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PR00567

Identifier
DOPAMINED2R  [View Relations]  [View Alignment]  
Accession
PR00567
No. of Motifs
6
Creation Date
17-AUG-1996  (UPDATE 07-JUN-1999)
Title
Dopamine D2 receptor signature 
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00242 DOPAMINER
INTERPRO; IPR001922
GCRDB; GCR_0063; GCR_0065; GCR_0066; GCR_0307; GCR_0310; GCR_0095

GCRDB; GCR_0133
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.
 
D2 receptors have a similar pharmacological profile to D3 and D4 receptors.
They are present in high levels in the principal dopamine projection areas
(including the caudate-putamen, nucleus accumbens and olfactory tubercle);
they are found in cell bodies of dopaminergic neurons in the substantia
nigra and ventral tegmental area; and, in the periphery, they are found in
the pituitary, heart and blood vessels [7].
 
DOPAMINED2R is a 6-element fingerprint that provides a signature for the
D2 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 D2 receptors but distinguish them from the
rest of the rhodopsin-like superfamily - motif 1 lies at the N-terminus;
motifs 2-5 span the third cytoplasmic loop; and motif 6 spans the third
external loop. 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, D2D2_XENLA, a D2 receptor fragment
lacking the first motif.
 
An update on SPTR37_9f identified a true set of 6 sequences.
Summary Information
6 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
6666666
5000000
4000000
3000000
2000000
123456
True Positives
D2D1_XENLA    D2DR_BOVIN    D2DR_CERAE    D2DR_HUMAN    
D2DR_MOUSE O73810
Sequence Titles
D2D1_XENLA  D(2) DOPAMINE RECEPTOR 1 - XENOPUS LAEVIS (AFRICAN CLAWED FROG). 
D2DR_BOVIN D(2) DOPAMINE RECEPTOR - BOS TAURUS (BOVINE).
D2DR_CERAE D(2) DOPAMINE RECEPTOR - CERCOPITHECUS AETHIOPS (GREEN MONKEY) (GRIVET).
D2DR_HUMAN D(2) DOPAMINE RECEPTOR - HOMO SAPIENS (HUMAN).
D2DR_MOUSE D(2) DOPAMINE RECEPTOR - MUS MUSCULUS (MOUSE), AND RATTUS NORVEGICUS (RAT).
O73810 D2 DOPAMINE RECEPTOR - MELEAGRIS GALLOPAVO (COMMON TURKEY).
Scan History
OWL28_1    1  50   NSINGLE    
SPTR37_9f 2 7 NSINGLE
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
DPLNLSWYDDDL D2DR_RAT 2 2 -
DPLNLSWYDDDL CAU18547 2 2 -
DPLNLSWYDDDL RND2DOPR 2 2 -
DPLNLSWYDDDL D2DR_HUMAN 2 2 -
DPLNLSWYDDDP D2DR_BOVIN 2 2 -
DPQNLSMYNDDI D2D1_XENLA 2 2 -

Motif 2 width=21
Element Seqn Id St Int Rpt
CTHPEDMKLCTVIMKSNGSFP RND2DOPR 244 230 -
CTHPEDMKLCTVIMKSNGSFP D2DR_HUMAN 244 230 -
CTHPEDMKLCTVIMKSNGSFP D2DR_BOVIN 244 230 -
CTHPEDVKLCSVFVKSNGSFP D2D1_XENLA 235 221 -
CTHPEDMKLCTVIMKSNGSFP D2DR_RAT 244 230 -
CTHPEDMKLCTVIMKSNGSFP CAU18547 244 230 -

Motif 3 width=15
Element Seqn Id St Int Rpt
EMEMLSSTSPPERTR D2DR_RAT 280 15 -
EMEMLSSTSPPERTR RND2DOPR 280 15 -
EMEMLSSTSPPERTR CAU18547 280 15 -
EMEMMSSTSPPEKTK D2D1_XENLA 275 19 -
EMEMLSSTSPPERTR D2DR_BOVIN 280 15 -
EMEMLSSTSPPERTR D2DR_HUMAN 280 15 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LHSNPDSPAKPEKNGHAK RND2DOPR 315 20 -
LHSTPDSPAKPEKNGHAK D2DR_HUMAN 315 20 -
LHSTPDSPAKPEKNGHAK D2DR_BOVIN 315 20 -
LTSPVESPYKAEKNGHPK D2D1_XENLA 314 24 -
LHSNPDSPAKPEKNGHAK D2DR_RAT 315 20 -
LHSTPDSPAKPEKNGHAK CAU18547 315 20 -

Motif 5 width=15
Element Seqn Id St Int Rpt
PKIAKIFEIQTMPNG D2DR_HUMAN 335 2 -
PRIAKFFEIQTMPNG RND2DOPR 336 3 -
PKIAKIFEIQTMPNG CAU18547 335 2 -
PKIAKIFEIQSMPNG D2DR_BOVIN 336 3 -
TKPAKVFEIQSMPNG D2D1_XENLA 334 2 -
PRIAKFFEIQTMPNG D2DR_RAT 336 3 -

Motif 6 width=15
Element Seqn Id St Int Rpt
NIHCDCNIPPVLYSA D2DR_HUMAN 396 46 -
NIHCDCNIPPVLYSA CAU18547 396 46 -
NIHCDCNIPPVLYSA D2DR_RAT 397 46 -
NIHCDCNIPPVLYSA D2DR_BOVIN 397 46 -
NMHCNCNIPQALYSA D2D1_XENLA 395 46 -
NIHCDCNIPPVLYSA RND2DOPR 397 46 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
DPLNLSWYDDDL D2DR_CERAE 2 2 -
DPLNLSWYDDDL D2DR_HUMAN 2 2 -
DPLNLSWYDDDP D2DR_BOVIN 2 2 -
DPLNLSWYDDDL D2DR_MOUSE 2 2 -
DPLNLSWYNTGD O73810 2 2 -
DPQNLSMYNDDI D2D1_XENLA 2 2 -

Motif 2 width=21
Element Seqn Id St Int Rpt
CTHPEDMKLCTVIMKSNGSFP D2DR_CERAE 244 230 -
CTHPEDMKLCTVIMKSNGSFP D2DR_HUMAN 244 230 -
CTHPEDMKLCTVIMKSNGSFP D2DR_BOVIN 244 230 -
CTHPEDMKLCTVIMKSNGSFP D2DR_MOUSE 244 230 -
CTHPENVKLGTVIVKSNGSFQ O73810 240 226 -
CTHPEDVKLCSVFVKSNGSFP D2D1_XENLA 235 221 -

Motif 3 width=15
Element Seqn Id St Int Rpt
EMEMLSSTSPPERTR D2DR_CERAE 280 15 -
EMEMLSSTSPPERTR D2DR_HUMAN 280 15 -
EMEMLSSTSPPERTR D2DR_BOVIN 280 15 -
EMEMLSSTSPPERTR D2DR_MOUSE 280 15 -
EMEMMSSTSPPERTI O73810 275 14 -
EMEMMSSTSPPEKTK D2D1_XENLA 275 19 -

Motif 4 width=18
Element Seqn Id St Int Rpt
LHSTPDSPAKPEKNGHAK D2DR_CERAE 315 20 -
LHSTPDSPAKPEKNGHAK D2DR_HUMAN 315 20 -
LHSTPDSPAKPEKNGHAK D2DR_BOVIN 315 20 -
LHSNPDSPAKPEKNGHAK D2DR_MOUSE 315 20 -
SRSTLDSPGKVEKNGHAK O73810 307 17 -
LTSPVESPYKAEKNGHPK D2D1_XENLA 314 24 -

Motif 5 width=15
Element Seqn Id St Int Rpt
PKIAKIFEIQTMPNG D2DR_CERAE 335 2 -
PKIAKIFEIQTMPNG D2DR_HUMAN 335 2 -
PKIAKIFEIQSMPNG D2DR_BOVIN 336 3 -
PRIAKFFEIQTMPNG D2DR_MOUSE 336 3 -
LHTAKVFEIQSMPNG O73810 327 2 -
TKPAKVFEIQSMPNG D2D1_XENLA 334 2 -

Motif 6 width=15
Element Seqn Id St Int Rpt
NIHCDCNIPPVLYSA D2DR_CERAE 396 46 -
NIHCDCNIPPVLYSA D2DR_HUMAN 396 46 -
NIHCDCNIPPVLYSA D2DR_BOVIN 397 46 -
NIHCDCNIPPVLYSA D2DR_MOUSE 397 46 -
NMHCDCNIPPAMYSA O73810 389 47 -
NMHCNCNIPQALYSA D2D1_XENLA 395 46 -