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PR00568

Identifier
DOPAMINED3R  [View Relations]  [View Alignment]  
Accession
PR00568
No. of Motifs
7
Creation Date
17-AUG-1996  (UPDATE 07-JUN-1999)
Title
Dopamine D3 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00242 DOPAMINER
INTERPRO; IPR001620
GCRDB; GCR_0134; GCR_0221; GCR_0236; GCR_0449; GCR_0936
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. GRANDY, D.K., MARCHIONNI, M.A., MAKAM, H., STOFKO, R.E., ALFANO, M.,
FROTHINGHAM, L., FISCHER, J.B., BURKE-HOWIE, K.J., BUNZOW, J.R.,
SERVER, A.C. AND CIVELLI, O.
Cloning of the cDNA and gene for a human D2 dopamine receptor. 
PROC.NATL.ACAD.SCI.U.S.A. 86 9762-9766 (1989).
 
7. WATSON, S. AND ARKINSTALL, S.
Dopamine.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp96-110.

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]. 
 
Dopamine neurons in the vertebrate central nervous system are involved in
the initiation and execution of movement, the maintenance of emotional
stability, and the regulation of pituitary function [6]. Various human
neurological diseases (e.g., Parkinson disease and schizophrenia), are
believed to be manifestations of dopamine and dopamine receptor imbalance.
The receptors have been divided into several different subtypes (designated
D1-D5), which may be distinguished by their G protein coupling, ligand
specificity, anatomical distribution and physiological effects.
 
D3 receptors have a similar pharmacological profile to D2 receptors. They
are expressed predominantly in the limbic area (including the olfactory
tubercle, nucleus accumbens, islands of Calleja and hypothalamus), and they
are present in lower levels in the caudate-putamen and cerebral cortex [7].
The receptors are also found in dopamine cell bodies in the substantia
nigra [7]. The distribution of the receptors is consistent with a role in
cognition and emotional functions; they may thus be the target of anti-
psychotic therapy involving dopamine antagonists [7]. 
 
DOPAMINED3R is a 7-element fingerprint that provides a signature for the
D3 family of dopamine receptors. The fingerprint was derived from an initial
alignment of 6 sequences: the motifs were drawn from conserved sections
within either loop or N-terminal regions, focusing on those areas of the
alignment that characterise the D3 receptors but distinguish them from the
rest of the rhodopsin-like superfamily - motif 1 lies at the N-terminus;
motif 2 spans the second cytoplasmic loop, leading into the N-terminus of
TM domain 4; motifs 3-6 span the third cytoplasmic loop; and motif 7 spans
the third external loop, leading into the N-terminus of TM domain 7. 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, A48258 and A55419, both of which are D3 receptor fragments.
 
An update on SPTR37_9f identified a true set of 5 sequences.
Summary Information
5 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
75555555
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
D3DR_CERAE    D3DR_HUMAN    D3DR_MOUSE    D3DR_RAT      
Q13167
Sequence Titles
D3DR_CERAE  D(3) DOPAMINE RECEPTOR - CERCOPITHECUS AETHIOPS (GREEN MONKEY) (GRIVET). 
D3DR_HUMAN D(3) DOPAMINE RECEPTOR - HOMO SAPIENS (HUMAN).
D3DR_MOUSE D(3) DOPAMINE RECEPTOR - MUS MUSCULUS (MOUSE).
D3DR_RAT D(3) DOPAMINE RECEPTOR - RATTUS NORVEGICUS (RAT).
Q13167 DOPAMINE D3 RECEPTOR - HOMO SAPIENS (HUMAN).
Scan History
OWL28_1    1  50   NSINGLE    
SPTR37_9f 2 6 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
HLNSTCGAENSTGVNRARPH D3DR_RAT 10 10 -
HINSTCGAENSTGVNRARPH D3DR_MOUSE 10 10 -
HLNYTCGAENSTGASQARPH D3DR_HUMAN 10 10 -
HLNYTCGAENSTGASQARPH HSU25441 10 10 -
HLNYTCGVENSTGASQARPH CAU21307 10 10 -
HLNSTCGAENSTGVNRARPH RATD3A06 10 10 -

Motif 2 width=20
Element Seqn Id St Int Rpt
VHYQHGTGQSSCRRVTLMIT CAU21307 136 106 -
VHYEHGTGQSSCRRVALMIT RATD3A06 136 106 -
VHYQHGTGQSSCRRVALMIT HSU25441 135 105 -
VHYQHGTGQSSCRRVALMIT D3DR_HUMAN 136 106 -
VHYQHGTGQSSCRRVALMIT D3DR_MOUSE 136 106 -
VHYQHGTGQSSCRRVALMIT D3DR_RAT 136 106 -

Motif 3 width=17
Element Seqn Id St Int Rpt
RILTRQNSQCNSVRPGF CAU21307 222 66 -
RILTRQNSQCISIRPGF D3DR_RAT 222 66 -
RILTRQNSQCISIRPGF D3DR_MOUSE 222 66 -
RILTRQNSQCNSVRPGF D3DR_HUMAN 222 66 -
RILTRQNSQCISIRPGF RATD3A06 230 74 -
RILTRQNSQCNSVRPGF HSU25441 221 66 -

Motif 4 width=16
Element Seqn Id St Int Rpt
HLELKRYYSICQDTAL CAU21307 249 10 -
HLELKRYYSICQDTAL D3DR_HUMAN 249 10 -
HGELKRYYSICQDTAL D3DR_MOUSE 296 57 -
HGGLKRYYSICQDTAL D3DR_RAT 296 57 -
HGGLKRYYSICQDTAL RATD3A06 304 57 -
HLELKRYYSICQDTAL HSU25441 248 10 -

Motif 5 width=19
Element Seqn Id St Int Rpt
TRNSLSPTMAPKLSLEVRK D3DR_MOUSE 328 16 -
TRNSLSPTMAPKLSLEVRK D3DR_RAT 328 16 -
TRNSLSPTMAPKLSLEVRK RATD3A06 336 16 -
TRNSLSPTIAPKLSLEVRK D3DR_HUMAN 282 17 -
TRNSLSPTIAPKLSLEVRK CAU21307 282 17 -
TRNSLSPTIAPKLSLEVRK HSU25441 281 17 -

Motif 6 width=21
Element Seqn Id St Int Rpt
LSNGRLSTSLKLGPLQPRGVP HSU25441 300 0 -
LSNGRLSTSLRLGPLQPRGVP RATD3A06 355 0 -
LSNGRLSTSLKLGPLQPRGVP D3DR_MOUSE 347 0 -
LSNGRLSTSLRLGPLQPRGVP D3DR_RAT 347 0 -
LSNGRLSTSLKLGPLQPRGVP D3DR_HUMAN 301 0 -
LSNGRLSTSLKLGPLQPRGVP CAU21307 301 0 -

Motif 7 width=14
Element Seqn Id St Int Rpt
HCQTCHVSPELYSA D3DR_HUMAN 354 32 -
HCQTCHVSPELYSA HSU25441 353 32 -
HCQTCHVSPELYSA CAU21307 354 32 -
HCQACHVSPELYRA RATD3A06 408 32 -
HCQACHVSPELYRA D3DR_RAT 400 32 -
HCQACHVSPELYRA D3DR_MOUSE 400 32 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
HLNYTCGAENSTGASQARPH D3DR_HUMAN 10 10 -
HLNYTCGAENSTGASQARPH Q13167 10 10 -
HLNYTCGVENSTGASQARPH D3DR_CERAE 10 10 -
HINSTCGAENSTGVNRARPH D3DR_MOUSE 10 10 -
HLNSTCGAENSTGVNRARPH D3DR_RAT 10 10 -

Motif 2 width=20
Element Seqn Id St Int Rpt
VHYQHGTGQSSCRRVALMIT D3DR_HUMAN 136 106 -
VHYQHGTGQSSCRRVALMIT Q13167 135 105 -
VHYQHGTGQSSCRRVTLMIT D3DR_CERAE 136 106 -
VHYQHGTGQSSCRRVALMIT D3DR_MOUSE 136 106 -
VHYQHGTGQSSCRRVALMIT D3DR_RAT 136 106 -

Motif 3 width=17
Element Seqn Id St Int Rpt
RILTRQNSQCNSVRPGF D3DR_HUMAN 222 66 -
RILTRQNSQCNSVRPGF Q13167 221 66 -
RILTRQNSQCNSVRPGF D3DR_CERAE 222 66 -
RILTRQNSQCISIRPGF D3DR_MOUSE 222 66 -
RILTRQNSQCISIRPGF D3DR_RAT 222 66 -

Motif 4 width=16
Element Seqn Id St Int Rpt
HLELKRYYSICQDTAL D3DR_HUMAN 249 10 -
HLELKRYYSICQDTAL Q13167 248 10 -
HLELKRYYSICQDTAL D3DR_CERAE 249 10 -
HGELKRYYSICQDTAL D3DR_MOUSE 296 57 -
HGGLKRYYSICQDTAL D3DR_RAT 296 57 -

Motif 5 width=19
Element Seqn Id St Int Rpt
TRNSLSPTIAPKLSLEVRK D3DR_HUMAN 282 17 -
TRNSLSPTIAPKLSLEVRK Q13167 281 17 -
TRNSLSPTIAPKLSLEVRK D3DR_CERAE 282 17 -
TRNSLSPTMAPKLSLEVRK D3DR_MOUSE 328 16 -
TRNSLSPTMAPKLSLEVRK D3DR_RAT 328 16 -

Motif 6 width=21
Element Seqn Id St Int Rpt
LSNGRLSTSLKLGPLQPRGVP D3DR_HUMAN 301 0 -
LSNGRLSTSLKLGPLQPRGVP Q13167 300 0 -
LSNGRLSTSLKLGPLQPRGVP D3DR_CERAE 301 0 -
LSNGRLSTSLKLGPLQPRGVP D3DR_MOUSE 347 0 -
LSNGRLSTSLRLGPLQPRGVP D3DR_RAT 347 0 -

Motif 7 width=14
Element Seqn Id St Int Rpt
HCQTCHVSPELYSA D3DR_HUMAN 354 32 -
HCQTCHVSPELYSA Q13167 353 32 -
HCQTCHVSPELYSA D3DR_CERAE 354 32 -
HCQACHVSPELYRA D3DR_MOUSE 400 32 -
HCQACHVSPELYRA D3DR_RAT 400 32 -