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PR01507

Identifier
MCH1RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01507
No. of Motifs
9
Creation Date
19-JUN-2001
Title
Melanin-concentrating hormone 1 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
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. HAWES, B.E., KIL, E., GREEN, B., O'NEILL, K., FRIED, S. AND GRAZIANO, M.P.
The melanin-concentrating hormone receptor couples to multiple G proteins to
activate diverse intracellular signaling pathways.
ENDOCRINOLOGY 141(12) 4524-4532 (2000).

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 [1,2]. In fish, MCH is released from the
pituitary and causes lightening of skin pigment cells through pigment
aggregation [1,3]. In mammals, MCH is predominantly expressed in the
hypothalamus, and functions as a neurotransmitter in the control of a range
of functions [3]. 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 [1]. 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 [1,3].
 
An orphan GPCR, previously known as SLC-1, has been identified as a
receptor for MCH [1,2]. Expression of the receptor has been found at highest
levels in the brain, with moderate levels in the eye and skeletal muscle,
and lower levels in the tongue and pituitary [2]. In the brain, the receptor
is expressed extensively in the hippocampus, olfactory regions and medial
nucleus accumbens, a distribution that corresponds to connections between
MCH-containing neurons and areas of the brain involved in taste and
olfaction [2,3]. This supports a role for the MCH receptor in olfactory
learning and reinforcement mechanisms. The receptor is also found in parts
of the hypothalamus, such as the ventromedial nucleus, that are known to
regulate feeding and metabolism [2,3]. The MCH receptor is expressed at
moderate levels in the substantia nigra, ventral tegmental area and
amygdala, suggesting that MCH may modulate the dopaminergic system [2].
Expression has also been found in the locus coeruleus, indicating a possible
role in the control of noradrenaline responses, including vigilance,
attention, memory and sleep [2]. Binding of MCH to the receptor results in
inhibition of forskolin-stimulated cyclic AMP accumulation in a pertussis
toxin sensitive manner, release of intracellular calcium in a partially
pertussis toxin sensitive manner and activation of MAP kinase in a partially
protein kinase C dependent manner [4]. This indicates that the MCH receptor
is capable of coupling to G proteins of the Gi, Go and Gq classes [4].
 
MCH1RECEPTOR is a 9-element fingerprint that provides a signature for the
melanin-concentrating hormone 1 receptors. The fingerprint was derived
from an initial alignment of 2 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 MCH 1 receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motif 1
lies at the N-terminus; motifs 2-7 encode each of the cytoplasmic and
external loops; and motifs 8 and 9 reside at the 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  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
9222222222
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
GPRO_HUMAN    GPRO_RAT      
Sequence Titles
GPRO_HUMAN  Probable G protein-coupled receptor GPR24 (SLC-1) - Homo sapiens (Human). 
GPRO_RAT Probable G protein-coupled receptor GPR24 (SLC-1) - Rattus norvegicus (Rat).
Scan History
SPTR39_15f 1  35   NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
PGSPPRTGSISYINI GPRO_HUMAN 76 76 -
PGSPPRTGSVSYINI GPRO_RAT 27 27 -

Motif 2 width=15
Element Seqn Id St Int Rpt
FAVVKKSKLHWCNNV GPRO_HUMAN 112 21 -
FAVVKKSKLHWCSNV GPRO_RAT 63 21 -

Motif 3 width=11
Element Seqn Id St Int Rpt
QLMGNGVWHFG GPRO_HUMAN 151 24 -
QLMGNGVWHFG GPRO_RAT 102 24 -

Motif 4 width=23
Element Seqn Id St Int Rpt
TVHPISSTKFRKPSVATLVICLL GPRO_HUMAN 194 32 -
TVHPISSTKFRKPSMATLVICLL GPRO_RAT 145 32 -

Motif 5 width=21
Element Seqn Id St Int Rpt
PFPGGAVGCGIRLPNPDTDLY GPRO_HUMAN 235 18 -
PFPGGAVGCGIRLPNPDTDLY GPRO_RAT 186 18 -

Motif 6 width=24
Element Seqn Id St Int Rpt
VRILQRMTSSVAPASQRSIRLRTK GPRO_HUMAN 278 22 -
VKILQRMTSSVAPASQRSIRLRTK GPRO_RAT 229 22 -

Motif 7 width=20
Element Seqn Id St Int Rpt
SISRPTLTFVYLYNAAISLG GPRO_HUMAN 330 28 -
SISRPTLTFVYLYNAAISLG GPRO_RAT 281 28 -

Motif 8 width=20
Element Seqn Id St Int Rpt
CETFRKRLVLSVKPAAQGQL GPRO_HUMAN 364 14 -
CETFRKRLVLSVKPAAQGQL GPRO_RAT 315 14 -

Motif 9 width=20
Element Seqn Id St Int Rpt
LRAVSNAQTADEERTESKGT GPRO_HUMAN 383 -1 -
LRTVSNAQTADEERTESKGT GPRO_RAT 334 -1 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
PGSPPRTGSISYINI GPRO_HUMAN 76 76 -
PGSPPRTGSVSYINI GPRO_RAT 27 27 -

Motif 2 width=15
Element Seqn Id St Int Rpt
FAVVKKSKLHWCNNV GPRO_HUMAN 112 21 -
FAVVKKSKLHWCSNV GPRO_RAT 63 21 -

Motif 3 width=11
Element Seqn Id St Int Rpt
QLMGNGVWHFG GPRO_HUMAN 151 24 -
QLMGNGVWHFG GPRO_RAT 102 24 -

Motif 4 width=23
Element Seqn Id St Int Rpt
TVHPISSTKFRKPSVATLVICLL GPRO_HUMAN 194 32 -
TVHPISSTKFRKPSMATLVICLL GPRO_RAT 145 32 -

Motif 5 width=21
Element Seqn Id St Int Rpt
PFPGGAVGCGIRLPNPDTDLY GPRO_HUMAN 235 18 -
PFPGGAVGCGIRLPNPDTDLY GPRO_RAT 186 18 -

Motif 6 width=24
Element Seqn Id St Int Rpt
VRILQRMTSSVAPASQRSIRLRTK GPRO_HUMAN 278 22 -
VKILQRMTSSVAPASQRSIRLRTK GPRO_RAT 229 22 -

Motif 7 width=20
Element Seqn Id St Int Rpt
SISRPTLTFVYLYNAAISLG GPRO_HUMAN 330 28 -
SISRPTLTFVYLYNAAISLG GPRO_RAT 281 28 -

Motif 8 width=20
Element Seqn Id St Int Rpt
CETFRKRLVLSVKPAAQGQL GPRO_HUMAN 364 14 -
CETFRKRLVLSVKPAAQGQL GPRO_RAT 315 14 -

Motif 9 width=20
Element Seqn Id St Int Rpt
LRAVSNAQTADEERTESKGT GPRO_HUMAN 383 -1 -
LRTVSNAQTADEERTESKGT GPRO_RAT 334 -1 -