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PR00552

Identifier
ADENOSINEA1R  [View Relations]  [View Alignment]  
Accession
PR00552
No. of Motifs
5
Creation Date
14-AUG-1996  (UPDATE 06-JUN-1999)
Title
Adenosine A1 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00424 ADENOSINER
INTERPRO; IPR001068
GCRDB; GCR_0504; GCR_0682; GCR_0729; GCR_0111; GCR_0112; GCR_0284

GCRDB; GCR_0292
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.
 
A1 receptors are distributed widely in peripheral tissues (e.g., heart, 
adipose tissue, kidney, stomach and pancreas), where they have a mainly 
inhibitory role, and are also found in peripheral nerves (e.g., in the
intestine and vas deferens) [6]. In the CNS, they are present in high
levels, notably in the cerebral cortex, hippocampus, cerebellum, thalamus
and striatum. The receptors inhibit adenylyl cyclase and voltage-dependent
calcium channels, and activate potassium channels through a pertussis-toxin-
sensitive G protein, probably of the Gi/Go class.
 
ADENOSINEA1R is a 5-element fingerprint that provides a signature for the
A1 family of adenosine receptors. The fingerprint was derived from an
initial alignment of 7 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 A1 receptors
but distinguish them from the rest of the rhodopsin-like superfamily - motif
1 lies at the N-terminus; motif 2 spans the first cytoplasmic loop; motif 3 
spans the first external loop; motif 4 lies in the third cytoplasmic loop;
and motif 5 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. Two partial matches were also found, both of which are
adenosine receptor fragments.
 
An update on SPTR37_9f identified a true set of 8 sequences.
Summary Information
8 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
588888
400000
300000
200000
12345
True Positives
AA1R_BOVIN    AA1R_CANFA    AA1R_CAVPO    AA1R_CHICK    
AA1R_HUMAN AA1R_RABIT AA1R_RAT O08766
Sequence Titles
AA1R_BOVIN  Adenosine receptor A1 - Bos taurus (Bovine).  
AA1R_CANFA Adenosine receptor A1 - Canis familiaris (Dog).
AA1R_CAVPO Adenosine receptor A1 - Cavia porcellus (Guinea pig).
AA1R_CHICK Adenosine receptor A1 - Gallus gallus (Chicken).
AA1R_HUMAN Adenosine receptor A1 - Homo sapiens (Human).
AA1R_RABIT Adenosine receptor A1 - Oryctolagus cuniculus (Rabbit).
AA1R_RAT Adenosine receptor A1 - Rattus norvegicus (Rat).
O08766 A1 RECEPTOR 326 AS - RATTUS NORVEGICUS (RAT).
Scan History
OWL28_1    1  50   NSINGLE    
SPTR37_9f 2 9 NSINGLE
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
ISAFQAAYIGI AA1R_BOVIN 5 5 -
ISAFQAAYIGI AA1R_CANFA 5 5 -
VSAFQAAYIGI AA1R_CAVPO 5 5 -
ISAFQAAYIGI AA1R_RABIT 5 5 -
VTAFQAAYISI S55231 5 5 -
ISAFQAAYIGI AA1R_HUMAN 5 5 -
ISAFQAAYIGI AA1R_RAT 5 5 -

Motif 2 width=13
Element Seqn Id St Int Rpt
VKVNQALRDATFC AA1R_BOVIN 34 18 -
VKVNQALRDATFC AA1R_CAVPO 34 18 -
VKMNQALRDATFC S55231 34 18 -
VKVNQALRDATFC AA1R_RABIT 34 18 -
VKVNQALRDATFC AA1R_HUMAN 34 18 -
VKVNQALRDATFC AA1R_RAT 34 18 -
VKVNQALRDATFC AA1R_CANFA 34 18 -

Motif 3 width=13
Element Seqn Id St Int Rpt
LINIGPQTYFHTC AA1R_HUMAN 68 21 -
IINIGPQTEFYSC S55231 68 21 -
LINIGPQTYFHTC AA1R_RAT 68 21 -
LINIGPRTYFHTC AA1R_BOVIN 68 21 -
LINIGPRTYFHTC AA1R_CANFA 68 21 -
LINIGPQTYFHTC AA1R_CAVPO 68 21 -
LINIGPETYFHTC AA1R_RABIT 68 21 -

Motif 4 width=16
Element Seqn Id St Int Rpt
LSKKASASSGDPHKYY AA1R_RABIT 211 130 -
LNKKVSASSGDPQKYY AA1R_HUMAN 211 130 -
LNKKVSASSGDPQKYY AA1R_RAT 211 130 -
LNKKVSSSSNDPQKYY S55231 211 130 -
LSKKVSASSGDPQKYY AA1R_BOVIN 211 130 -
LGKKVSASSGDPQKYY AA1R_CANFA 211 130 -
LSKKVSASSGDPQKYY AA1R_CAVPO 211 130 -

Motif 5 width=14
Element Seqn Id St Int Rpt
VTFLKIWNDHFRCQ AA1R_CANFA 297 70 -
VTFLKIWNDHFRCR AA1R_RABIT 297 70 -
VTFLKIWNDHFRCQ AA1R_HUMAN 297 70 -
TAFLQIWNQYFCCK S55231 297 70 -
VTFLKIWNDHFRCQ AA1R_RAT 297 70 -
VTFLKIWNDHFRCQ AA1R_BOVIN 297 70 -
VTFLKIWNDHFRCQ AA1R_CAVPO 297 70 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
ISAFQAAYIGI AA1R_HUMAN 5 5 -
ISAFQAAYIGI O08766 5 5 -
ISAFQAAYIGI AA1R_RAT 5 5 -
ISAFQAAYIGI AA1R_BOVIN 5 5 -
ISAFQAAYIGI AA1R_CANFA 5 5 -
VSAFQAAYIGI AA1R_CAVPO 5 5 -
ISAFQAAYIGI AA1R_RABIT 5 5 -
VTAFQAAYISI AA1R_CHICK 5 5 -

Motif 2 width=13
Element Seqn Id St Int Rpt
VKVNQALRDATFC AA1R_HUMAN 34 18 -
VKVNQALRDATFC O08766 34 18 -
VKVNQALRDATFC AA1R_RAT 34 18 -
VKVNQALRDATFC AA1R_BOVIN 34 18 -
VKVNQALRDATFC AA1R_CANFA 34 18 -
VKVNQALRDATFC AA1R_CAVPO 34 18 -
VKVNQALRDATFC AA1R_RABIT 34 18 -
VKMNQALRDATFC AA1R_CHICK 34 18 -

Motif 3 width=13
Element Seqn Id St Int Rpt
LINIGPQTYFHTC AA1R_HUMAN 68 21 -
LINIGPQTYFHTC O08766 68 21 -
LINIGPQTYFHTC AA1R_RAT 68 21 -
LINIGPRTYFHTC AA1R_BOVIN 68 21 -
LINIGPRTYFHTC AA1R_CANFA 68 21 -
LINIGPQTYFHTC AA1R_CAVPO 68 21 -
LINIGPETYFHTC AA1R_RABIT 68 21 -
IINIGPQTEFYSC AA1R_CHICK 68 21 -

Motif 4 width=16
Element Seqn Id St Int Rpt
LNKKVSASSGDPQKYY AA1R_HUMAN 211 130 -
LNKKVSASSGDPQKYY O08766 211 130 -
LNKKVSASSGDPQKYY AA1R_RAT 211 130 -
LSKKVSASSGDPQKYY AA1R_BOVIN 211 130 -
LGKKVSASSGDPQKYY AA1R_CANFA 211 130 -
LSKKVSASSGDPQKYY AA1R_CAVPO 211 130 -
LSKKASASSGDPHKYY AA1R_RABIT 211 130 -
LNKKVSSSSNDPQKYY AA1R_CHICK 211 130 -

Motif 5 width=14
Element Seqn Id St Int Rpt
VTFLKIWNDHFRCQ AA1R_HUMAN 297 70 -
VTFLKIWNDHFRCQ O08766 297 70 -
VTFLKIWNDHFRCQ AA1R_RAT 297 70 -
VTFLKIWNDHFRCQ AA1R_BOVIN 297 70 -
VTFLKIWNDHFRCQ AA1R_CANFA 297 70 -
VTFLKIWNDHFRCQ AA1R_CAVPO 297 70 -
VTFLKIWNDHFRCR AA1R_RABIT 297 70 -
TAFLQIWNQYFCCK AA1R_CHICK 297 70 -