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PR01521

Identifier
OREXIN1R  [View Relations]  [View Alignment]  
Accession
PR01521
No. of Motifs
4
Creation Date
18-JUN-2001
Title
Orexin receptor type 1 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01064 OREXINR
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. SAKURAI, T., AMEMIYA, A., ISHII, M., MATSUZAKI, I., CHEMELLI, R.M.,
TANAKA, H., WILLIAMS, S.C., RICHARDSON, J.A., KOZLOWSKI, G.P., WILSON, S.,
ARCH, J.R., BUCKINGHAM, R.E., HAYNES, A.C., CARR, S.A., ANNAN, R.S.,
MCNULTY, D.E., LIU, W.S., TERRETT, J.A., ELSHOURBAGY, N.A., BERGSMA, D.J.
AND YANAGISAWA, M.
Orexins and orexin receptors: a family of hypothalamic neuropeptides and 
G protein-coupled receptors that regulate feeding behavior.
CELL 92(4) 573-85 (1998).
 
7. WOLF, G.
Orexins: a newly discovered family of hypothalamic regulators of food
intake.
NUTR.REV. 56(6) 172-3 (1998).
 
8. SMART. D., JERMAN, J.C., BROUGH, S.J., RUSHTON, S.L., MURDOCK, P.R.,
JEWITT, F., ELSHOURBAGY, N.A., ELLIS, C.E., MIDDLEMISS, D.N. AND BROWN, F.
Characterization of recombinant human orexin receptor pharmacology in a
chinese hamster ovary cell-line using FLIPR.
BR.J.PHARMACOL. 128 1-3 (1999).

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]. 
 
The hypothalamus plays a central role in the integrated control of feeding
and energy homeostasis [6]. A new family of neuropeptides, orexins, have
been identified that bind and activate two closely related (previously) 
orphan GPCRs [6,7]. Orexins stimulate appetite and food consumption [7].
Their genes are expressed bilaterally and symmetrically in the lateral
hypothalamus, which has been shown to be the "feeding centre". By contrast,
the "satiety centre" is expressed in the ventromedial hypothalamus and is
dominated by the leptin-regulated neuropeptide network.
 
Both orexin receptors exhibit a similar pharmacology - the 2 orexin
peptides, orexin-A and orexin-B, bind to both receptors and, in each case,
agonist binding results in an increase in intracellular calcium levels. 
However, orexin-B shows a 10-fold selectivity for orexin receptor
type 2, whilst orexin-A is equipotent at both receptors [8].
 
OREXIN1R is a 4-element fingerprint that provides a signature for type 1
orexin receptors. The fingerprint was derived from an initial alignment of 2
sequences: the motifs were drawn from conserved regions spanning the
C-terminal half of the alignment, focusing on those sections that
characterise the type 1 receptors but distinguish them from the rest of
the orexin receptor family - motif 1 spans the third cytoplasmic loop; and
motifs 2-4 reside at the cytoplasmic C-terminus. A single iteration on
SPTR39_15f was required to reach convergence, no further sequences being
identified beyond the starting set.
Summary Information
2 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
42222
30000
20000
1234
True Positives
O43613        OX1R_RAT      
Sequence Titles
O43613      OREXIN RECEPTOR-1 - HOMO SAPIENS (HUMAN).     
OX1R_RAT Orexin receptor type 1 (Ox1r) (Hypocretin receptor type 1) - Rattus norvegicus (Rat).
Scan History
SPTR39_15f 1  250  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
ALVRNWKRPSDQL O43613 253 253 -
ALVRNWKRPSEQL OX1R_RAT 253 253 -

Motif 2 width=12
Element Seqn Id St Int Rpt
SSASHKSLSLQS O43613 393 127 -
SSARHKSLSLQS OX1R_RAT 384 118 -

Motif 3 width=10
Element Seqn Id St Int Rpt
RCSISKISEH O43613 405 0 -
RCSVSKVSEH OX1R_RAT 396 0 -

Motif 4 width=11
Element Seqn Id St Int Rpt
VVLTSVTTVLP O43613 415 0 -
VVLTTVTTVLS OX1R_RAT 406 0 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
ALVRNWKRPSDQL O43613 253 253 -
ALVRNWKRPSEQL OX1R_RAT 253 253 -

Motif 2 width=12
Element Seqn Id St Int Rpt
SSASHKSLSLQS O43613 393 127 -
SSARHKSLSLQS OX1R_RAT 384 118 -

Motif 3 width=10
Element Seqn Id St Int Rpt
RCSISKISEH O43613 405 0 -
RCSVSKVSEH OX1R_RAT 396 0 -

Motif 4 width=11
Element Seqn Id St Int Rpt
VVLTSVTTVLP O43613 415 0 -
VVLTTVTTVLS OX1R_RAT 406 0 -