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PR01783

Identifier
MCHRECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01783
No. of Motifs
7
Creation Date
17-JUL-2002
Title
Melanin-concentrating hormone receptor family signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01784 MCH2RECEPTOR
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).

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 melanin-concentrating hormone.
 
MCHRECEPTOR is a 7-element fingerprint that provides a signature for the
melanin-concentrating hormone receptor family. The fingerprint was derived
from an initial alignment of 6 sequences: the motifs were drawn from
conserved sections within loop and TM regions, focusing on those areas of
the alignment that characterise the MCH receptors but distinguish them from
the rest of the rhodopsin-like superfamily - motif 1 lies in the N-terminal
portion of TM domain 1; motifs 2 and 3 span the N- and C-terminal portions
of TM domain 2, respectively; motif 4 is located in the first external loop;
motif 5 encodes the C-terminal portion of TM domain 4, leading into the
second external loop; motif 6 spans part of the second external loop,
leading into TM domain 5; and motif 7 encodes the C-terminal portion of TM
domain 6 and part of the third external loop. A single iteration on
SPTR40_20f was required to reach convergence, no further sequences being
identified beyond the starting set.
Summary Information
6 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
76666666
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
GPRO_HUMAN    GPRO_RAT      Q969V1        Q96S47        
Q9BV08 Q9BXA8
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).
Q969V1 G protein-coupled receptor (Melanin-concentrating hormone 2 receptor) (Melanin-concentrating hormone receptor MCH-R2) (GPRv17) - Homo sapiens (Human).
Q96S47 SOMATOSTATIN RECEPTOR-LIKE PROTEIN - Homo sapiens (Human).
Q9BV08 SIMILAR TO G PROTEIN-COUPLED RECEPTOR 24 (HYPOTHETICAL 46.0 KDA PROTEIN) - Homo sapiens (Human).
Q9BXA8 G protein-coupled receptor MCH2 - Homo sapiens (Human).
Scan History
SPTR40_20f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
YINIIMPSVFG GPRO_HUMAN 87 87 -
YINIIMPSVFG Q9BV08 107 107 -
YINIIMPSVFG Q96S47 107 107 -
YINIIMPSVFG GPRO_RAT 38 38 -
VDTVILPSMIG Q969V1 32 32 -
VDTVILPSMIG Q9BXA8 32 32 -

Motif 2 width=10
Element Seqn Id St Int Rpt
NVPDIFIINL GPRO_HUMAN 125 27 -
NVPDIFIINL Q9BV08 145 27 -
NVPDIFIINL Q96S47 145 27 -
NVPDIFIINL GPRO_RAT 76 27 -
TVPDIYICNL Q969V1 66 23 -
TVPDIYICNL Q9BXA8 66 23 -

Motif 3 width=12
Element Seqn Id St Int Rpt
FLLGMPFMIHQL GPRO_HUMAN 141 6 -
FLLGMPFMIHQL Q9BV08 161 6 -
FLLGMPFMIHQL Q96S47 161 6 -
FLLGMPFMIHQL GPRO_RAT 92 6 -
HIVGMPFLIHQW Q969V1 82 6 -
HIVGMPFLIHQW Q9BXA8 82 6 -

Motif 4 width=14
Element Seqn Id St Int Rpt
FGETMCTLITAMDA GPRO_HUMAN 160 7 -
FGETMCTLITAMDA Q9BV08 180 7 -
FGETMCTLITAMDA Q96S47 180 7 -
FGETMCTLITAMDA GPRO_RAT 111 7 -
FGGPLCTIITSLDT Q969V1 101 7 -
FGGPLCTIITSLDT Q9BXA8 101 7 -

Motif 5 width=14
Element Seqn Id St Int Rpt
PVWLYARLIPFPGG GPRO_HUMAN 226 52 -
PVWLYARLIPFPGG Q9BV08 246 52 -
PVWLYARLIPFPGG Q96S47 246 52 -
PVWLYARLIPFPGG GPRO_RAT 177 52 -
PVWVYSKVIKFKDG Q969V1 167 52 -
PVWVYSKVIKFKDG Q9BXA8 167 52 -

Motif 6 width=10
Element Seqn Id St Int Rpt
DLYWFTLYQF GPRO_HUMAN 253 13 -
DLYWFTLYQF Q9BV08 273 13 -
DLYWFTLYQF Q96S47 273 13 -
DLYWFTLYQF GPRO_RAT 204 13 -
DVLWYTLYLT Q969V1 193 12 -
DVLWYTLYLT Q9BXA8 193 12 -

Motif 7 width=14
Element Seqn Id St Int Rpt
VLQLTQLSISRPTL GPRO_HUMAN 323 60 -
VLQLTQLSISRPTL Q9BV08 343 60 -
VLQLTQLSISRPTL Q96S47 343 60 -
VLQLTQLSISRPTL GPRO_RAT 274 60 -
VIQLVNLQMEQPTL Q969V1 269 66 -
VIQLVNLQMEQPTL Q9BXA8 269 66 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
YINIIMPSVFG GPRO_HUMAN 87 87 -
YINIIMPSVFG Q9BV08 107 107 -
YINIIMPSVFG Q96S47 107 107 -
YINIIMPSVFG GPRO_RAT 38 38 -
VDTVILPSMIG Q969V1 32 32 -
VDTVILPSMIG Q9BXA8 32 32 -

Motif 2 width=10
Element Seqn Id St Int Rpt
NVPDIFIINL GPRO_HUMAN 125 27 -
NVPDIFIINL Q9BV08 145 27 -
NVPDIFIINL Q96S47 145 27 -
NVPDIFIINL GPRO_RAT 76 27 -
TVPDIYICNL Q969V1 66 23 -
TVPDIYICNL Q9BXA8 66 23 -

Motif 3 width=12
Element Seqn Id St Int Rpt
FLLGMPFMIHQL GPRO_HUMAN 141 6 -
FLLGMPFMIHQL Q9BV08 161 6 -
FLLGMPFMIHQL Q96S47 161 6 -
FLLGMPFMIHQL GPRO_RAT 92 6 -
HIVGMPFLIHQW Q969V1 82 6 -
HIVGMPFLIHQW Q9BXA8 82 6 -

Motif 4 width=14
Element Seqn Id St Int Rpt
FGETMCTLITAMDA GPRO_HUMAN 160 7 -
FGETMCTLITAMDA Q9BV08 180 7 -
FGETMCTLITAMDA Q96S47 180 7 -
FGETMCTLITAMDA GPRO_RAT 111 7 -
FGGPLCTIITSLDT Q969V1 101 7 -
FGGPLCTIITSLDT Q9BXA8 101 7 -

Motif 5 width=14
Element Seqn Id St Int Rpt
PVWLYARLIPFPGG GPRO_HUMAN 226 52 -
PVWLYARLIPFPGG Q9BV08 246 52 -
PVWLYARLIPFPGG Q96S47 246 52 -
PVWLYARLIPFPGG GPRO_RAT 177 52 -
PVWVYSKVIKFKDG Q969V1 167 52 -
PVWVYSKVIKFKDG Q9BXA8 167 52 -

Motif 6 width=10
Element Seqn Id St Int Rpt
DLYWFTLYQF GPRO_HUMAN 253 13 -
DLYWFTLYQF Q9BV08 273 13 -
DLYWFTLYQF Q96S47 273 13 -
DLYWFTLYQF GPRO_RAT 204 13 -
DVLWYTLYLT Q969V1 193 12 -
DVLWYTLYLT Q9BXA8 193 12 -

Motif 7 width=14
Element Seqn Id St Int Rpt
VLQLTQLSISRPTL GPRO_HUMAN 323 60 -
VLQLTQLSISRPTL Q9BV08 343 60 -
VLQLTQLSISRPTL Q96S47 343 60 -
VLQLTQLSISRPTL GPRO_RAT 274 60 -
VIQLVNLQMEQPTL Q969V1 269 66 -
VIQLVNLQMEQPTL Q9BXA8 269 66 -