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PR00555

Identifier
ADENOSINEA3R  [View Relations]  [View Alignment]  
Accession
PR00555
No. of Motifs
6
Creation Date
14-AUG-1996  (UPDATE 06-JUN-1999)
Title
Adenosine A3 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00424 ADENOSINER
INTERPRO; IPR000466
GCRDB; GCR_0177; GCR_0373; GCR_0746; GCR_0791; GCR_0389
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,
Adenosine and adenine nucleotides.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp19-31.

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 role in energy metabolism, purines (especially
adenosine and adenine nucleotides) produce a wide range of pharmacological
effects mediated by activation of cell surface receptors [6]. Distinct
receptors exist for adenosine. In the periphery, the main effects of 
adenosine include vasodilation, bronchoconstriction, immunosuppresion,
inhibition of platelet aggregation, cardiac depression, stimulation of
nociceptive afferents, inhibition of neurotransmitter release and
inhibition of the release of other factors, e.g. hormones [6]. In the CNS,
adenosine exerts a pre- and post-synaptic depressant action, reducing motor
activity, depressing respiration, inducing sleep and relieving anxiety. The
physiological role of adenosine is thought to be to adjust energy demands
in line with oxygen supply. Many of the clinical actions of methylxanthines
are thought to be mediated through antagonism of adenosine receptors. Four
subtypes of receptor have been identified, designated A1, A2A, A2B and A3.
 
A3 receptors are found in high levels in the testis, and in lower levels in
the lung, kidney and heart [6]. They are also found in low levels in regions
of the CNS (including the cerebral cortex, striatum and olfactory bulb). The
presence in high levels in the testis has led to the suggestion that it may
play a role in reproduction [6]. The A3 receptor inhibits adenylyl cyclase
through a pertussis-toxin-sensitive G protein, probably belonging to the
Gi/Go class.
 
ADENOSINEA3R is a 6-element fingerprint that provides a signature for the
A3 family of adenosine 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 adenosine A3 receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motif 1
lies at the N-terminus; motif 2 lies in the first external loop; motif 3
lies in the N-terminal portion of TM domain 3; motif 4 lies in the third
cytoplasmic loop; motif 5 spans the third external loop; and motif 6 lies
at the C-terminus. A single iteration on OWL28.1 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, and 1
partial match.
Summary Information
   4 codes involving  6 elements
1 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6444444
5011111
4000000
3000000
2000000
123456
True Positives
AA3R_CANFA    AA3R_HUMAN    AA3R_RAT      AA3R_SHEEP    
True Positive Partials
Codes involving 5 elements
AA3R_RABIT
Sequence Titles
AA3R_CANFA  Adenosine A3 receptor - Canis familiaris (Dog). 
AA3R_HUMAN Adenosine A3 receptor - Homo sapiens (Human).
AA3R_RAT Adenosine A3 receptor (TGPCR1) - Rattus norvegicus (Rat).
AA3R_SHEEP Adenosine A3 receptor - Ovis aries (Sheep).

AA3R_RABIT Adenosine A3 receptor - Oryctolagus cuniculus (Rabbit).
Scan History
OWL28_1    1  100  NSINGLE    
SPTR37_9f 2 6 NSINGLE
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
TSALWLQITYVTM AA3R_RAT 8 8 -
TAVSWTSVTYITV AA3R_SHEEP 6 6 -
TALSLANVTYITM AA3R_HUMAN 6 6 -
TSALWLQITYITM RSPA3I 8 8 -
TSALWLQITYITM RNGPCR 8 8 -

Motif 2 width=12
Element Seqn Id St Int Rpt
KLNPSLQTTTFY AA3R_HUMAN 38 19 -
KLNRTLRTTTFY RNGPCR 40 19 -
KLNRTLRTTTFY RSPA3I 40 19 -
KLNPSLQTTTFY AA3R_SHEEP 38 19 -
KLNRTLRTTTFY AA3R_RAT 40 19 -

Motif 3 width=16
Element Seqn Id St Int Rpt
LFMTCLMLIFTHASIM AA3R_SHEEP 84 34 -
LFMSCVLLVFTHASIM RSPA3I 86 34 -
LFMSCVLLVFTHASIM RNGPCR 86 34 -
LFMTCLLLIFTHASIM AA3R_HUMAN 84 34 -
LFMSCVLLVFTHASIM AA3R_RAT 86 34 -

Motif 4 width=17
Element Seqn Id St Int Rpt
RNKLSLNLSNSKETGAF AA3R_HUMAN 205 105 -
RNKLSQNLTGFRETRAF AA3R_RAT 207 105 -
RNKLSQNLTGFRETRAF RSPA3I 224 122 -
RNKLSQNLTGFRETRAF RNGPCR 207 105 -
RNRLSQSFSGSRETGAF AA3R_SHEEP 204 104 -

Motif 5 width=18
Element Seqn Id St Int Rpt
NFVSYFNVKIPEIAMCLG RSPA3I 269 28 -
NCIIYFNGEVPQLVLYMG AA3R_HUMAN 250 28 -
NCILYFDGQVPQTVLYLG AA3R_SHEEP 249 28 -
NFVSYFNVKIPEIAMCLG AA3R_RAT 252 28 -
NFVSYFNVKIPEIAMCLG RNGPCR 252 28 -

Motif 6 width=18
Element Seqn Id St Int Rpt
LKACVVCHPSDSLDTSIE AA3R_HUMAN 297 29 -
LRACRLCQTSDSLDSNLE AA3R_RAT 299 29 -
LKACVMCQPSKSMDPSTE AA3R_SHEEP 296 29 -
LRACRLCQTSDSLDSNLE RSPA3I 316 29 -
LRACRLCQTSDSLDSNLE RNGPCR 299 29 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
TALSLANVTYITM AA3R_HUMAN 6 6 -
TALLLANVTYITV AA3R_CANFA 6 6 -
TAVSWTSVTYITV AA3R_SHEEP 6 6 -
TSALWLQITYVTM AA3R_RAT 8 8 -

Motif 2 width=12
Element Seqn Id St Int Rpt
KLNPSLQTTTFY AA3R_HUMAN 38 19 -
KLNPSLQTTTFY AA3R_CANFA 38 19 -
KLNPSLQTTTFY AA3R_SHEEP 38 19 -
KLNRTLRTTTFY AA3R_RAT 40 19 -

Motif 3 width=16
Element Seqn Id St Int Rpt
LFMTCLLLIFTHASIM AA3R_HUMAN 84 34 -
LFMTCLLLIFTHASIM AA3R_CANFA 84 34 -
LFMTCLMLIFTHASIM AA3R_SHEEP 84 34 -
LFMSCVLLVFTHASIM AA3R_RAT 86 34 -

Motif 4 width=17
Element Seqn Id St Int Rpt
RNKLSLNLSNSKETGAF AA3R_HUMAN 205 105 -
RNKLNQNFSSSKETGAF AA3R_CANFA 205 105 -
RNRLSQSFSGSRETGAF AA3R_SHEEP 204 104 -
RNKLSQNLTGFRETRAF AA3R_RAT 207 105 -

Motif 5 width=18
Element Seqn Id St Int Rpt
NCIIYFNGEVPQLVLYMG AA3R_HUMAN 250 28 -
NCITYFHGEVPQIILYLG AA3R_CANFA 250 28 -
NCILYFDGQVPQTVLYLG AA3R_SHEEP 249 28 -
NFVSYFNVKIPEIAMCLG AA3R_RAT 252 28 -

Motif 6 width=18
Element Seqn Id St Int Rpt
LKACVVCHPSDSLDTSIE AA3R_HUMAN 297 29 -
FKTYMICQSSDSLDSSTE AA3R_CANFA 297 29 -
LKACVMCQPSKSMDPSTE AA3R_SHEEP 296 29 -
LRACRLCQTSDSLDSNLE AA3R_RAT 299 29 -