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PR00557

Identifier
ADRENRGCA1AR  [View Relations]  [View Alignment]  
Accession
PR00557
No. of Motifs
6
Creation Date
14-AUG-1996  (UPDATE 18-FEB-2000)
Title
Alpha-1A adrenergic receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01103 ADRENERGICR
INTERPRO; IPR001004
GCRDB; GCR_0542; GCR_0802; GCR_0004
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, S.
Adrenaline and noradrenaline.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp32-54.

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 the periphery, the adrenergic system plays an important role in
regulating the cardiovascular system [6]. Increased sympathetic discharge
to the heart increases the rate and force of contraction mediated through 
beta-1 receptors. Circulating adrenaline also acts on cardiac tissue, and, 
in addition acts both on alpha-1 adrenoceptors in arterial smooth muscle, 
stimulating vasoconstriction, and on beta-2 adrenoceptors in vascular beds 
of skeletal muscle, stimulating vasodilation [6]. In the CNS, noradrenaline 
is thought to be involved in the regulation of mood, and various psycho-
active drugs alter noradrenergic function. Numerous drugs exert their 
actions via adrenoceptors: e.g., beta-2 selective agonists such as 
salbutamol are used in the acute treatment of asthma, while alpha agonists 
prolong the action of local anaesthetics, and act as nasal decongestants [6].
 
Adrenoceptors can be divided into three main classes based on sequence
similarity, receptor pharmacology and signalling mechanisms. Further 
subdivisions exist within each class [6]. A large number of agonists and 
antagonists distinguish between the different classes of adrenoceptor; by
contrast, relatively small differences in agonist and antagonist affinities
are demonstrated, especially within the alpha-1 and alpha-2 adrenoceptor
subtypes [6]. 
 
The alpha-1A receptor has not been detected in rat or bovine tissues by
Northern analysis [6]. Its expression is thus either very low, or highly
specialised in tissue distribution [6]. The receptor is coupled to the 
phosphoinositide pathway through a pertussis-toxin-insensitive G protein, 
probably of the Gq/G11 class [6]. 
 
ADRENRGCA1AR is a 6-element fingerprint that provides a signature for the
alpha-1A adrenergic receptors. The fingerprint was derived from an initial
alignment of 8 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 alpha-1A adrenergic receptors but 
distinguish them from the rest of the rhodopsin-like superfamily - motif 
1 lies at the N-terminus; motifs 2 and 3 lie in the third cytoplasmic loop; 
and motifs 4-6 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, an alpha-1C 
receptor fragment that matches motifs 2 and 3.
 
An update on SPTR37_9f identified a true set of 8 sequences.
Summary Information
8 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
6888888
5000000
4000000
3000000
2000000
123456
True Positives
A1AA_BOVIN    A1AA_HUMAN    A1AA_RABIT    A1AA_RAT      
O54913 O60451 Q13675 Q13729
Sequence Titles
A1AA_BOVIN  ALPHA-1A ADRENERGIC RECEPTOR (ALPHA 1A-ADRENOCEPTOR) (ALPHA-1C ADRENERGIC RECEPTOR) - BOS TAURUS (BOVINE). 
A1AA_HUMAN ALPHA-1A ADRENERGIC RECEPTOR (ALPHA 1A-ADRENOCEPTOR) (ALPHA-1C ADRENERGIC RECEPTOR) - HOMO SAPIENS (HUMAN).
A1AA_RABIT ALPHA-1A ADRENERGIC RECEPTOR (ALPHA 1A-ADRENOCEPTOR) (ALPHA-1C ADRENERGIC RECEPTOR) - ORYCTOLAGUS CUNICULUS (RABBIT).
A1AA_RAT ALPHA-1A ADRENERGIC RECEPTOR (ALPHA 1A-ADRENOCEPTOR) (ALPHA-1C ADRENERGIC RECEPTOR) - RATTUS NORVEGICUS (RAT).
O54913 ALPHA 1A-ADRENERGIC RECEPTOR - MUS MUSCULUS (MOUSE).
O60451 ALPHA 1A ADRENERGIC RECEPTOR ISOFORM 4 - HOMO SAPIENS (HUMAN).
Q13675 ALPHA 1C ADRENERGIC RECEPTOR ISOFORM 2 - HOMO SAPIENS (HUMAN).
Q13729 ALPHA 1C ADRENERGIC RECEPTOR ISOFORM 3 - HOMO SAPIENS (HUMAN).
Scan History
OWL28_1    1  50   NSINGLE    
SPTR37_9f 2 9 NSINGLE
Initial Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
FLSGNASDSSNCTQPPAPVNISK A1AC_HUMAN 3 3 -
FLSGNASDSSNCTQPPAPVNISK JN0765 3 3 -
FLSGNASDSSNCTQPPAPVNISK JC2333 3 3 -
FLSGNASDSSNCTQPPAPVNISK HSU02569 3 3 -
FLSGNASDSSNCTQPPAPVNISK HUMA1CAR2 3 3 -
FLSGNASDSSNCTHPPPPVNISK A1AC_BOVIN 3 3 -
LLSENASEGSNCTHPPAPVNISK A1AC_RAT 3 3 -
LLSENASEGSNCTHPPAPVNISK RNU13368 3 3 -

Motif 2 width=16
Element Seqn Id St Int Rpt
KSGLKTDKSDSEQVTL A1AC_HUMAN 219 193 -
KSGLKTDKSDSEQVTL JN0765 219 193 -
KSGLKTDKSDSEQVTL JC2333 219 193 -
KSGLKTDKSDSEQVTL HSU02569 219 193 -
KSGLKTDKSDSEQVTL HUMA1CAR2 219 193 -
KSGLKTDKSDSEQVTL A1AC_BOVIN 219 193 -
KSGLKTDKSDSEQVTL A1AC_RAT 219 193 -
KSGLKTDKSDSEQVTL RNU13368 219 193 -

Motif 3 width=18
Element Seqn Id St Int Rpt
RKNAPAGGSGMASAKTKT A1AC_HUMAN 238 3 -
RKNAPAGGSGMASAKTKT JN0765 238 3 -
RKNAPAGGSGHASAKTKT JC2333 238 3 -
RKNAPAGGSGMASAKTKT HSU02569 238 3 -
RKNAPAGGSGMASAKTKT HUMA1CAR2 238 3 -
RKNAQVGGSGVTSAKNKT A1AC_BOVIN 238 3 -
RKNVPAEGGGVSSAKNKT A1AC_RAT 238 3 -
RKNVPAEGGGVSSAKNKT RNU13368 238 3 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LGYTLHPPSQAVEGQHKD A1AC_HUMAN 356 100 -
LGYTLHPPSQAVEGQHKD JN0765 356 100 -
LGYTLHPPSQAVEGQHKD JC2333 356 100 -
LGYPLHPPSQAVEGQHKD HSU02569 356 100 -
LGYTLHPPSQAVEGQHKD HUMA1CAR2 356 100 -
LGYTLHAPSHVLEGQHKD A1AC_BOVIN 356 100 -
LGYTLHPPSQALEGQHRD A1AC_RAT 356 100 -
LGYTLHPPSQALEGQHRD RNU13368 356 100 -

Motif 5 width=20
Element Seqn Id St Int Rpt
RIPVGSRETFYRISKTDGVC A1AC_HUMAN 376 2 -
RIPVGSRETFYRISKTDGVC JN0765 376 2 -
RIPVGSRETFYRISKTDGVC JC2333 376 2 -
RIPVGSRETFYRISKTDGVC HSU02569 376 2 -
RIPVGSRETFYRISKTDGVC HUMA1CAR2 376 2 -
RIPVGSAETFYKISKTDGVC A1AC_BOVIN 376 2 -
RIPVGSGETFYKISKTDGVC A1AC_RAT 376 2 -
RIPVGSGETFYKISKTDGVC RNU13368 376 2 -

Motif 6 width=20
Element Seqn Id St Int Rpt
FSSMPRGSARITVSKDQSSC A1AC_HUMAN 400 4 -
FSSMPRGSARITVSKDQSSC JN0765 400 4 -
FSSMPRGSARITVSKDQSSC JC2333 400 4 -
FSSMPRGSARITVSKDQSSC HSU02569 400 4 -
FSSMPRGSARITVSKDQSSC HUMA1CAR2 400 4 -
FSSLPRGSARMAVARDPSAC A1AC_BOVIN 400 4 -
FSSMPQGSARITVPKDQSAC A1AC_RAT 400 4 -
FSSMPQGSARITVPKDQSAC RNU13368 400 4 -
Final Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
FLSGNASDSSNCTQPPAPVNISK A1AA_HUMAN 3 3 -
FLSGNASDSSNCTQPPAPVNISK Q13729 3 3 -
FLSGNASDSSNCTQPPAPVNISK Q13675 3 3 -
FLSGNASDSSNCTQPPAPVNISK O60451 3 3 -
FLSGNASDSSNCTHPPAPVNISK A1AA_RABIT 3 3 -
LLSENASEGSNCTHPPAPVNISK A1AA_RAT 3 3 -
LLSENASEGSNCTHPPAQVNISK O54913 3 3 -
FLSGNASDSSNCTHPPPPVNISK A1AA_BOVIN 3 3 -

Motif 2 width=16
Element Seqn Id St Int Rpt
KSGLKTDKSDSEQVTL A1AA_HUMAN 219 193 -
KSGLKTDKSDSEQVTL Q13729 219 193 -
KSGLKTDKSDSEQVTL Q13675 219 193 -
KSGLKTDKSDSEQVTL O60451 219 193 -
KSGLKTDKSDSEQVTL A1AA_RABIT 219 193 -
KSGLKTDKSDSEQVTL A1AA_RAT 219 193 -
KSGLKTDKSDSEQVTL O54913 219 193 -
KSGLKTDKSDSEQVTL A1AA_BOVIN 219 193 -

Motif 3 width=18
Element Seqn Id St Int Rpt
RKNAPAGGSGMASAKTKT A1AA_HUMAN 238 3 -
RKNAPAGGSGMASAKTKT Q13729 238 3 -
RKNAPAGGSGMASAKTKT Q13675 238 3 -
RKNAPAGGSGMASAKTKT O60451 238 3 -
RKNAPAGGSGVASAKNKT A1AA_RABIT 238 3 -
RKNVPAEGGGVSSAKNKT A1AA_RAT 238 3 -
RKNVPAEGSGVSSAKNKT O54913 238 3 -
RKNAQVGGSGVTSAKNKT A1AA_BOVIN 238 3 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LGYTLHPPSQAVEGQHKD A1AA_HUMAN 356 100 -
LGYTLHPPSQAVEGQHKD Q13729 356 100 -
LGYTLHPPSQAVEGQHKD Q13675 356 100 -
LGYTLHPPSQAVEGQHKD O60451 356 100 -
LGYTLHAPSQALEGQHKD A1AA_RABIT 356 100 -
LGYTLHPPSQALEGQHRD A1AA_RAT 356 100 -
LGYTLHPPSQAVEEQHRG O54913 356 100 -
LGYTLHAPSHVLEGQHKD A1AA_BOVIN 356 100 -

Motif 5 width=20
Element Seqn Id St Int Rpt
RIPVGSRETFYRISKTDGVC A1AA_HUMAN 376 2 -
RIPVGSRETFYRISKTDGVC Q13729 376 2 -
RIPVGSRETFYRISKTDGVC Q13675 376 2 -
RIPVGSRETFYRISKTDGVC O60451 376 2 -
RIPVGSGETFYKISKTDGVC A1AA_RABIT 376 2 -
RIPVGSGETFYKISKTDGVC A1AA_RAT 376 2 -
RIPVGSGETFYKISKTDGVC O54913 376 2 -
RIPVGSAETFYKISKTDGVC A1AA_BOVIN 376 2 -

Motif 6 width=20
Element Seqn Id St Int Rpt
FSSMPRGSARITVSKDQSSC A1AA_HUMAN 400 4 -
FSSMPRGSARITVSKDQSSC Q13729 400 4 -
FSSMPRGSARITVSKDQSSC Q13675 400 4 -
FSSMPRGSARITVSKDQSSC O60451 400 4 -
FSSMPRGSARITVPKDQSAC A1AA_RABIT 400 4 -
FSSMPQGSARITVPKDQSAC A1AA_RAT 400 4 -
FSSMPQGSARITMPKDQSAC O54913 400 4 -
FSSLPRGSARMAVARDPSAC A1AA_BOVIN 400 4 -