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PR00565

Identifier
DOPAMINED1AR  [View Relations]  [View Alignment]  
Accession
PR00565
No. of Motifs
7
Creation Date
17-AUG-1996  (UPDATE 28-JUL-1999)
Title
Dopamine 1A receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00242 DOPAMINER
INTERPRO; IPR001413
GCRDB; GCR_0061; GCR_0062; GCR_0741; GCR_0915; GCR_0132
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.
 
D1 receptors are found in greatest abundance in the caudate-putamen,
nucleus accumbens and olfactory tubercle, with lower levels in the frontal
cortex, habenula, amygdala, hypothalamus and thalamus [7]. In the periphery,
binding sites are found in the kidney, heart, liver and parathyroid gland
[7]. The receptors stimulate adenylyl cyclase through Gs; they may also
be able to stimulate phosphoinositide metabolism [7]. 
 
DOPAMINED1AR is a 7-element fingerprint that provides a signature for the
D1A 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- and C-terminal regions, focusing on
those areas of the alignment that characterise the D1A receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motif 1
lies at the N-terminus; motifs 2 and 3 lie 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. Three partial matches were also found: A56849 is a
dopamine receptor-like protein D14 that fails to make significant matches
with motifs 2, 3, 5 and 6; G48909 is a dopamine receptor D1a fragment that
matches motifs 2 and 3; and DBDR_HUMAN is a dopamine D1B receptor, which
matches motifs 2 and 7.
 
An update on SPTR37_9f identified a true set of 6 sequences, and 6
partial matches.
Summary Information
   6 codes involving  7 elements
1 codes involving 6 elements
1 codes involving 5 elements
2 codes involving 4 elements
1 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
76666666
61101111
50101111
40202022
31001001
20100001
1234567
True Positives
DADR_DIDMA    DADR_HUMAN    DADR_PIG      DADR_RAT      
DADR_XENLA O77680
True Positive Partials
Codes involving 6 elements
Q98841
Codes involving 5 elements
Q98842
Codes involving 4 elements
O42315 O42316
Codes involving 3 elements
D1DR_FUGRU
Codes involving 2 elements
DBDR_HUMAN
Sequence Titles
DADR_DIDMA  D(1A) DOPAMINE RECEPTOR - DIDELPHIS MARSUPIALIS VIRGINIANA (NORTH AMERICAN OPOSSUM). 
DADR_HUMAN D(1A) DOPAMINE RECEPTOR - HOMO SAPIENS (HUMAN).
DADR_PIG D(1A) DOPAMINE RECEPTOR - SUS SCROFA (PIG).
DADR_RAT D(1A) DOPAMINE RECEPTOR - RATTUS NORVEGICUS (RAT).
DADR_XENLA D(1A) DOPAMINE RECEPTOR - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
O77680 D1 DOPAMINE RECEPTOR - MACACA MULATTA (RHESUS MACAQUE).

Q98841 DOPAMINE D1A1 RECEPTOR - ANGUILLA ANGUILLA (EUROPEAN FRESHWATER EEL).

Q98842 DOPAMINE D1A2 RECEPTOR - ANGUILLA ANGUILLA (EUROPEAN FRESHWATER EEL).

O42315 D1A3 DOPAMINE RECEPTOR - CYPRINUS CARPIO (COMMON CARP).
O42316 D1A4 DOPAMINE RECEPTOR - CYPRINUS CARPIO (COMMON CARP).

D1DR_FUGRU D(1)-LIKE DOPAMINE RECEPTOR - FUGU RUBRIPES (JAPANESE PUFFERFISH) (TAKIFUGU RUBRIPES).

DBDR_HUMAN D(1B) DOPAMINE RECEPTOR (D(5) DOPAMINE RECEPTOR) - HOMO SAPIENS (HUMAN).
Scan History
OWL28_1    1  100  NSINGLE    
SPTR37_9f 3 100 NSINGLE
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
MDEAGLPAERDFSFRIL DADR_RAT 8 8 -
MDGTGLVVERDFSVRIL DADR_HUMAN 9 9 -
MDGEGLLVERDSSFRIL A55886 8 8 -
MDGTGLVVERDFSFRIL SSU25681 9 9 -
MDEDVLLTERESSFRVL DADR_XENLA 8 8 -
MDRRGLVVERDFSFRIL DADR_DIDMA 8 8 -

Motif 2 width=12
Element Seqn Id St Int Rpt
RAAVHAKNCQNS DADR_XENLA 232 207 -
RAAVHAKNCQNT DADR_DIDMA 232 207 -
RAAVHAKNCQTT SSU25681 233 207 -
RAAVHAKNCQNT A55886 232 207 -
RAAVHAKNCQTT DADR_RAT 233 208 -
RAAVHAKNCQTT DADR_HUMAN 233 207 -

Motif 3 width=17
Element Seqn Id St Int Rpt
SGNRSSMDCQQPESNFK A55886 244 0 -
AGNGNPAECSQPESSFK SSU25681 245 0 -
TGNGKPVECSQPESSFK DADR_HUMAN 245 0 -
AGNGNPVECAQSESSFK DADR_RAT 245 0 -
TGNGANVECSQPESSFK DADR_DIDMA 244 0 -
TSNRNSLDCQQPESSLK DADR_XENLA 244 0 -

Motif 4 width=19
Element Seqn Id St Int Rpt
CPTTNNAIETVSINNNGAV DADR_RAT 351 89 -
CPATNNAIETVSINNNGAA DADR_HUMAN 351 89 -
CPMSGNAIETVSINNNGAV A55886 354 93 -
CPTSTNAIETVSINNNGAV SSU25681 351 89 -
CPTSNNIIETVSINNNGAV DADR_XENLA 354 93 -
CPTANNAIETVSINNNGAV DADR_DIDMA 354 93 -

Motif 5 width=22
Element Seqn Id St Int Rpt
FSSQHEPKGSSPKESNLVYLIP A55886 373 0 -
FSSHHEPRGSISKDCNLVYLIP SSU25681 371 1 -
FSSHHEPRGSISKECNLVYLIP DADR_HUMAN 371 1 -
FSSHHEPRGSISKDCNLVYLIP DADR_RAT 371 1 -
FSSHHEPRGSISKDCNLVYLIP DADR_DIDMA 373 0 -
YSCQQEPKGSIPNECNLVYLIP DADR_XENLA 374 1 -

Motif 6 width=17
Element Seqn Id St Int Rpt
SKPLEKTSPALSVILDY DADR_DIDMA 410 15 -
SKSLEKMSPAFSGILDY DADR_XENLA 415 19 -
SKTLEKMSPALSGMLDY A55886 414 19 -
ASPLEKLSPALSVILDY SSU25681 410 17 -
ARPLEKLSPALSVILDY DADR_HUMAN 410 17 -
AKPLEKLSPALSVILDY DADR_RAT 410 17 -

Motif 7 width=18
Element Seqn Id St Int Rpt
YDTDVSLEKIQPITQNGQ DADR_HUMAN 426 -1 -
YDTDVSLEKIQPITQNGQ SSU25681 426 -1 -
YDADVSLEKINPITQNGQ DADR_XENLA 431 -1 -
YEVDLSLEKINPITQNGQ DADR_DIDMA 426 -1 -
YDTDVSLEKIQPVTHSGQ DADR_RAT 426 -1 -
YEADVSLEKITPITQNGQ A55886 430 -1 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
MDGTGLVVERDFSVRIL DADR_HUMAN 9 9 -
MDGTGLVVERDFSVRIL O77680 9 9 -
MDGTGLVVERDFSFRIL DADR_PIG 9 9 -
MDEAGLPAERDFSFRIL DADR_RAT 8 8 -
MDRRGLVVERDFSFRIL DADR_DIDMA 8 8 -
MDEDVLLTERESSFRVL DADR_XENLA 8 8 -

Motif 2 width=12
Element Seqn Id St Int Rpt
RAAVHAKNCQTT DADR_HUMAN 233 207 -
RAAVHAKNCQTT O77680 233 207 -
RAAVHAKNCQTT DADR_PIG 233 207 -
RAAVHAKNCQTT DADR_RAT 233 208 -
RAAVHAKNCQNT DADR_DIDMA 232 207 -
RAAVHAKNCQNS DADR_XENLA 232 207 -

Motif 3 width=17
Element Seqn Id St Int Rpt
TGNGKPVECSQPESSFK DADR_HUMAN 245 0 -
TGNGKPVECSQPESSFK O77680 245 0 -
AGNGNPAECSQPESSFK DADR_PIG 245 0 -
AGNGNPVECAQSESSFK DADR_RAT 245 0 -
TGNGANVECSQPESSFK DADR_DIDMA 244 0 -
TSNRNSLDCQQPESSLK DADR_XENLA 244 0 -

Motif 4 width=19
Element Seqn Id St Int Rpt
CPATNNAIETVSINNNGAA DADR_HUMAN 351 89 -
CPATNNAIETVSINNNGAA O77680 351 89 -
CPTSTNAIETVSINNNGAV DADR_PIG 351 89 -
CPTTNNAIETVSINNNGAV DADR_RAT 351 89 -
CPTANNAIETVSINNNGAV DADR_DIDMA 354 93 -
CPTSNNIIETVSINNNGAV DADR_XENLA 354 93 -

Motif 5 width=22
Element Seqn Id St Int Rpt
FSSHHEPRGSISKECNLVYLIP DADR_HUMAN 371 1 -
FSSHHEPRGSISKECNLVYLIP O77680 371 1 -
FSSHHEPRGSISKDCNLVYLIP DADR_PIG 371 1 -
FSSHHEPRGSISKDCNLVYLIP DADR_RAT 371 1 -
FSSHHEPRGSISKDCNLVYLIP DADR_DIDMA 373 0 -
YSCQQEPKGSIPNECNLVYLIP DADR_XENLA 374 1 -

Motif 6 width=17
Element Seqn Id St Int Rpt
ARPLEKLSPALSVILDY DADR_HUMAN 410 17 -
ARPLEKLSPALSVILDY O77680 410 17 -
ASPLEKLSPALSVILDY DADR_PIG 410 17 -
AKPLEKLSPALSVILDY DADR_RAT 410 17 -
SKPLEKTSPALSVILDY DADR_DIDMA 410 15 -
SKSLEKMSPAFSGILDY DADR_XENLA 415 19 -

Motif 7 width=18
Element Seqn Id St Int Rpt
YDTDVSLEKIQPITQNGQ DADR_HUMAN 426 -1 -
YDTDVSLEKIQPITQNGQ O77680 426 -1 -
YDTDVSLEKIQPITQNGQ DADR_PIG 426 -1 -
YDTDVSLEKIQPVTHSGQ DADR_RAT 426 -1 -
YEVDLSLEKINPITQNGQ DADR_DIDMA 426 -1 -
YDADVSLEKINPITQNGQ DADR_XENLA 431 -1 -