WORKLIST ENTRIES (1):
P2Y6PRNOCPTR View alignment View Structure P2Y6 purinoceptor signature
Type of fingerprint: COMPOUND with 6 elements
Links:
PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
PRINTS; PR00251 BACTRLOPSIN
PRINTS; PR01157 P2YPURNOCPTR; PR00595 P2Y1PRNOCPTR; PR00594 P2Y2PRNOCPTR
PRINTS; PR01065 P2Y3PRNOCPTR; PR01066 P2Y4PRNOCPTR; PR01569 P2Y12PRNCPTR
PRINTS; PR01735 P2Y13PRNCPTR
INTERPRO; IPR001973
Creation date 31-JAN-1999; UPDATE 29-NOV-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. 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).
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].
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 FINGERPRINT INDEX
6| 2 2 2 2 2 2
5| 0 0 0 0 0 0
4| 0 0 0 0 0 0
3| 0 0 0 0 0 0
2| 0 0 0 0 0 0
--+-------------------------------
| 1 2 3 4 5 6
True positives..
P2Y6_HUMAN P2Y6_RAT
PROTEIN 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 MOTIF SETS
P2Y6PRNOCPTR1 Length of motif = 17 Motif number = 1
P2Y6 purinoceptor motif I - 1
PCODE ST INT
ERDNGTIQAPGLPPTTC P2Y6_RAT 2 2
EWDNGTGQALGLPPTTC P2Y6_HUMAN 2 2
P2Y6PRNOCPTR2 Length of motif = 11 Motif number = 2
P2Y6 purinoceptor motif II - 1
PCODE ST INT
CVIAQICASRR P2Y6_RAT 46 27
CVITQICTSRR P2Y6_HUMAN 46 27
P2Y6PRNOCPTR3 Length of motif = 13 Motif number = 3
P2Y6 purinoceptor motif III - 1
PCODE ST INT
PILSTRYLPYGMA P2Y6_RAT 183 126
PALATHYMPYGMA P2Y6_HUMAN 183 126
P2Y6PRNOCPTR4 Length of motif = 20 Motif number = 4
P2Y6 purinoceptor motif IV - 1
PCODE ST INT
CRMARRLCRQDGPAGPVAQE P2Y6_RAT 213 17
CLLACRLCRQDGPAEPVAQE P2Y6_HUMAN 213 17
P2Y6PRNOCPTR5 Length of motif = 14 Motif number = 5
P2Y6 purinoceptor motif V - 1
PCODE ST INT
PGVSCPVLETFAAA P2Y6_RAT 269 36
PGVPCTVLEAFAAA P2Y6_HUMAN 269 36
P2Y6PRNOCPTR6 Length of motif = 18 Motif number = 6
P2Y6 purinoceptor motif VI - 1
PCODE ST INT
RRQPHDLLQKLTAKWQRQ P2Y6_RAT 309 26
RRRPHELLQKLTAKWQRQ P2Y6_HUMAN 309 26
FINAL MOTIF SETS
P2Y6PRNOCPTR1 Length of motif = 17 Motif number = 1
P2Y6 purinoceptor motif I - 2
PCODE ST INT
EWDNGTGQALGLPPTTC P2Y6_HUMAN 2 2
ERDNGTIQAPGLPPTTC P2Y6_RAT 2 2
P2Y6PRNOCPTR2 Length of motif = 11 Motif number = 2
P2Y6 purinoceptor motif II - 2
PCODE ST INT
CVITQICTSRR P2Y6_HUMAN 46 27
CVIAQICASRR P2Y6_RAT 46 27
P2Y6PRNOCPTR3 Length of motif = 13 Motif number = 3
P2Y6 purinoceptor motif III - 2
PCODE ST INT
PALATHYMPYGMA P2Y6_HUMAN 183 126
PILSTRYLPYGMA P2Y6_RAT 183 126
P2Y6PRNOCPTR4 Length of motif = 20 Motif number = 4
P2Y6 purinoceptor motif IV - 2
PCODE ST INT
CLLACRLCRQDGPAEPVAQE P2Y6_HUMAN 213 17
CRMARRLCRQDGPAGPVAQE P2Y6_RAT 213 17
P2Y6PRNOCPTR5 Length of motif = 14 Motif number = 5
P2Y6 purinoceptor motif V - 2
PCODE ST INT
PGVPCTVLEAFAAA P2Y6_HUMAN 269 36
PGVSCPVLETFAAA P2Y6_RAT 269 36
P2Y6PRNOCPTR6 Length of motif = 18 Motif number = 6
P2Y6 purinoceptor motif VI - 2
PCODE ST INT
RRRPHELLQKLTAKWQRQ P2Y6_HUMAN 309 26
RRQPHDLLQKLTAKWQRQ P2Y6_RAT 309 26
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