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PR01061

Identifier
MELNOCORTN3R  [View Relations]  [View Alignment]  
Accession
PR01061
No. of Motifs
5
Creation Date
30-JAN-1999  (UPDATE 21-JUN-1999)
Title
Melanocortin 3 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00534 MCRFAMILY; PR00535 MELNOCORTINR
INTERPRO; IPR002122
GCRDB; GCR_0560; GCR_0655; GCR_0776
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. WATSON, S. AND ARKINSTALL, S.
Melanocortins.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.180-191.
 
7. GANTZ, I., KONDA, Y., TASHIRO, T., SHIMOTO, Y., MIWA, H., MUNZERT, G.,
WATSON, S.J., DELVALLE, J. AND YAMADA, T.
Molecular cloning of a novel melanocortin receptor.
J.BIOL.CHEM. 268 8246-8250 (1993). 
 
8. DESARNAUD, F., LABBE, O., EGGERICKX, D., VASSART, G. AND PARMENTIER, M.
Molecular cloning, functional expression and pharmacological 
characterization of a mouse melanocortin receptor gene.
BIOCHEM.J. 299 367-373 (1994). 
 
9. ROSELLI-REHFUSS, L., MOUNTJOY, K.G., ROBBINS, L.S., MORTRUD, M.T.,
LOW, M.J., TATRO, J.B., ENTWISTLE, M.L., SIMERLY, R.B. AND CONE, R.D.
Identification of a receptor for gamma melanotropin and other proopio-
melanocortin peptides in the hypothalamus and limbic system.
PROC.NATL.ACAD.SCI.U.S.A. 90 8856-8860 (1993). 

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]. 
 
Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) and
beta-endorphin are peptide products of pituitary pro-opiomelanocortin.
ACTH regulates synthesis and release of glucocorticoids and aldosterone
in the adrenal cortex; it also has a trophic action on these cells [6]. 
ACTH and beta-endorphin are synthesised and released in response to 
corticotrophin-releasing factor at times of stress (heat, cold, infections,
etc.) - their release leads to increased metabolism and analgesia res..
MSH has a trophic action on melanocytes, and regulates pigment production
in fish and amphibia [6]. The ACTH receptor is found in high levels in
the adrenal cortex - binding sites are present in lower levels in the
CNS. The MSH receptor is expressed in high levels in melanocytes, 
melanomas and their derived cell lines [6]. Receptors are found in low
levels in the CNS. MSH regulates temperature control in the septal region
of the brain and releases prolactin from the pituitary.
 
A further gene, which encodes a melanocortin receptor that is functionally
distinct from the ACTH and MSH receptors, has also been characterised [7-9].
The protein contains ~323 amino acids, with calculated molecular mass of 
35,800 Da, and potential N-linked glycosylation and phosphorylation sites
[8]. The melanocortin 3 receptor (MC3-R) is found in neurons of the arcuate 
nucleus known to express proopiomelanocortin and in a subset of the nuclei
to which these neurons send projections [9]. The MC3-R is 43% identical to 
the MSH receptor present in melanocytes and is strongly coupled to adenylyl
cyclase [9].
 
MELNOCORTN3R is a 5-element fingerprint that provides a signature for the
melanocortin 3 receptors. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved regions
spanning the full alignment length, focusing on those sections that 
characterise the melanocortin 3 receptors but distinguish them from the
rest of the melanocortin receptor family - motifs 1 and 2 lie at the
N-terminus; motif 3 lies in the first external loop; motif 4 spans the third
cytoplasmic loop; and motif 5 lies at the C-terminus. Two iterations on 
OWL27.1 were required to reach convergence, at which point a true set 
comprising 4 sequences was identified. A single partial match was also 
found, AB017137, a chicken melanocortin 3 receptor that fails to make
significant matches with motifs 1, 4 and 5.
 
An update on SPTR37_9f identified a true set of 3 sequences, and 1
partial match.
Summary Information
   3 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
533333
400000
300000
201100
12345
True Positives
MC3R_HUMAN    MC3R_MOUSE    MC3R_RAT      
True Positive Partials
Codes involving 2 elements
O93259
Sequence Titles
MC3R_HUMAN  Melanocortin receptor 3 (MC3-R) - Homo sapiens (Human). 
MC3R_MOUSE Melanocortin receptor 3 (MC3-R) - Mus musculus (Mouse).
MC3R_RAT Melanocortin receptor 3 (MC3-R) - Rattus norvegicus (Rat).

O93259 MELANOCORTIN 3-RECEPTOR - GALLUS GALLUS (CHICKEN).
Scan History
OWL31_1    2  100  NSINGLE    
SPTR37_9f 2 50 NSINGLE
Initial Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
NSSCCPSSSYPTLPNLSQHPAAP MC3R_RAT 2 2 -
NSSCCLSSVSPMLPNLSEHPAAP MC3R_MOUSE 2 2 -
NASCCLPSVQPTLPNGSEHLQAP MC3R_HUMAN 39 39 -

Motif 2 width=19
Element Seqn Id St Int Rpt
PSASNRSGSGFCEQVFIKP MC3R_RAT 24 -1 -
PPASNRSGSGFCEQVFIKP MC3R_MOUSE 24 -1 -
PFFSNQSSSAFCEQVFIKP MC3R_HUMAN 61 -1 -

Motif 3 width=16
Element Seqn Id St Int Rpt
NSDSLTLEDQFIQHMD MC3R_RAT 102 59 -
NSDSLTLEDQFIQHMD MC3R_MOUSE 102 59 -
HSDYLTFEDQFIQHMD MC3R_HUMAN 139 59 -

Motif 4 width=16
Element Seqn Id St Int Rpt
PPADGVAPQQHSCMKG MC3R_RAT 225 107 -
PPAGVVAPQQHSCMKG MC3R_MOUSE 225 107 -
PPADGVAPQQHSCMKG MC3R_HUMAN 262 107 -

Motif 5 width=10
Element Seqn Id St Int Rpt
ILCGCNGMNV MC3R_RAT 313 72 -
ILCGCNSMNL MC3R_MOUSE 313 72 -
ILCGCNGMNL MC3R_HUMAN 350 72 -
Final Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
NSSCCPSSSYPTLPNLSQHPAAP MC3R_RAT 2 2 -
NSSCCLSSVSPMLPNLSEHPAAP MC3R_MOUSE 2 2 -
NASCCLPSVQPTLPNGSEHLQAP MC3R_HUMAN 39 39 -

Motif 2 width=19
Element Seqn Id St Int Rpt
PSASNRSGSGFCEQVFIKP MC3R_RAT 24 -1 -
PPASNRSGSGFCEQVFIKP MC3R_MOUSE 24 -1 -
PFFSNQSSSAFCEQVFIKP MC3R_HUMAN 61 -1 -

Motif 3 width=16
Element Seqn Id St Int Rpt
NSDSLTLEDQFIQHMD MC3R_RAT 102 59 -
NSDSLTLEDQFIQHMD MC3R_MOUSE 102 59 -
HSDYLTFEDQFIQHMD MC3R_HUMAN 139 59 -

Motif 4 width=16
Element Seqn Id St Int Rpt
PPADGVAPQQHSCMKG MC3R_RAT 225 107 -
PPAGVVAPQQHSCMKG MC3R_MOUSE 225 107 -
PPADGVAPQQHSCMKG MC3R_HUMAN 262 107 -

Motif 5 width=10
Element Seqn Id St Int Rpt
ILCGCNGMNV MC3R_RAT 313 72 -
ILCGCNSMNL MC3R_MOUSE 313 72 -
ILCGCNGMNL MC3R_HUMAN 350 72 -