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PR00424

Identifier
ADENOSINER  [View Relations]  [View Alignment]  
Accession
PR00424
No. of Motifs
6
Creation Date
16-DEC-1995  (UPDATE 06-JUN-1999)
Title
Adenosine receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00553 ADENOSINA2AR; PR00554 ADENOSINA2BR; PR00552 ADENOSINEA1R
PRINTS; PR00555 ADENOSINEA3R
INTERPRO; IPR001634
GCRDB; 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.
 
ADENOSINER is a 6-element fingerprint that provides a signature for the
adenosine receptors. The fingerprint was derived from an initial alignment
of 7 sequences: the motifs were drawn from conserved sections either within
loop or TM regions, focusing on those areas of the alignment that
characterise the adenosine receptors but distinguish them from the rest of
the rhodopsin-like superfamily - motif 1 lies at the N-terminus of the first
TM domain; motif 2 spans part of the first external loop and the N-terminus
of the third TM domain; motif 3 lies at the C-terminus of TM domain 4,
leading into the second external loop; motif 4 spans part of the second
external loop and the N-terminus of TM domain 5; motif 5 spans part of the
third cytoplasmic loop and the N-terminus of TM domain 6; and motif 6 lies
at the N-terminus of TM domain 7. Three iterations on OWL26.3 were required
to reach convergence, at which point a true set comprising 21 sequences was
identified. Four partial matches were also found, all of which are adenosine
receptor fragments.
 
An update on SPTR37_9f identified a true set of 22 sequences.
Summary Information
22 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
6222222222222
5000000
4000000
3000000
2000000
123456
True Positives
AA1R_BOVIN    AA1R_CANFA    AA1R_CAVPO    AA1R_CHICK    
AA1R_HUMAN AA1R_RABIT AA1R_RAT AA2A_CANFA
AA2A_CAVPO AA2A_HUMAN AA2A_MOUSE AA2A_RAT
AA2B_CHICK AA2B_HUMAN AA2B_MOUSE AA2B_RAT
AA3R_CANFA AA3R_HUMAN AA3R_RABIT AA3R_RAT
AA3R_SHEEP 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).
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).
AA2B_CHICK ADENOSINE A2B RECEPTOR - GALLUS GALLUS (CHICKEN).
AA2B_HUMAN ADENOSINE A2B RECEPTOR - HOMO SAPIENS (HUMAN).
AA2B_MOUSE ADENOSINE A2B RECEPTOR - MUS MUSCULUS (MOUSE).
AA2B_RAT ADENOSINE A2B RECEPTOR - RATTUS NORVEGICUS (RAT).
AA3R_CANFA Adenosine A3 receptor - Canis familiaris (Dog).
AA3R_HUMAN Adenosine A3 receptor - Homo sapiens (Human).
AA3R_RABIT Adenosine A3 receptor - Oryctolagus cuniculus (Rabbit).
AA3R_RAT Adenosine A3 receptor (TGPCR1) - Rattus norvegicus (Rat).
AA3R_SHEEP Adenosine A3 receptor - Ovis aries (Sheep).
O08766 A1 RECEPTOR 326 AS - RATTUS NORVEGICUS (RAT).
Scan History
OWL26_3    3  100  NSINGLE    
SPTR37_9f 2 23 NSINGLE
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
SVYITVELAI AA2A_RAT 4 4 -
ALYVALELVI AA2B_HUMAN 8 8 -
ITYITMEAAI RNGPCR 15 15 -
SVYITVELAI A48974 4 4 -
ITYVTMEAAI AA3R_RAT 15 15 -
AAYIGIEVLI AA1R_BOVIN 10 10 -
SVYITVELAI AA2A_HUMAN 7 7 -

Motif 2 width=13
Element Seqn Id St Int Rpt
GCLFLACFVLVLT AA2B_HUMAN 77 59 -
GCLFFACFVLVLT AA2A_RAT 73 59 -
GCLFFACFVLVLT A48974 73 59 -
ACLFMSCVLLVFT RNGPCR 84 59 -
GCLFIACFVLVLT AA2A_HUMAN 76 59 -
TCLKVACPVLILT AA1R_BOVIN 79 59 -
ACLFMSCVLLVFT AA3R_RAT 84 59 -

Motif 3 width=11
Element Seqn Id St Int Rpt
VGLTPMFGWNR RNGPCR 143 46 -
IGLTPMLGWNN A48974 132 46 -
VGLTPMFGWNN AA1R_BOVIN 138 46 -
IGLTPMLGWNN AA2A_HUMAN 135 46 -
IGLTPMLGWNN AA2A_RAT 132 46 -
IGLTPFLGWNS AA2B_HUMAN 136 46 -
VGLTPMFGWNR AA3R_RAT 143 46 -

Motif 4 width=20
Element Seqn Id St Int Rpt
CHFRSVVGLDYMVFFSFITW RNGPCR 168 14 -
CQFEKVISMEYMVYFNFFVW AA1R_BOVIN 169 20 -
CLFEDVVPMNYMVYFNFFAC AA2A_HUMAN 166 20 -
CLFEDVVPMNYMVYYNFFAF AA2A_RAT 161 18 -
CLFENVVPMSYMVYFNFFGC AA2B_HUMAN 171 24 -
CHFRFVVGLDYMVFFSFITW AA3R_RAT 168 14 -
CLFEDVVPMNYMVYYNFFAF A48974 161 18 -

Motif 5 width=14
Element Seqn Id St Int Rpt
RAFYGREFKTAKSL AA3R_RAT 221 33 -
RAFYGREFKTAKSL RNGPCR 221 33 -
RSTLQKEVHAAKSL A48974 217 36 -
QKYYGKELKIAKSL AA1R_BOVIN 223 34 -
RSTLQKEVHAAKSL AA2A_HUMAN 222 36 -
RSTLQKEVHAAKSL AA2A_RAT 217 36 -
RTTLQREIHAAKSL AA2B_HUMAN 223 32 -

Motif 6 width=11
Element Seqn Id St Int Rpt
MCLGILLSHAN RNGPCR 266 31 -
MYLAIILSHSN A48974 265 34 -
IYIAIFLSHGN AA1R_BOVIN 270 33 -
MYLAIVLSHTN AA2A_HUMAN 270 34 -
MYLTIILSHSN AA2A_RAT 265 34 -
MNMAILLSHAN AA2B_HUMAN 272 35 -
MCLGILLSHAN AA3R_RAT 266 31 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
AAYIGIEVLI AA1R_BOVIN 10 10 -
AAYIGIEVLI AA1R_CAVPO 10 10 -
AAYIGIEVLI AA1R_HUMAN 10 10 -
AAYIGIEVLI AA1R_RAT 10 10 -
AAYIGIEVLI O08766 10 10 -
AAYIGIEVLI AA1R_CANFA 10 10 -
AAYIGIEVLI AA1R_RABIT 10 10 -
AAYISIEVLI AA1R_CHICK 10 10 -
SVYITVELAI AA2A_HUMAN 7 7 -
SVYITVELVI AA2A_CAVPO 4 4 -
SVYIMVELAI AA2A_MOUSE 4 4 -
SVYITVELAI AA2A_RAT 4 4 -
WVYITVELAI AA2A_CANFA 7 7 -
TTYIVLELII AA2B_CHICK 6 6 -
ALYVALELVI AA2B_MOUSE 8 8 -
ALYVALELVI AA2B_RAT 8 8 -
ALYVALELVI AA2B_HUMAN 8 8 -
VTYITVEILI AA3R_CANFA 13 13 -
VTYITVEILI AA3R_SHEEP 13 13 -
VTYITMEIFI AA3R_HUMAN 13 13 -
ITYVTMEAAI AA3R_RAT 15 15 -
ASYIVFEIVI AA3R_RABIT 14 14 -

Motif 2 width=13
Element Seqn Id St Int Rpt
TCLKVACPVLILT AA1R_BOVIN 79 59 -
TCLMVACPVLILT AA1R_CAVPO 79 59 -
TCLMVACPVLILT AA1R_HUMAN 79 59 -
TCLMVACPVLILT AA1R_RAT 79 59 -
TCLMVACPVLILT O08766 79 59 -
TCLMVACPVLILT AA1R_CANFA 79 59 -
TCLMVACPVLILT AA1R_RABIT 79 59 -
SCLMMACPVLILT AA1R_CHICK 79 59 -
GCLFIACFVLVLT AA2A_HUMAN 76 59 -
GCLFFACFVLVLT AA2A_CAVPO 73 59 -
GCLFIACFVLVLT AA2A_MOUSE 73 59 -
GCLFFACFVLVLT AA2A_RAT 73 59 -
NCLFFACFVLVLT AA2A_CANFA 76 59 -
SCLFFACFVLVLT AA2B_CHICK 75 59 -
GCLFLACFVLVLT AA2B_MOUSE 77 59 -
SCLFLACFVLVLT AA2B_RAT 77 59 -
GCLFLACFVLVLT AA2B_HUMAN 77 59 -
NCLFMTCLLLIFT AA3R_CANFA 82 59 -
SCLFMTCLMLIFT AA3R_SHEEP 82 59 -
SCLFMTCLLLIFT AA3R_HUMAN 82 59 -
ACLFMSCVLLVFT AA3R_RAT 84 59 -
SCLVMSCLLLVFT AA3R_RABIT 83 59 -

Motif 3 width=11
Element Seqn Id St Int Rpt
VGLTPMFGWNN AA1R_BOVIN 138 46 -
VGLTPMFGWNN AA1R_CAVPO 138 46 -
VGLTPMFGWNN AA1R_HUMAN 138 46 -
VGLTPMFGWNN AA1R_RAT 138 46 -
VGLTPMFGWNN O08766 138 46 -
VGLTPLFGWNR AA1R_CANFA 138 46 -
VGLTPMFGWNN AA1R_RABIT 138 46 -
VGLTPMFGWNN AA1R_CHICK 138 46 -
IGLTPMLGWNN AA2A_HUMAN 135 46 -
IGLTPMLGWNN AA2A_CAVPO 132 46 -
IGLTPMLGWNN AA2A_MOUSE 132 46 -
IGLTPMLGWNN AA2A_RAT 132 46 -
IGLTPMLGWNN AA2A_CANFA 135 46 -
IGLTPLMGWNK AA2B_CHICK 134 46 -
IGLTPFLGWNS AA2B_MOUSE 136 46 -
IGLTPFLGWNS AA2B_RAT 136 46 -
IGLTPFLGWNS AA2B_HUMAN 136 46 -
VGLTPMFGWNM AA3R_CANFA 141 46 -
VGLTPMFGWNM AA3R_SHEEP 141 46 -
VGLTPMFGWNM AA3R_HUMAN 141 46 -
VGLTPMFGWNR AA3R_RAT 143 46 -
VGFTPMFGWNM AA3R_RABIT 142 46 -

Motif 4 width=20
Element Seqn Id St Int Rpt
CQFEKVISMEYMVYFNFFVW AA1R_BOVIN 169 20 -
CEFEKVISMEYMVYFNFFVW AA1R_CAVPO 169 20 -
CEFEKVISMEYMVYFNFFVW AA1R_HUMAN 169 20 -
CEFEKVISMEYMVYFNFFVW AA1R_RAT 169 20 -
CEFEKVISMEYMVYFNFFVW O08766 169 20 -
CEFEKVISMEYMVYFNFFVW AA1R_CANFA 169 20 -
CEFEKVISMEYMVYFNFFVW AA1R_RABIT 169 20 -
CQFETVISMEYMVYFNFFVW AA1R_CHICK 169 20 -
CLFEDVVPMNYMVYFNFFAC AA2A_HUMAN 166 20 -
CLFEDVVPMNYMVYYNFFAF AA2A_CAVPO 163 20 -
CLFEDVVPMNYMVYYNFFAF AA2A_MOUSE 161 18 -
CLFEDVVPMNYMVYYNFFAF AA2A_RAT 161 18 -
CLFEDVVPMNYMVYYNFFAF AA2A_CANFA 166 20 -
CLFENVVTMSYMVYFNFFGC AA2B_CHICK 171 26 -
CLFENVVPMSYMVYFNFFGC AA2B_MOUSE 171 24 -
CLFENVVPMSYMVYFNFFGC AA2B_RAT 171 24 -
CLFENVVPMSYMVYFNFFGC AA2B_HUMAN 171 24 -
CQFSSVMRMDYMVYFSFFTW AA3R_CANFA 166 14 -
CRFRSVMRMDYMVYFSFFLW AA3R_SHEEP 165 13 -
CQFVSVMRMDYMVYFSFLTW AA3R_HUMAN 166 14 -
CHFRFVVGLDYMVFFSFITW AA3R_RAT 168 14 -
CKFDSVIPMEYMVFFSFFTW AA3R_RABIT 167 14 -

Motif 5 width=14
Element Seqn Id St Int Rpt
QKYYGKELKIAKSL AA1R_BOVIN 223 34 -
QKYYGKELKIAKSL AA1R_CAVPO 223 34 -
QKYYGKELKIAKSL AA1R_HUMAN 223 34 -
QKYYGKELKIAKSL AA1R_RAT 223 34 -
QKYYGKELKIAKSL O08766 223 34 -
QKYYGKELKIAKSL AA1R_CANFA 223 34 -
HKYYGKELKIAKSL AA1R_RABIT 223 34 -
QKYYGKELKIAKSL AA1R_CHICK 223 34 -
RSTLQKEVHAAKSL AA2A_HUMAN 222 36 -
RSTLQKEVHPAKSL AA2A_CAVPO 219 36 -
RSTLQKEVHAAKSL AA2A_MOUSE 217 36 -
RSTLQKEVHAAKSL AA2A_RAT 217 36 -
RSTLQKEVHAAKSL AA2A_CANFA 222 36 -
RTTLQKEVHAAKSL AA2B_CHICK 223 32 -
RTTLQREIHAAKSL AA2B_MOUSE 223 32 -
RTTLQREIHAAKSL AA2B_RAT 223 32 -
RTTLQREIHAAKSL AA2B_HUMAN 223 32 -
GAFYGREFKTAKSL AA3R_CANFA 219 33 -
GAFYGREFKTAKSL AA3R_SHEEP 218 33 -
GAFYGREFKTAKSL AA3R_HUMAN 219 33 -
RAFYGREFKTAKSL AA3R_RAT 221 33 -
GAFYRREFKTAKSL AA3R_RABIT 220 33 -

Motif 6 width=11
Element Seqn Id St Int Rpt
IYIAIFLSHGN AA1R_BOVIN 270 33 -
TYIAIFLTHGN AA1R_CAVPO 270 33 -
TYIAIFLTHGN AA1R_HUMAN 270 33 -
IYIAIFLTHGN AA1R_RAT 270 33 -
IYIAIFLTHGN O08766 270 33 -
MYIAIFLTHGN AA1R_CANFA 270 33 -
VYTAIFLTHGN AA1R_RABIT 270 33 -
TYIAIFLTHGN AA1R_CHICK 270 33 -
MYLAIVLSHTN AA2A_HUMAN 270 34 -
MYLTIILSHGN AA2A_CAVPO 267 34 -
MYLAIILSHSN AA2A_MOUSE 265 34 -
MYLTIILSHSN AA2A_RAT 265 34 -
MYLTIVLSHTN AA2A_CANFA 270 34 -
MYVAIILSHAN AA2B_CHICK 272 35 -
MNVAILLSHAN AA2B_MOUSE 272 35 -
MNVAILLSHAN AA2B_RAT 272 35 -
MNMAILLSHAN AA2B_HUMAN 272 35 -
LYLGILLSHAN AA3R_CANFA 264 31 -
LYLGILLSHAN AA3R_SHEEP 263 31 -
LYMGILLSHAN AA3R_HUMAN 264 31 -
MCLGILLSHAN AA3R_RAT 266 31 -
LLVGILLSHAN AA3R_RABIT 265 31 -