WORKLIST ENTRIES (1):
P2Y2PRNOCPTR View alignment View Structure P2Y2 purinoceptor signature
Type of fingerprint: COMPOUND with 8 elements
Links:
PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
PRINTS; PR00251 BACTRLOPSIN
PRINTS; PR01157 P2YPURNOCPTR; PR00595 P2Y1PRNOCPTR; PR01065 P2Y3PRNOCPTR
PRINTS; PR01066 P2Y4PRNOCPTR; PR01068 P2Y6PRNOCPTR; PR01569 P2Y12PRNCPTR
PRINTS; PR01735 P2Y13PRNCPTR
INTERPRO; IPR000356
Creation date 10-AUG-1996; UPDATE 06-DEC-2001
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. VON KUGELGEN, I. AND WETTER, A.
Molecular pharmacology of P2Y-receptors.
NAUNYN SCHMIEDEBERGS ARCH.PHARMACOL. 362 310-323 (2000).
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 [1,2]. 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].
The P2Y2 receptor is expressed widely, with highest levels in the lung,
heart, skeletal muscle, spleen, kidney, liver and epithelia. Its main role
is in regulating ion transport in airway epithelia. P2Y2 is selectively
activated by the triphosphate nucleotides UTP and ATP, and couples to Gi
and Gq proteins to activate phospholipase C [8].
P2Y2PRNOCPTR is an 8-element fingerprint that provides a signature for the
P2Y2 purinoceptors. The fingerprint was derived from an initial alignment of
3 sequences: the motifs were drawn from conserved sections spanning
virtually the full alignment length, focusing on those areas of the
alignment that characterise the P2Y2 receptors but distinguish them from the
rest of the P2Y receptor family - motif 1 spans the N-terminus; motif 2
encodes the first cytoplasmic loop; motif 3 lies in the second cytoplasmic
loop, leading into TM domain 4; motif 4 resides at the C-terminus of TM
domain 4, leading into the second external loop; motif 5 encodes the third
external loop; and motifs 6-8 span the C-terminus. Two iterations on
SPTR40_18f were required to reach convergence, at which point a true set
comprising 4 sequences was identified.
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 FINGERPRINT INDEX
8| 4 4 4 4 4 4 4 4
7| 0 0 0 0 0 0 0 0
6| 0 0 0 0 0 0 0 0
5| 0 0 0 0 0 0 0 0
4| 0 0 0 0 0 0 0 0
3| 0 0 0 0 0 0 0 0
2| 0 0 0 0 0 0 0 0
--+-----------------------------------------
| 1 2 3 4 5 6 7 8
True positives..
P2UR_MOUSE Q9CPZ4 P2UR_RAT P2UR_HUMAN
PROTEIN TITLES
P2UR_MOUSE P2U purinoceptor 1 (ATP receptor) (P2U1) (Purinergic recepto
Q9CPZ4 PURINERGIC RECEPTOR P2Y, G-PROTEIN COUPLED 2 - Mus musculus
P2UR_RAT P2U purinoceptor 1 (ATP receptor) (P2U1) (Purinergic recepto
P2UR_HUMAN P2U purinoceptor 1 (ATP receptor) (P2U1) (Purinergic recepto
SCAN HISTORY
OWL28_1 1 100 NSINGLE
SPTR37_9f 2 140 NSINGLE
SPTR40_18f 2 100 NSINGLE
INITIAL MOTIF SETS
P2Y2PRNOCPTR1 Length of motif = 19 Motif number = 1
P2Y2 purinoceptor motif I - 1
PCODE ST INT
WNDTINGTWDGDELGYRCR P2UR_HUMAN 8 8
WNSTINGTWEGDELGYKCR P2UR_MOUSE 8 8
WNSTINGTWEGDELGYKCR P2UR_RAT 8 8
P2Y2PRNOCPTR2 Length of motif = 12 Motif number = 2
P2Y2 purinoceptor motif II - 1
PCODE ST INT
LCRLKTWNASTT P2UR_HUMAN 59 32
LCRLKTWNASTT P2UR_MOUSE 59 32
LCRLKTWNASTT P2UR_RAT 59 32
P2Y2PRNOCPTR3 Length of motif = 10 Motif number = 3
P2Y2 purinoceptor motif III - 1
PCODE ST INT
RWGRARYARR P2UR_HUMAN 143 72
RWGRARYARR P2UR_MOUSE 143 72
SWGHARYARR P2UR_RAT 143 72
P2Y2PRNOCPTR4 Length of motif = 17 Motif number = 4
P2Y2 purinoceptor motif IV - 1
PCODE ST INT
CQAPVLYFVTTSARGGR P2UR_HUMAN 164 11
CQAPVLYFVTTSVRGTR P2UR_MOUSE 164 11
CQAPVLYFVTTSVRGTR P2UR_RAT 164 11
P2Y2PRNOCPTR5 Length of motif = 11 Motif number = 5
P2Y2 purinoceptor motif V - 1
PCODE ST INT
SFRSLDLSCHT P2UR_HUMAN 270 89
SFRSLDLSCHT P2UR_MOUSE 270 89
SFRSLDLSCHT P2UR_RAT 269 88
P2Y2PRNOCPTR6 Length of motif = 14 Motif number = 6
P2Y2 purinoceptor motif VI - 1
PCODE ST INT
QRLVRFARDAKPPT P2UR_HUMAN 311 30
QRLVRFARDAKPPT P2UR_MOUSE 311 30
QRLVRFARDAKPAT P2UR_RAT 310 30
P2Y2PRNOCPTR7 Length of motif = 14 Motif number = 7
P2Y2 purinoceptor motif VII - 1
PCODE ST INT
PARRRLGLRRSDRT P2UR_HUMAN 331 6
QARRKLGLHRPNRT P2UR_MOUSE 331 6
QARRKLGLHRPNRT P2UR_RAT 330 6
P2Y2PRNOCPTR8 Length of motif = 13 Motif number = 8
P2Y2 purinoceptor motif VIII - 1
PCODE ST INT
SEDFRRTESTPAG P2UR_HUMAN 356 11
SDDSRRTESTPAG P2UR_MOUSE 353 8
SDDSRRTESTPAG P2UR_RAT 354 10
FINAL MOTIF SETS
P2Y2PRNOCPTR1 Length of motif = 19 Motif number = 1
P2Y2 purinoceptor motif I - 2
PCODE ST INT
WNSTINGTWEGDELGYKCR P2UR_MOUSE 8 8
WNSTINGTWEGDELGYKCR Q9CPZ4 8 8
WNSTINGTWEGDELGYKCR P2UR_RAT 8 8
WNDTINGTWDGDELGYRCR P2UR_HUMAN 8 8
P2Y2PRNOCPTR2 Length of motif = 12 Motif number = 2
P2Y2 purinoceptor motif II - 2
PCODE ST INT
LCRLKTWNASTT P2UR_MOUSE 59 32
LCRLKTWNASTT Q9CPZ4 59 32
LCRLKTWNASTT P2UR_RAT 59 32
LCRLKTWNASTT P2UR_HUMAN 59 32
P2Y2PRNOCPTR3 Length of motif = 10 Motif number = 3
P2Y2 purinoceptor motif III - 2
PCODE ST INT
RWGRARYARR P2UR_MOUSE 143 72
RWGRARYARR Q9CPZ4 143 72
SWGHARYARR P2UR_RAT 143 72
RWGRARYARR P2UR_HUMAN 143 72
P2Y2PRNOCPTR4 Length of motif = 17 Motif number = 4
P2Y2 purinoceptor motif IV - 2
PCODE ST INT
CQAPVLYFVTTSVRGTR P2UR_MOUSE 164 11
CQAPVLYFVTTSVRGTR Q9CPZ4 164 11
CQAPVLYFVTTSVRGTR P2UR_RAT 164 11
CQAPVLYFVTTSARGGR P2UR_HUMAN 164 11
P2Y2PRNOCPTR5 Length of motif = 11 Motif number = 5
P2Y2 purinoceptor motif V - 2
PCODE ST INT
SFRSLDLSCHT P2UR_MOUSE 270 89
SFRSLDLSCHT Q9CPZ4 270 89
SFRSLDLSCHT P2UR_RAT 269 88
SFRSLDLSCHT P2UR_HUMAN 270 89
P2Y2PRNOCPTR6 Length of motif = 14 Motif number = 6
P2Y2 purinoceptor motif VI - 2
PCODE ST INT
QRLVRFARDAKPPT P2UR_MOUSE 311 30
QRLVRFARDAKPPT Q9CPZ4 311 30
QRLVRFARDAKPAT P2UR_RAT 310 30
QRLVRFARDAKPPT P2UR_HUMAN 311 30
P2Y2PRNOCPTR7 Length of motif = 14 Motif number = 7
P2Y2 purinoceptor motif VII - 2
PCODE ST INT
QARRKLGLHRPNRT P2UR_MOUSE 331 6
QARRKLGLHRPNRT Q9CPZ4 331 6
QARRKLGLHRPNRT P2UR_RAT 330 6
PARRRLGLRRSDRT P2UR_HUMAN 331 6
P2Y2PRNOCPTR8 Length of motif = 13 Motif number = 8
P2Y2 purinoceptor motif VIII - 2
PCODE ST INT
SDDSRRTESTPAG P2UR_MOUSE 353 8
SDDSRRTESTPAG Q9CPZ4 353 8
SDDSRRTESTPAG P2UR_RAT 354 10
SEDFRRTESTPAG P2UR_HUMAN 356 11
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