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PR01064

Identifier
OREXINR  [View Relations]  [View Alignment]  
Accession
PR01064
No. of Motifs
10
Creation Date
14-FEB-1999  (UPDATE 07-JUN-1999)
Title
Orexin receptor signature 
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01521 OREXIN1R; PR01522 OREXIN2R
INTERPRO; IPR000204
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).

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. 
 
OREXINR is a 10-element fingerprint that provides a signature for orexin
receptors. The fingerprint was derived from an initial alignment of 4
sequences, focusing on those sections that characterise the orexin receptors
but distinguish them from the rest of the rhodopsin-like GPCR family - motifs
1 and 2 reside at the N-terminus; motif 3 spans the C-terminus of TM domain
2, leading into the first external loop; motif 4 lies in the second
cytoplasmic loop; motifs 5 and 6 span the second external loop; motifs 7 and
8 span the third cytoplasmic loop; motif 9 lies in the third external loop;
and motif 10 resides at the C-terminus. A single iteration on OWL31.1 was 
required to reach convergence, no further sequences being identified beyond
the starting set. A single partial match was found, an orexin receptor 
fragment that matches motifs 3 and 4.
 
An update on SPTR37_9f identified a true set of 2 sequences.
Summary Information
2 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 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
102222222222
90000000000
80000000000
70000000000
60000000000
50000000000
40000000000
30000000000
20000000000
12345678910
True Positives
O43613        O43614        
Sequence Titles
O43613      OREXIN RECEPTOR-1 - HOMO SAPIENS (HUMAN).     
O43614 OREXIN RECEPTOR-2 - HOMO SAPIENS (HUMAN).
Scan History
OWL31_1    1  100  NSINGLE    
SPTR37_9f 2 3 NSINGLE
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
EPSPVPPDYEDE AF041243 19 19 -
EPFHLPPDYEDE AF041244 19 19 -
EPFLNPTDYDDE AF041245 26 26 -
EPFLNPTDYDDE AF041246 26 26 -

Motif 2 width=17
Element Seqn Id St Int Rpt
FLRYLWRDYLYPKQYEW AF041243 31 0 -
FLRYLWRDYLYPKQYEW AF041244 31 0 -
FLRYLWREYLHPKEYEW AF041245 39 1 -
FLRYLWREYLHPKEYEW AF041246 39 1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
CLPASLLVDITESWLFG AF041243 99 51 -
CLPASLLVDITESWLFG AF041244 99 51 -
CLPATLVVDITETWFFG AF041245 107 51 -
CLPATLVVDITETWFFG AF041246 107 51 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PLLFKSTARRAR AF041243 151 35 -
PLLFKSTARRAR AF041244 151 35 -
PLMFKSTAKRAR AF041245 159 35 -
PLMFKSTAKRAR AF041246 159 35 -

Motif 5 width=17
Element Seqn Id St Int Rpt
PELANRTRLFSVCDERW AF041243 190 27 -
PELANRTRLFSVCDERW AF041244 190 27 -
PGLANKTTLFTVCDERW AF041245 198 27 -
PGLANKTTLFTVCDERW AF041246 198 27 -

Motif 6 width=19
Element Seqn Id St Int Rpt
WADDLYPKIYHSCFFIVTY AF041243 206 -1 -
WADELYPKIYHSCFFFVTY AF041244 206 -1 -
WGGEIYPKMYHICFFLVTY AF041245 214 -1 -
WGGEVYPKMYHICFFLVTY AF041246 214 -1 -

Motif 7 width=21
Element Seqn Id St Int Rpt
FRKLWGRQIPGTTSALVRNWK AF041243 239 14 -
FRKLWGPQIPGTTSALVRNWK AF041244 239 14 -
FRKLWCRQIPGTSSVVQRKWK AF041245 247 14 -
FRKLWCRQIPGTSSVVQRKWK AF041246 247 14 -

Motif 8 width=17
Element Seqn Id St Int Rpt
AFLAEVKQMRARRKTAK AF041243 282 22 -
AFLAEVKQMRARRKTAK AF041244 282 22 -
AVAAEIKQIRARRKTAR AF041245 288 20 -
AVAAEIKQIRARRKTAR AF041246 288 20 -

Motif 9 width=25
Element Seqn Id St Int Rpt
KRVFGMFRQASDREAVYACFTFSHW AF041243 321 22 -
KRVFGMFRQASDREAVYACFTFSHW AF041244 321 22 -
KRVFGMFAHTEDRETVYAWFTFSHW AF041245 327 22 -
KRVFGMFTHTEDRETVYAWFTFSHW AF041246 327 22 -

Motif 10 width=14
Element Seqn Id St Int Rpt
SKISEHVVLTSVTT AF041243 409 63 -
SKVSEHVVLTTVTT AF041244 400 54 -
SKLSEQVVLTSIST AF041245 418 66 -
SKLSEHVALTSIST AF041246 417 65 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
EPSPVPPDYEDE O43613 19 19 -
EPFLNPTDYDDE O43614 26 26 -

Motif 2 width=17
Element Seqn Id St Int Rpt
FLRYLWRDYLYPKQYEW O43613 31 0 -
FLRYLWREYLHPKEYEW O43614 39 1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
CLPASLLVDITESWLFG O43613 99 51 -
CLPATLVVDITETWFFG O43614 107 51 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PLLFKSTARRAR O43613 151 35 -
PLMFKSTAKRAR O43614 159 35 -

Motif 5 width=17
Element Seqn Id St Int Rpt
PELANRTRLFSVCDERW O43613 190 27 -
PGLANKTTLFTVCDERW O43614 198 27 -

Motif 6 width=19
Element Seqn Id St Int Rpt
WADDLYPKIYHSCFFIVTY O43613 206 -1 -
WGGEIYPKMYHICFFLVTY O43614 214 -1 -

Motif 7 width=21
Element Seqn Id St Int Rpt
FRKLWGRQIPGTTSALVRNWK O43613 239 14 -
FRKLWCRQIPGTSSVVQRKWK O43614 247 14 -

Motif 8 width=17
Element Seqn Id St Int Rpt
AFLAEVKQMRARRKTAK O43613 282 22 -
AVAAEIKQIRARRKTAR O43614 288 20 -

Motif 9 width=25
Element Seqn Id St Int Rpt
KRVFGMFRQASDREAVYACFTFSHW O43613 321 22 -
KRVFGMFAHTEDRETVYAWFTFSHW O43614 327 22 -

Motif 10 width=14
Element Seqn Id St Int Rpt
SKISEHVVLTSVTT O43613 409 63 -
SKLSEQVVLTSIST O43614 418 66 -