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PR01784

Identifier
MCH2RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01784
No. of Motifs
9
Creation Date
25-SEP-2002
Title
Melanin-concentrating hormone 2 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01783 MCHRECEPTOR
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. CHAMBERS, J., AMES, R.S., BERGSMA, D., MUIR, A., FITZGERALD, L.R.,
HERVIEU, G., DYTKO, G.M., FOLEY, J.J., MARTIN, J., LIU, W.S., PARK, J.,
ELLIS, C., GANGULY, S., KONCHAR, S., CLUDERAY, J., LESLIE, R., WILSON, S.
AND SARAU, H.M.
Melanin-concentrating hormone is the cognate ligand for the orphan G
protein-coupled receptor SLC-1.
NATURE 400 261-265 (1999).
 
7. SAITO, Y., NOTHACKER, H.-P., WANG, Z., LIN, S.H.S., LESLIE, F. AND
CIVELLI, O.
Molecular characterization of the melanin-concentrating-hormone receptor.
NATURE 400 265-269 (1999).
 
8. SAITO, Y., NOTHACKER, H.-P. AND CIVELLI, O.
Melanin-concentrating hormone receptor: an orphan receptor fits the key.
TRENDS ENDOCRINOL.METAB. 11(8) 299-303 (2000).
 
9. HILL, J., DUCKWORTH, M., MURDOCK, P., RENNIE, G., SABIDO-DAVID, C., AMES,
R.S., SZEKERES, P., WILSON, S., BERGSMA, D.J., GLOGER, I.S., LEVY, D.S.,
CHAMBERS, J.K. AND MUIR, A.I.
Molecular cloning and functional characterization of MCH2, a novel human MCH
receptor.
J.BIOL.CHEM. 276(23) 20125-20129 (2001).

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].
 
Melanin-concentrating hormone (MCH) is a cyclic peptide originally
identified in teleost fish [6,7]. In fish, MCH is released from the
pituitary and causes lightening of skin pigment cells through pigment
aggregation [6,8]. In mammals, MCH is predominantly expressed in the
hypothalamus, and functions as a neurotransmitter in the control of a range
of functions [8]. A major role of MCH is thought to be in the regulation of
feeding: injection of MCH into rat brains stimulates feeding; expression of
MCH is upregulated in the hypothalamus of obese and fasting mice; and mice
lacking MCH are lean and eat less [6]. MCH and alpha melanocyte-stimulating
hormone (alpha-MSH) have antagonistic effects on a number of physiological
functions. Alpha-MSH darkens pigmentation in fish and reduces feeding in
mammals, whereas MCH increases feeding [6,8].
 
Two G protein-coupled receptors, MCH1 and MCH2, have recently been
identified as receptors for the hormone.
 
The expression profile of MCH2 is similar to that of MCH1, with highest
levels being found in the brain. However, expression of MCH2 is
significantly lower than MCH1 in the pituitary, hypothalamus, locus
coeruleus, medulla oblongata, and cerebellum [9]. Binding of MCH to the
receptor causes a pertussis toxin-insensitive increase in intracellular
calcium, suggesting coupling to Gq proteins [9].
 
MCH2RECEPTOR is a 9-element fingerprint that provides a signature for the
melanin-concentrating hormone 2 receptor. The fingerprint was derived from
an initial alignment of 5 sequences: the motifs were drawn from conserved
sections within N- and C-terminal and loop regions, focusing on those areas
of the alignment that characterise the MCH2 receptors but distinguish them
from the rest of the MCH receptor family - motifs 1 and 2 span the 
N-terminus; motif 3 encodes the first cytoplasmic loop; motif 4 lies in the
first external loop; motif 5 spans the second cytoplasmic loop, leading into
TM domain 4; motif 6 resides in the second external loop; motif 7 spans the
third cytoplasmic loop; motif 8 is located at the N-terminus of TM domain 7;
and motif 9 encodes the C-terminus. Two iterations on SPTR40_22f were 
required to reach convergence, at which point a true set comprising 6 
sequences was identified.
Summary Information
6 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
9666666666
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
Q8MIN7        Q8MIP5        Q8MJ88        Q8SQ54        
Q969V1 Q9BXA8
Sequence Titles
Q8MIN7      Melanin-concentrating hormone receptor subtype 2 MCH-2R - Mustela putorius (European polecat). 
Q8MIP5 Melanin-concentrating hormone receptor subtype 2 - Canis familiaris (Dog).
Q8MJ88 Melanin-concentrating hormone receptor subtype 2 - Macaca mulatta (Rhesus macaque).
Q8SQ54 GPRv17 - Macaca fascicularis (Crab eating macaque) (Cynomolgus monkey).
Q969V1 G protein-coupled receptor (Melanin-concentrating hormone 2 receptor) (Melanin-concentrating hormone receptor MCH-R2) (GPRv17) - Homo sapiens (Human).
Q9BXA8 G protein-coupled receptor MCH2 - Homo sapiens (Human).
Scan History
SPTR40_22f 2  200  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
HSSCWNTSAELSNKS Q8MJ88 5 5 -
HASCWNTSAELLNKS Q969V1 5 5 -
HASCWNTSAELLNKS Q9BXA8 5 5 -
HSSCWNTSAELLNKS Q8MIN7 5 5 -
HSSCWNTSAEPLNKS Q8MIP5 5 5 -

Motif 2 width=14
Element Seqn Id St Int Rpt
NKEFAYQTASVVDT Q8MJ88 21 1 -
NKEFAYQTASVVDT Q969V1 21 1 -
NKEFAYQTASVVDT Q9BXA8 21 1 -
NKESAYQTLRIVDT Q8MIN7 21 1 -
NKEFAYHTLSILDT Q8MIP5 21 1 -

Motif 3 width=11
Element Seqn Id St Int Rpt
VFTIIRSRKKT Q8MJ88 56 21 -
VFTIIRSRKKT Q969V1 56 21 -
VFTIIRSRKKT Q9BXA8 56 21 -
VFTIIRSRRKT Q8MIN7 56 21 -
VFTIIRSRKKT Q8MIP5 56 21 -

Motif 4 width=13
Element Seqn Id St Int Rpt
WARGGEWVFGGPL Q8MJ88 93 26 -
WARGGEWVFGGPL Q969V1 93 26 -
WARGGEWVFGGPL Q9BXA8 93 26 -
WARGGEWVFGGPL Q8MIN7 93 26 -
WARGGEWVFGGPL Q8MIP5 93 26 -

Motif 5 width=20
Element Seqn Id St Int Rpt
LVQPFRLTSWRTRYKTIRIN Q8MJ88 135 29 -
LVQPFRLTRWRTRYKTIRIN Q969V1 135 29 -
LVQPFRLTRWRTRYKTIRIN Q9BXA8 135 29 -
LVQPFRLTSWRTRYKTIRIN Q8MIN7 135 29 -
LVQPFRLTSWRTRYKTIRIN Q8MIP5 135 29 -

Motif 6 width=15
Element Seqn Id St Int Rpt
KFKDGVESCAFDLTS Q8MJ88 176 21 -
KFKDGVESCAFDLTS Q969V1 176 21 -
KFKDGVESCAFDLTS Q9BXA8 176 21 -
KFKDGVESCAFDLTS Q8MIN7 176 21 -
KFKDGVESCAFDLTS Q8MIP5 176 21 -

Motif 7 width=22
Element Seqn Id St Int Rpt
CYTWEMYQQNKDARCCNPSVPK Q8MJ88 222 31 -
CYTWEMYQQNKDARCCNPSVPK Q969V1 222 31 -
CYTWEMYQQNKDARCCNPSVPK Q9BXA8 222 31 -
CYTWEMYQQNKDARCYNPSVPK Q8MIN7 222 31 -
CYTWEMYQQNKDARCYNPSVPK Q8MIP5 222 31 -

Motif 8 width=14
Element Seqn Id St Int Rpt
YVGYYLSICLSYAS Q8MJ88 285 41 -
YVGYYLSICLSYAS Q969V1 285 41 -
YVGYYLSICLSYAS Q9BXA8 285 41 -
HVGYYLSICFSYAS Q8MIN7 285 41 -
HVGYYLSICFSYAS Q8MIP5 285 41 -

Motif 9 width=12
Element Seqn Id St Int Rpt
PQIQRRVTDKEI Q8MJ88 318 19 -
PQIQRRATEKEI Q969V1 318 19 -
PQIQRRATEKEI Q9BXA8 318 19 -
PQVQRRVTEREI Q8MIN7 318 19 -
PQVQRRVTEKST Q8MIP5 318 19 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
HSSCWNTSAELSNKS Q8MJ88 5 5 -
HASCWNTSAELLNKS Q969V1 5 5 -
HASCWNTSAELLNKS Q9BXA8 5 5 -
HSSCWNTSAELSNKS Q8SQ54 5 5 -
HSSCWNTSAELLNKS Q8MIN7 5 5 -
HSSCWNTSAEPLNKS Q8MIP5 5 5 -

Motif 2 width=14
Element Seqn Id St Int Rpt
NKEFAYQTASVVDT Q8MJ88 21 1 -
NKEFAYQTASVVDT Q969V1 21 1 -
NKEFAYQTASVVDT Q9BXA8 21 1 -
NKEFAYQTASAVDT Q8SQ54 21 1 -
NKESAYQTLRIVDT Q8MIN7 21 1 -
NKEFAYHTLSILDT Q8MIP5 21 1 -

Motif 3 width=11
Element Seqn Id St Int Rpt
VFTIIRSRKKT Q8MJ88 56 21 -
VFTIIRSRKKT Q969V1 56 21 -
VFTIIRSRKKT Q9BXA8 56 21 -
VFTIIRSRKKT Q8SQ54 56 21 -
VFTIIRSRRKT Q8MIN7 56 21 -
VFTIIRSRKKT Q8MIP5 56 21 -

Motif 4 width=13
Element Seqn Id St Int Rpt
WARGGEWVFGGPL Q8MJ88 93 26 -
WARGGEWVFGGPL Q969V1 93 26 -
WARGGEWVFGGPL Q9BXA8 93 26 -
WARGGEWVFGGPL Q8SQ54 93 26 -
WARGGEWVFGGPL Q8MIN7 93 26 -
WARGGEWVFGGPL Q8MIP5 93 26 -

Motif 5 width=20
Element Seqn Id St Int Rpt
LVQPFRLTSWRTRYKTIRIN Q8MJ88 135 29 -
LVQPFRLTRWRTRYKTIRIN Q969V1 135 29 -
LVQPFRLTRWRTRYKTIRIN Q9BXA8 135 29 -
LVQPFRLTSWRTRYKTIRIN Q8SQ54 135 29 -
LVQPFRLTSWRTRYKTIRIN Q8MIN7 135 29 -
LVQPFRLTSWRTRYKTIRIN Q8MIP5 135 29 -

Motif 6 width=15
Element Seqn Id St Int Rpt
KFKDGVESCAFDLTS Q8MJ88 176 21 -
KFKDGVESCAFDLTS Q969V1 176 21 -
KFKDGVESCAFDLTS Q9BXA8 176 21 -
KFKDGVESCAFDLTS Q8SQ54 176 21 -
KFKDGVESCAFDLTS Q8MIN7 176 21 -
KFKDGVESCAFDLTS Q8MIP5 176 21 -

Motif 7 width=22
Element Seqn Id St Int Rpt
CYTWEMYQQNKDARCCNPSVPK Q8MJ88 222 31 -
CYTWEMYQQNKDARCCNPSVPK Q969V1 222 31 -
CYTWEMYQQNKDARCCNPSVPK Q9BXA8 222 31 -
CYTWEMYQQNKDARCCNPSVPK Q8SQ54 222 31 -
CYTWEMYQQNKDARCYNPSVPK Q8MIN7 222 31 -
CYTWEMYQQNKDARCYNPSVPK Q8MIP5 222 31 -

Motif 8 width=14
Element Seqn Id St Int Rpt
YVGYYLSICLSYAS Q8MJ88 285 41 -
YVGYYLSICLSYAS Q969V1 285 41 -
YVGYYLSICLSYAS Q9BXA8 285 41 -
YVGYYLSICLSYAS Q8SQ54 285 41 -
HVGYYLSICFSYAS Q8MIN7 285 41 -
HVGYYLSICFSYAS Q8MIP5 285 41 -

Motif 9 width=12
Element Seqn Id St Int Rpt
PQIQRRVTDKEI Q8MJ88 318 19 -
PQIQRRATEKEI Q969V1 318 19 -
PQIQRRATEKEI Q9BXA8 318 19 -
PQIQRRVTDKEI Q8SQ54 318 19 -
PQVQRRVTEREI Q8MIN7 318 19 -
PQVQRRVTEKST Q8MIP5 318 19 -