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PR00560

Identifier
ADRENRGCA2CR  [View Relations]  [View Alignment]  
Accession
PR00560
No. of Motifs
6
Creation Date
15-AUG-1996  (UPDATE 10-JUN-1999)
Title
Alpha-2C adrenergic receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01103 ADRENERGICR
INTERPRO; IPR000735
GCRDB; GCR_0114; GCR_0153; GCR_0538; GCR_0044; GCR_0425; GCR_0440

GCRDB; GCR_0484
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]. 
 
Northern analysis has demonstrated the presence of alpha-2C receptor mRNA
in rat brain (including the cerebral cortex, cerebellum, hippocampus and
brainstem), but not in peripheral tissues [6]. The receptor inhibits
adenylyl cyclase through a pertussis-toxin-insensitive G protein belonging
to the Gi/G0 class [6]. 
 
ADRENRGCA2CR is a 6-element fingerprint that provides a signature for the
alpha-2C adrenergic receptors. The fingerprint was derived from an initial
alignment of 9 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-2C adrenergic receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motifs 
1 and 2 span the N-terminus, leading into the N-terminal half of TM domain
1; motifs 3 and 4 lie in the third cytoplasmic loop; motif 5 spans the third
external loop; and motif 6 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,
A2AC_DIDMA and LOU07743, both of which are alpha-2 adrenergic receptors
whose sequences are significantly different from those of the rest of the
alpha-2C receptor family.
 
An update on SPTR37_9f identified a true set of 5 sequences, and 2
partial matches.
Summary Information
   5 codes involving  6 elements
1 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
6555555
5011111
4000000
3000000
2010100
123456
True Positives
A2AC_CAVPO    A2AC_HUMAN    A2AC_MOUSE    A2AC_RAT      
A2AD_HUMAN
True Positive Partials
Codes involving 5 elements
A2AC_DIDMA
Codes involving 2 elements
A2AR_LABOS
Sequence Titles
A2AC_CAVPO  ALPHA-2C ADRENERGIC RECEPTOR (ALPHA-2C ADRENOCEPTOR) - CAVIA PORCELLUS (GUINEA PIG). 
A2AC_HUMAN ALPHA-2C-1 ADRENERGIC RECEPTOR (ALPHA-2C-1 ADRENOCEPTOR) (SUBTYPE C4) - HOMO SAPIENS (HUMAN).
A2AC_MOUSE ALPHA-2C ADRENERGIC RECEPTOR (ALPHA-2C ADRENOCEPTOR) (SUBTYPE C4) - MUS MUSCULUS (MOUSE).
A2AC_RAT ALPHA-2C ADRENERGIC RECEPTOR (ALPHA-2C ADRENOCEPTOR) (SUBTYPE C4) - RATTUS NORVEGICUS (RAT).
A2AD_HUMAN ALPHA-2C-2 ADRENERGIC RECEPTOR (ALPHA-2C-2 ADRENOCEPTOR) - HOMO SAPIENS (HUMAN).

A2AC_DIDMA ALPHA-2C ADRENERGIC RECEPTOR (ALPHA-2C ADRENOCEPTOR) - DIDELPHIS MARSUPIALIS VIRGINIANA (NORTH AMERICAN OPOSSUM).

A2AR_LABOS ALPHA-2 ADRENERGIC RECEPTOR (ALPHA-2 ADRENOCEPTOR) - LABRUS OSSIFAGUS (CUCKOO WRASSE).
Scan History
OWL28_1    1  50   NSINGLE    
SPTR37_9f 2 22 NSINGLE
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
GGGANASGTDWGPPPGQY A2AC_RAT 29 29 -
GGGANASGTDWGPPPGQY RATA2AR 29 29 -
GGGVNASGAVWGPPPSQY CPU25724 25 25 -
GGGANASGTDWAPPPGQY RATA2BADR 29 29 -
GGGANASGTDWVPPPGQY A48392 29 29 -
GGGANASGTDWGPPPGQY RATRG10 29 29 -
GGVANASGASWGPPRGQY A2AC_HUMAN 29 29 -
GGGANASGTDWVPPPGQY A2AC_MOUSE 29 29 -
GGVANASGASWGPPRGQY A2AD_HUMAN 29 29 -

Motif 2 width=16
Element Seqn Id St Int Rpt
YSAGAVAGLAAVVGFL A2AC_MOUSE 46 -1 -
YSAGAVAGLAAVVGFL A2AC_HUMAN 46 -1 -
YSAGAVAGLAAVVGFL RATRG10 46 -1 -
YSAGAVAGLAAVVGFL A48392 46 -1 -
YSAGAVAGLAAVVGFL RATA2BADR 46 -1 -
YSAGAVAGLAAVVGFL CPU25724 42 -1 -
YSAGAVAGLAAVVGFL RATA2AR 46 -1 -
YSAGAVAGLAAVVGFL A2AC_RAT 46 -1 -
YSAGAVAGLAAVVGFL A2AD_HUMAN 46 -1 -

Motif 3 width=20
Element Seqn Id St Int Rpt
SPGPGGRLSRASSRSVEFFL RATA2BADR 334 272 -
SPGPGGRLSRASSRSVEFFL A48392 334 272 -
SPGPGGRLSRASSRSVEFFL RATRG10 334 272 -
SPGPGGRLSRASSRSVEFFL A2AC_HUMAN 337 275 -
SPGPGGRLSRASSRSVEFFL A2AC_MOUSE 334 272 -
SPGPGGRLSRASSRSVEFFL A2AD_HUMAN 334 272 -
SPGPGGRLSRASSRSVEFFL A2AC_RAT 334 272 -
SPGPGGRLSRASSRSVEFFL RATA2AR 334 272 -
SPGPGGRLSRASSRSVEFFL CPU25724 331 273 -

Motif 4 width=20
Element Seqn Id St Int Rpt
SRRRRARSSVCRRKVAQARE A48392 354 0 -
SRRRRARSSVCRRKVAQARE CPU25724 351 0 -
SRRRRARSSVCRRKVAQARE A2AC_HUMAN 357 0 -
SRRRRARSSVCRRKVAQARE A2AC_MOUSE 354 0 -
SRRRRARSSVCRRKVAQARE A2AD_HUMAN 354 0 -
SRRRRARSSVCRRKVAQARE A2AC_RAT 354 0 -
SRRRRARSSVCRRKVAQARE RATA2AR 354 0 -
SRRRRARSSVCRRKVAQARE RATRG10 354 0 -
SRRRRARSSVCRRKVAQARE RATA2BADR 354 0 -

Motif 5 width=13
Element Seqn Id St Int Rpt
LYGICREACQVPG A2AD_HUMAN 400 26 -
LYGICREACQLPE RATA2AR 400 26 -
LYGICREACQLPE RATRG10 400 26 -
LYGICREACQLPE A48392 400 26 -
LYGICREACQLPE RATA2BADR 400 26 -
LYGICREACQLPT CPU25724 397 26 -
LYGICREACQLPE A2AC_RAT 400 26 -
LYGICREACQLPE A2AC_MOUSE 400 26 -
LYGICREACQVPG A2AC_HUMAN 403 26 -

Motif 6 width=16
Element Seqn Id St Int Rpt
RRSFKHILFRRRRRGF RATRG10 441 28 -
RRSFKHILFRRRRRGF A2AD_HUMAN 441 28 -
RRSFKHILFRRRRRGF RATA2AR 441 28 -
RRSFKHILFRRRRRGF A2AC_MOUSE 441 28 -
RPSFKHILFRRRRRGF A2AC_HUMAN 444 28 -
RRSFKHILFRRRRRGF A2AC_RAT 441 28 -
RRSFKHILFRRRRRGF CPU25724 438 28 -
RRSFKHILFRRRRRGF RATA2BADR 441 28 -
RRSFKHILFRRRRRGF A48392 441 28 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
GGGANASGTDWGPPPGQY A2AC_RAT 29 29 -
GGVANASGASWGPPRGQY A2AD_HUMAN 29 29 -
GGGANASGTDWVPPPGQY A2AC_MOUSE 29 29 -
GGVANASGASWGPPRGQY A2AC_HUMAN 29 29 -
GGGVNASGAVWGPPPSQY A2AC_CAVPO 25 25 -

Motif 2 width=16
Element Seqn Id St Int Rpt
YSAGAVAGLAAVVGFL A2AC_RAT 46 -1 -
YSAGAVAGLAAVVGFL A2AD_HUMAN 46 -1 -
YSAGAVAGLAAVVGFL A2AC_MOUSE 46 -1 -
YSAGAVAGLAAVVGFL A2AC_HUMAN 46 -1 -
YSAGAVAGLAAVVGFL A2AC_CAVPO 42 -1 -

Motif 3 width=20
Element Seqn Id St Int Rpt
SPGPGGRLSRASSRSVEFFL A2AC_RAT 334 272 -
SPGPGGRLSRASSRSVEFFL A2AD_HUMAN 334 272 -
SPGPGGRLSRASSRSVEFFL A2AC_MOUSE 334 272 -
SPGPGGRLSRASSRSVEFFL A2AC_HUMAN 337 275 -
SPGPGGRLSRASSRSVEFFL A2AC_CAVPO 331 273 -

Motif 4 width=20
Element Seqn Id St Int Rpt
SRRRRARSSVCRRKVAQARE A2AC_RAT 354 0 -
SRRRRARSSVCRRKVAQARE A2AD_HUMAN 354 0 -
SRRRRARSSVCRRKVAQARE A2AC_MOUSE 354 0 -
SRRRRARSSVCRRKVAQARE A2AC_HUMAN 357 0 -
SRRRRARSSVCRRKVAQARE A2AC_CAVPO 351 0 -

Motif 5 width=13
Element Seqn Id St Int Rpt
LYGICREACQLPE A2AC_RAT 400 26 -
LYGICREACQVPG A2AD_HUMAN 400 26 -
LYGICREACQLPE A2AC_MOUSE 400 26 -
LYGICREACQVPG A2AC_HUMAN 403 26 -
LYGICREACQLPT A2AC_CAVPO 397 26 -

Motif 6 width=16
Element Seqn Id St Int Rpt
RRSFKHILFRRRRRGF A2AC_RAT 441 28 -
RRSFKHILFRRRRRGF A2AD_HUMAN 441 28 -
RRSFKHILFRRRRRGF A2AC_MOUSE 441 28 -
RPSFKHILFRRRRRGF A2AC_HUMAN 444 28 -
RRSFKHILFRRRRRGF A2AC_CAVPO 438 28 -