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PR00556

Identifier
ADRENRGCA1BR  [View Relations]  [View Alignment]  
Accession
PR00556
No. of Motifs
7
Creation Date
14-AUG-1996  (UPDATE 18-FEB-2000)
Title
Alpha-1B adrenergic receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01103 ADRENERGICR
INTERPRO; IPR001115
GCRDB; GCR_0223; GCR_0530; GCR_0113; GCR_0124; GCR_0518
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]. 
 
Alpha-1B receptor mRNA is distributed widely, high levels occurring in
the CNS (e.g., cerebral cortex and brainstem) and in peripheral tissues
(e.g., the kidney and lung). The receptor is coupled to the phosphoinositide
pathway through a pertussis-toxin-insensitive G protein, probably of the
Gq/G11 class [6]. 
 
ADRENRGCA1BR is a 7-element fingerprint that provides a signature for the
alpha-1B adrenergic receptors. The fingerprint was derived from an initial
alignment of 4 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-1B adrenergic receptors but 
distinguish them from the rest of the rhodopsin-like superfamily - motifs 
1 and 2 lie at the N-terminus; motif 3 lies in the third cytoplasmic loop; 
and motifs 4-7 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-1B 
receptor fragment that lacks the portion of sequence bearing the first
2 motifs.
 
An update on SPTR37_9f identified a true set of 4 sequences.
Summary Information
4 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
74444444
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
A1AB_HUMAN    A1AB_MESAU    A1AB_MOUSE    A1AB_RAT      
Sequence Titles
A1AB_HUMAN  ALPHA-1B ADRENERGIC RECEPTOR (ALPHA 1B-ADRENOCEPTOR) - HOMO SAPIENS (HUMAN). 
A1AB_MESAU ALPHA-1B ADRENERGIC RECEPTOR (ALPHA 1B-ADRENOCEPTOR) - MESOCRICETUS AURATUS (GOLDEN HAMSTER).
A1AB_MOUSE ALPHA-1B ADRENERGIC RECEPTOR (ALPHA 1B-ADRENOCEPTOR) - MUS MUSCULUS (MOUSE).
A1AB_RAT ALPHA-1B ADRENERGIC RECEPTOR (ALPHA 1B-ADRENOCEPTOR) - RATTUS NORVEGICUS (RAT).
Scan History
OWL28_1    1  25   NSINGLE    
SPTR37_9f 2 5 NSINGLE
SPTR37_10f 1 50 NSINGLE
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
DLDTGHNTSAPAQWGELKD A1AB_MESAU 4 4 -
DLDTGHNTSAPAHWGELKN A1AB_HUMAN 4 4 -
DLDTGHNTSAPAHWGELKN JC2332 4 4 -
DLDTGHNTSAPAHWGELKD A1AB_RAT 4 4 -

Motif 2 width=21
Element Seqn Id St Int Rpt
NFTGPNQTSSNSTLPQLDITR A1AB_HUMAN 24 1 -
NFTGPNQTSSNSTLPQLDVTR A1AB_MESAU 24 1 -
NFTGPNQTSSNSTLPQLDITR JC2332 24 1 -
NFTGPNQTSSNSTLPQLDVTR A1AB_RAT 24 1 -

Motif 3 width=18
Element Seqn Id St Int Rpt
NFHEDTLSSTKAKGHNPR A1AB_MESAU 259 214 -
NFHEDTLSSTKAKGHNPR JC2332 259 214 -
NFHEDTLSSTKAKGHNPR A1AB_RAT 259 214 -
NFHEDTLSSTKAKGHNPR A1AB_HUMAN 259 214 -

Motif 4 width=20
Element Seqn Id St Int Rpt
LGACAYTYRPWTRGGSLERS A1AB_RAT 379 102 -
LGGCAYTYRPWTRGGSLERS A1AB_HUMAN 380 103 -
RLGCAYTYRPWTRGGSLERS JC2332 378 101 -
LGACAYTYRPWTRGGSLERS A1AB_MESAU 379 102 -

Motif 5 width=18
Element Seqn Id St Int Rpt
RKDSLDDSGSCLSGSQRT JC2332 400 2 -
RKDSLDDSGSCMSGTQRT A1AB_RAT 401 2 -
RKDSLDDSGSCMSGSQRT A1AB_MESAU 401 2 -
RKDSLDDSGSCLSGSQRT A1AB_HUMAN 402 2 -

Motif 6 width=20
Element Seqn Id St Int Rpt
GYLGRGAPPPVELCAFPEWK A1AB_HUMAN 428 8 -
GYLGRGAPPPVELCAFPEWK JC2332 426 8 -
GYLGRGTQPPVELCAFPEWK A1AB_RAT 427 8 -
GYLGRGAQPPLELCAYPEWK A1AB_MESAU 427 8 -

Motif 7 width=19
Element Seqn Id St Int Rpt
CDTTTDLANGQPGFKSNMP A1AB_RAT 491 44 -
CEAAADVANGQPGFKSNMP A1AB_HUMAN 495 47 -
CDATTDLANGQPGFKSNMP A1AB_MESAU 491 44 -
GCEPRHVANGQPGFKSNMP JC2332 492 46 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
DLDTGHNTSAPAHWGELKD A1AB_MOUSE 4 4 -
DLDTGHNTSAPAHWGELKD A1AB_RAT 4 4 -
DLDTGHNTSAPAQWGELKD A1AB_MESAU 4 4 -
DLDTGHNTSAPAHWGELKN A1AB_HUMAN 4 4 -

Motif 2 width=21
Element Seqn Id St Int Rpt
NFTGPNQTSSNSTLPQLDVTR A1AB_MOUSE 24 1 -
NFTGPNQTSSNSTLPQLDVTR A1AB_RAT 24 1 -
NFTGPNQTSSNSTLPQLDVTR A1AB_MESAU 24 1 -
NFTGPNQTSSNSTLPQLDITR A1AB_HUMAN 24 1 -

Motif 3 width=18
Element Seqn Id St Int Rpt
NFHEDTLSSTKAKGHNPR A1AB_MOUSE 258 213 -
NFHEDTLSSTKAKGHNPR A1AB_RAT 259 214 -
NFHEDTLSSTKAKGHNPR A1AB_MESAU 259 214 -
NFHEDTLSSTKAKGHNPR A1AB_HUMAN 259 214 -

Motif 4 width=20
Element Seqn Id St Int Rpt
LGACAYTYRPWTRGGSLERS A1AB_MOUSE 378 102 -
LGACAYTYRPWTRGGSLERS A1AB_RAT 379 102 -
LGACAYTYRPWTRGGSLERS A1AB_MESAU 379 102 -
LGGCAYTYRPWTRGGSLERS A1AB_HUMAN 380 103 -

Motif 5 width=18
Element Seqn Id St Int Rpt
RKDSLDDSGSCMSGSQRT A1AB_MOUSE 400 2 -
RKDSLDDSGSCMSGTQRT A1AB_RAT 401 2 -
RKDSLDDSGSCMSGSQRT A1AB_MESAU 401 2 -
RKDSLDDSGSCLSGSQRT A1AB_HUMAN 402 2 -

Motif 6 width=20
Element Seqn Id St Int Rpt
GYLGRGTQPPVELCAFPEWK A1AB_MOUSE 426 8 -
GYLGRGTQPPVELCAFPEWK A1AB_RAT 427 8 -
GYLGRGAQPPLELCAYPEWK A1AB_MESAU 427 8 -
GYLGRGAPPPVELCAFPEWK A1AB_HUMAN 428 8 -

Motif 7 width=19
Element Seqn Id St Int Rpt
CDTTTDLANGQPGFKSNMP A1AB_MOUSE 490 44 -
CDTTTDLANGQPGFKSNMP A1AB_RAT 491 44 -
CDATTDLANGQPGFKSNMP A1AB_MESAU 491 44 -
CEAAADVANGQPGFKSNMP A1AB_HUMAN 495 47 -