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PR00553

Identifier
ADENOSINA2AR  [View Relations]  [View Alignment]  
Accession
PR00553
No. of Motifs
8
Creation Date
14-AUG-1996  (UPDATE 06-JUN-1999)
Title
Adenosine A2A receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00424 ADENOSINER
INTERPRO; IPR001513
GCRDB; GCR_0418; GCR_0486; GCR_0019; GCR_0424; GCR_0506; GCR_0659
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.
 
A2A receptors have a limited distribution in the brain and are found in the
striatum, olfactory tubercle and nucleus accumbens. In the periphery, A2
receptors mediate vasodilation, immunosuppression, inhibition of platelet
aggregation and gluconeogenesis [6]. The receptors activate adenylyl
cyclase through Gs.
 
ADENOSINA2AR is an 8-element fingerprint that provides a signature for the
A2A family of adenosine receptors. The fingerprint was derived from an
initial alignment of 6 sequences: the motifs were drawn from conserved
sections within either loop or C-terminal regions, focusing on those areas 
of the alignment that characterise the adenosine A2A receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motif 1
spans the C-terminus of TM domain 1, leading into the first cytoplasmic
loop; motif 2 lies in the first external loop; motif 3 lies in the second
external loop; motif 4 lies in the third cytoplasmic loop; motif 5 lies in
the third external loop; and motifs 6-8 span the C-terminus. A single
iteration on OWL28.1 was required to reach convergence, no further sequences
being identified beyond the starting set. A single partial match was also
found, I48932, a mouse adenosine receptor fragment that matches motifs 2
and 3.
 
An update on SPTR37_9f identified a true set of 5 sequences.
Summary Information
5 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 Feature Index
855555555
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
AA2A_CANFA    AA2A_CAVPO    AA2A_HUMAN    AA2A_MOUSE    
AA2A_RAT
Sequence Titles
AA2A_CANFA  ADENOSINE A2A RECEPTOR - CANIS FAMILIARIS (DOG). 
AA2A_CAVPO ADENOSINE A2A RECEPTOR - CAVIA PORCELLUS (GUINEA PIG).
AA2A_HUMAN ADENOSINE A2A RECEPTOR - HOMO SAPIENS (HUMAN).
AA2A_MOUSE ADENOSINE A2A RECEPTOR - MUS MUSCULUS (MOUSE).
AA2A_RAT ADENOSINE A2A RECEPTOR - RATTUS NORVEGICUS (RAT).
Scan History
OWL28_1    1  50   NSINGLE    
SPTR37_9f 2 7 NSINGLE
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
CWAVWLNSNLQNV AA2A_HUMAN 28 28 -
CWAVWINSNLQNV AA2A_CAVPO 25 25 -
CWAVWINSNLQNV A48974 25 25 -
CWAVWINSNLQNV I48095 25 25 -
CWAVWINSNLQNV AA2A_RAT 25 25 -
CWAVWLNSNLQNV AA2A_CANFA 28 28 -

Motif 2 width=9
Element Seqn Id St Int Rpt
TGFCAACHN AA2A_CANFA 68 27 -
TGFCAACHG AA2A_RAT 65 27 -
TGFCAACHG AA2A_CAVPO 65 27 -
TGFCAACHG AA2A_HUMAN 68 27 -
TGFCAACHG A48974 65 27 -
TGFCAACHG I48095 65 27 -

Motif 3 width=10
Element Seqn Id St Int Rpt
CGEGRVTCLF A48974 154 80 -
CDEGQVTCLF I48095 156 82 -
CDEGQVTCLF AA2A_CAVPO 156 82 -
CGEGQVACLF AA2A_HUMAN 159 82 -
CGEGQVACLF AA2A_CANFA 159 82 -
CGEGRVTCLF AA2A_RAT 154 80 -

Motif 4 width=15
Element Seqn Id St Int Rpt
KQMESQPLPGERTRS A48974 204 40 -
KQMESQPLPGERTRS I48095 206 40 -
KQMESQPLPGERTRS AA2A_RAT 204 40 -
KQMESQPLPGERARS AA2A_CANFA 209 40 -
KQMESQPLPGERARS AA2A_HUMAN 209 40 -
KQMESQPLPGERTRS AA2A_CAVPO 206 40 -

Motif 5 width=13
Element Seqn Id St Int Rpt
CFTFFCPECSHAP AA2A_CANFA 254 30 -
CFTFFCSTCRHAP AA2A_RAT 249 30 -
CFTFFCPECGHAP I48095 251 30 -
CFTFFCSTCRHAP A48974 249 30 -
CFTFFCPECDHAP AA2A_CAVPO 251 30 -
CFTFFCPDCSHAP AA2A_HUMAN 254 30 -

Motif 6 width=18
Element Seqn Id St Int Rpt
RSHILRRRELFKAGGTSA I48095 301 37 -
RTHVLRRQEPFQAGGSSA A48974 299 37 -
RTHVLRRQEPFQAGGSSA AA2A_RAT 299 37 -
RSHVLRRREPFKAGGTSA AA2A_CANFA 304 37 -
RSHVLRQQEPFKAAGTSA AA2A_HUMAN 304 37 -
RSHILRRRELFKAGGTSA AA2A_CAVPO 301 37 -

Motif 7 width=20
Element Seqn Id St Int Rpt
HGSDGEQVSLRLNGHPPGVW AA2A_HUMAN 327 5 -
HSPEGEQVSLRLNGHPPGVW AA2A_CAVPO 324 5 -
HSPEGEQVSLRLNGHPPGVW I48095 324 5 -
HSTEGEQVSLRLNGHPLGVW A48974 322 5 -
HSTEGEQVSLRLNGHPLGVW AA2A_RAT 322 5 -
HGSDGEQISLRLNGHPPGVW AA2A_CANFA 327 5 -

Motif 8 width=19
Element Seqn Id St Int Rpt
ANGSATHSGRRPNGYTLGL AA2A_RAT 342 0 -
ANGSATHSGRRPNGYTLGL A48974 342 0 -
ANGSALRPEQRPNGYVLGL AA2A_CAVPO 344 0 -
ANGSAPHPERRPNGYALGL AA2A_HUMAN 347 0 -
ANGSAPHPERRPNGYTLGL AA2A_CANFA 347 0 -
ANGSAPRPEQRPNGYVLGL I48095 344 0 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
CWAVWINSNLQNV AA2A_RAT 25 25 -
CWAVWINSNLQNV AA2A_MOUSE 25 25 -
CWAVWLNSNLQNV AA2A_CANFA 28 28 -
CWAVWLNSNLQNV AA2A_HUMAN 28 28 -
CWAVWINSNLQNV AA2A_CAVPO 25 25 -

Motif 2 width=9
Element Seqn Id St Int Rpt
TGFCAACHG AA2A_RAT 65 27 -
TGFCAACHG AA2A_MOUSE 65 27 -
TGFCAACHN AA2A_CANFA 68 27 -
TGFCAACHG AA2A_HUMAN 68 27 -
TGFCAACHG AA2A_CAVPO 65 27 -

Motif 3 width=10
Element Seqn Id St Int Rpt
CGEGRVTCLF AA2A_RAT 154 80 -
CGEGRVTCLF AA2A_MOUSE 154 80 -
CGEGQVACLF AA2A_CANFA 159 82 -
CGEGQVACLF AA2A_HUMAN 159 82 -
CDEGQVTCLF AA2A_CAVPO 156 82 -

Motif 4 width=15
Element Seqn Id St Int Rpt
KQMESQPLPGERTRS AA2A_RAT 204 40 -
KQMESQPLPGERTRS AA2A_MOUSE 204 40 -
KQMESQPLPGERARS AA2A_CANFA 209 40 -
KQMESQPLPGERARS AA2A_HUMAN 209 40 -
KQMESQPLPGERTRS AA2A_CAVPO 206 40 -

Motif 5 width=13
Element Seqn Id St Int Rpt
CFTFFCSTCRHAP AA2A_RAT 249 30 -
CFTFFCSTCQHAP AA2A_MOUSE 249 30 -
CFTFFCPECSHAP AA2A_CANFA 254 30 -
CFTFFCPDCSHAP AA2A_HUMAN 254 30 -
CFTFFCPECDHAP AA2A_CAVPO 251 30 -

Motif 6 width=18
Element Seqn Id St Int Rpt
RTHVLRRQEPFQAGGSSA AA2A_RAT 299 37 -
RTHVLRRQEPFRAGGSSA AA2A_MOUSE 299 37 -
RSHVLRRREPFKAGGTSA AA2A_CANFA 304 37 -
RSHVLRQQEPFKAAGTSA AA2A_HUMAN 304 37 -
RSHILRRRELFKAGGTSA AA2A_CAVPO 301 37 -

Motif 7 width=20
Element Seqn Id St Int Rpt
HSTEGEQVSLRLNGHPLGVW AA2A_RAT 322 5 -
HSTEGEQVSLRLNGHPLGVW AA2A_MOUSE 322 5 -
HGSDGEQISLRLNGHPPGVW AA2A_CANFA 327 5 -
HGSDGEQVSLRLNGHPPGVW AA2A_HUMAN 327 5 -
HSPEGEQVSLRLNGHPPGVW AA2A_CAVPO 324 5 -

Motif 8 width=19
Element Seqn Id St Int Rpt
ANGSATHSGRRPNGYTLGL AA2A_RAT 342 0 -
ANGSAPHSGRRPNGYTLGP AA2A_MOUSE 342 0 -
ANGSAPHPERRPNGYTLGL AA2A_CANFA 347 0 -
ANGSAPHPERRPNGYALGL AA2A_HUMAN 347 0 -
ANGSALRPEQRPNGYVLGL AA2A_CAVPO 344 0 -