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PR00569

Identifier
DOPAMINED4R  [View Relations]  [View Alignment]  
Accession
PR00569
No. of Motifs
3
Creation Date
17-AUG-1996  (UPDATE 30-JUN-2009)
Title
Dopamine D4 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00242 DOPAMINER
INTERPRO; IPR002185
MIM; 126452
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, 1994, PP.96-110.

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 [1,2]. 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.
 
D4 receptors have a similar pharmacological profile to D2 receptors. They
are expressed in the brain, predominantly in the medulla, amgdala, midbrain
and frontal cortex; lower levels are found in the striatum and olfactory
tubercle [7]. D4 receptor mRNA has also been detected in peripheral tissues,
and the protein appears to be expressed preferentially in the cardiovascular
system in the rat [7]. They inhibit adenylyl cyclase through a pertussis-
toxin-sensitive G protein, probably belonging to the Gi/Go class [7]. 
 
DOPAMINED4R is a 3-element fingerprint that provides a signature for the
dopamine D4 receptors. The fingerprint was derived from an initial
alignment of 7 sequences: the motifs were drawn from conserved sections,
focusing on those areas of the alignment that characterise the D4 receptors
but distinguish them from the rest of the rhodopsin-like superfamily - 
motif 1 lies in the first extracellular loop; motif 2 resides in the second
extracellular loop; and motif 3 lies in the third cytoplasmic loop. Two
iterations on SPTR57_40f were required to reach convergence, at which point 
a true set comprising 13 sequences was identified. Two partial matches were
also found, O42321_CYPCA and Q5DJ15_DANRE, which are translated carp and
zebrafish mRNAs that fail to make signficant matches with motif 1 and with
motif 3, respectively.
Summary Information
  13 codes involving  3 elements
2 codes involving 2 elements
Composite Feature Index
3131313
2121
123
True Positives
A5GXL4_PARMJ  B0M0J7_HUMAN  B6UVA0_CHICK  D4DR_HUMAN    
D4DR_MOUSE D4DR_RAT DRD4_MUSPF O42322
Q4SUF1_TETNG Q5DJ14_DANRE Q5DJ16_DANRE Q7TT80_MOUSE
Q8NGM5_HUMAN
True Positive Partials
Codes involving 2 elements
O42321 Q5DJ15_DANRE
Sequence Titles
A5GXL4_PARMJ Dopamine receptor D4 - Parus major (Great tit). 
B0M0J7_HUMAN Dopamine receptor D4 - Homo sapiens (Human).
B6UVA0_CHICK DRD4 - Gallus gallus (Chicken).
D4DR_HUMAN D(4) DOPAMINE RECEPTOR (D(2C) DOPAMINE RECEPTOR) - HOMO SAPIENS (HUMAN).
D4DR_MOUSE D(4) DOPAMINE RECEPTOR (D(2C) DOPAMINE RECEPTOR) - MUS MUSCULUS (MOUSE).
D4DR_RAT D(4) DOPAMINE RECEPTOR (D(2C) DOPAMINE RECEPTOR) - RATTUS NORVEGICUS (RAT).
DRD4_MUSPF D(4) dopamine receptor - Mustela putorius furo (European domestic ferret) (Mustela furo).
O42322 D4B DOPAMINE RECEPTOR - CYPRINUS CARPIO (COMMON CARP).
Q4SUF1_TETNG Chromosome undetermined SCAF13960, whole genome shotgun sequence - Tetraodon nigroviridis (Green puffer).
Q5DJ14_DANRE Dopamine D4c receptor - Danio rerio (Zebrafish) (Brachydanio rerio).
Q5DJ16_DANRE Dopamine D4a receptor - Danio rerio (Zebrafish) (Brachydanio rerio).
Q7TT80_MOUSE Dopamine receptor 4 - Mus musculus (Mouse).
Q8NGM5_HUMAN Seven transmembrane helix receptor - Homo sapiens (Human).

O42321 D4A DOPAMINE RECEPTOR - CYPRINUS CARPIO (COMMON CARP).
Q5DJ15_DANRE Dopamine D4b receptor - Danio rerio (Zebrafish) (Brachydanio rerio).
Scan History
SPTR57_40f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
GGVWLLSPRLC D4DR_RAT 95 95 -
GGAWLLSPRLC D4DR_HUMAN 98 98 -
GGVWSLSTVLC A5GXL4_PARMJ 80 80 -
GGVWSLSTVLC B6UVA0_CHICK 92 92 -
GGVWQFSPGLC DRD4_MUSPF 93 93 -
DGVWSLNMTLC O42322 79 79 -
DGVWSLNMTVC Q5DJ16_DANRE 79 79 -

Motif 2 width=13
Element Seqn Id St Int Rpt
VPGRDPTVCCLED D4DR_RAT 172 66 -
VRGRDPAVCRLED D4DR_HUMAN 177 68 -
VPNRDPSLCQLED A5GXL4_PARMJ 159 68 -
VPNRDPSLCQLED B6UVA0_CHICK 171 68 -
ARGRDPAVCRLED DRD4_MUSPF 172 68 -
VPNRDHSECKLED O42322 158 68 -
VPNRDHSECKLED Q5DJ16_DANRE 158 68 -

Motif 3 width=16
Element Seqn Id St Int Rpt
FRGLRRWEAARHTKLH D4DR_RAT 211 26 -
FRGLQRWEVARRAKLH D4DR_HUMAN 216 26 -
FQGLKRWEEARKAKLR A5GXL4_PARMJ 198 26 -
FQGLKRWEEARKAKLR B6UVA0_CHICK 210 26 -
FRGLRRWEAARRTKLH DRD4_MUSPF 211 26 -
FRGLRNWEEARKAKLR O42322 197 26 -
FRGLRNWEEARKAKLR Q5DJ16_DANRE 197 26 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
GGVWLLSPRLC D4DR_RAT 95 95 -
GGVWLLSPRLC D4DR_MOUSE 95 95 -
GGVWLLSPRLC Q7TT80_MOUSE 95 95 -
GGAWLLSPRLC B0M0J7_HUMAN 98 98 -
GGAWLLSPRLC Q8NGM5_HUMAN 98 98 -
GGAWLLSPRLC D4DR_HUMAN 98 98 -
GGVWSLSTVLC A5GXL4_PARMJ 80 80 -
GGVWSLSTVLC B6UVA0_CHICK 92 92 -
GGVWQFSPGLC DRD4_MUSPF 93 93 -
DGVWSLNMTLC O42322 79 79 -
DGVWTLSTAVC Q4SUF1_TETNG 81 81 -
DGVWSLNMTVC Q5DJ16_DANRE 79 79 -
GGVWSLNVSVC Q5DJ14_DANRE 81 81 -

Motif 2 width=13
Element Seqn Id St Int Rpt
VPGRDPTVCCLED D4DR_RAT 172 66 -
VPGRDPAVCCLEN D4DR_MOUSE 172 66 -
VPGRDPAVCCLEN Q7TT80_MOUSE 172 66 -
VRGRDPAVCRLED B0M0J7_HUMAN 177 68 -
VRGRDPAVCRLED Q8NGM5_HUMAN 177 68 -
VRGRDPAVCRLED D4DR_HUMAN 177 68 -
VPNRDPSLCQLED A5GXL4_PARMJ 159 68 -
VPNRDPSLCQLED B6UVA0_CHICK 171 68 -
ARGRDPAVCRLED DRD4_MUSPF 172 68 -
VPNRDHSECKLED O42322 158 68 -
VPARDPGECKLEN Q4SUF1_TETNG 160 68 -
VPNRDHSECKLED Q5DJ16_DANRE 158 68 -
VPQRDPSECKLED Q5DJ14_DANRE 160 68 -

Motif 3 width=16
Element Seqn Id St Int Rpt
FRGLRRWEAARHTKLH D4DR_RAT 211 26 -
FRGLRRWEAARHTKLH D4DR_MOUSE 211 26 -
FRGLRRWEAARHTKLH Q7TT80_MOUSE 211 26 -
FRGLQRWEVARRAKLH B0M0J7_HUMAN 216 26 -
FRGLQRWEVARRAKLH Q8NGM5_HUMAN 216 26 -
FRGLQRWEVARRAKLH D4DR_HUMAN 216 26 -
FQGLKRWEEARKAKLR A5GXL4_PARMJ 198 26 -
FQGLKRWEEARKAKLR B6UVA0_CHICK 210 26 -
FRGLRRWEAARRTKLH DRD4_MUSPF 211 26 -
FRGLRNWEEARKAKLR O42322 197 26 -
FRGLRRWEEARKAKLR Q4SUF1_TETNG 199 26 -
FRGLRNWEEARKAKLR Q5DJ16_DANRE 197 26 -
FHGLRKWEETRKAKLR Q5DJ14_DANRE 199 26 -