA, M. AND TAKUWA, Y.
Molecular cloning and functional analysis of a novel P2 nucleotide receptor.
J.BIOL.CHEM. 270 26152-26158 (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]. 
 
cDNA encoding the P2Y6 receptor has been isolated and functionally
characterised [8]. The receptor shows 44 and 38% amino acid identity with
rat P2U and chicken P2Y receptors, respectively [8]. P2Y6 is functionally
coupled to phospholipase C, but not to adenylate cyclase in C6 rat glioma
cells transfected with the cloned P2 expression vector [8]. P2Y6 mRNA is
abundantly expressed in various rat tissues, including lung, stomach, 
intestine, spleen, mesentery, heart, and, most prominently, aorta [8]. The
receptor displays pharmacological characteristics distinct from any P2Y 
receptor subtype thus far identified, having a preference for uridine 
nucleotides, with UDP being 100-fold more potent than UTP [8]. 
 
P2Y6PRNOCPTR is a 6-element fingerprint that provides a signature for the
P2Y6 purinoceptor. The fingerprint was derived from an initial alignment of 
2 sequences: the motifs were drawn from conserved regions spanning the full
alignment length, focusing on those sections that characterise the P2Y6 
receptors but distinguish them from the rest of the P2Y receptor family -
motif 1 resides at the N-terminus; motif 2 spans the C-terminus of TM 
domain 1, leading into the first cytoplasmic loop; motif 3 lies in the 
second external loop; motif 4 spans the C-terminus of TM domain 5, leading 
into the third cytoplasmic loop; motif 5 lies in the third external loop; 
and motif 6 resides at the C-terminus. A single iteration on OWL31.1 was 
required to reach convergence, no further sequences being identified beyond 
the starting set.
 
An update on SPTR37_9f identified no further matches.
Summary Information
2 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
6222222
5000000
4000000
3000000
2000000
123456
True Positives
P2Y6_HUMAN    P2Y6_RAT      
Sequence Titles
P2Y6_HUMAN  P2Y PURINOCEPTOR 6 (P2Y6) - HOMO SAPIENS (HUMAN). 
P2Y6_RAT P2Y PURINOCEPTOR 6 (P2Y6) - RATTUS NORVEGICUS (RAT).
Scan History
OWL31_1    1  100  NSINGLE    
SPTR37_9f 2 3 NSINGLE
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
EWDNGTGQALGLPPTTC P2Y6_HUMAN 2 2 -
ERDNGTIQAPGLPPTTC P2Y6_RAT 2 2 -

Motif 2 width=11
Element Seqn Id St Int Rpt
CVITQICTSRR P2Y6_HUMAN 46 27 -
CVIAQICASRR P2Y6_RAT 46 27 -

Motif 3 width=13
Element Seqn Id St Int Rpt
PALATHYMPYGMA P2Y6_HUMAN 183 126 -
PILSTRYLPYGMA P2Y6_RAT 183 126 -

Motif 4 width=20
Element Seqn Id St Int Rpt
CLLACRLCRQDGPAEPVAQE P2Y6_HUMAN 213 17 -
CRMARRLCRQDGPAGPVAQE P2Y6_RAT 213 17 -

Motif 5 width=14
Element Seqn Id St Int Rpt
PGVPCTVLEAFAAA P2Y6_HUMAN 269 36 -
PGVSCPVLETFAAA P2Y6_RAT 269 36 -

Motif 6 width=18
Element Seqn Id St Int Rpt
RRRPHELLQKLTAKWQRQ P2Y6_HUMAN 309 26 -
RRQPHDLLQKLTAKWQRQ P2Y6_RAT 309 26 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
EWDNGTGQALGLPPTTC P2Y6_HUMAN 2 2 -
ERDNGTIQAPGLPPTTC P2Y6_RAT 2 2 -

Motif 2 width=11
Element Seqn Id St Int Rpt
CVITQICTSRR P2Y6_HUMAN 46 27 -
CVIAQICASRR P2Y6_RAT 46 27 -

Motif 3 width=13
Element Seqn Id St Int Rpt
PALATHYMPYGMA P2Y6_HUMAN 183 126 -
PILSTRYLPYGMA P2Y6_RAT 183 126 -

Motif 4 width=20
Element Seqn Id St Int Rpt
CLLACRLCRQDGPAEPVAQE P2Y6_HUMAN 213 17 -
CRMARRLCRQDGPAGPVAQE P2Y6_RAT 213 17 -

Motif 5 width=14
Element Seqn Id St Int Rpt
PGVPCTVLEAFAAA P2Y6_HUMAN 269 36 -
PGVSCPVLETFAAA P2Y6_RAT 269 36 -

Motif 6 width=18
Element Seqn Id St Int Rpt
RRRPHELLQKLTAKWQRQ P2Y6_HUMAN 309 26 -
RRQPHDLLQKLTAKWQRQ P2Y6_RAT 309 26 -