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PR01063

Identifier
MELNOCORTN5R  [View Relations]  [View Alignment]  
Accession
PR01063
No. of Motifs
5
Creation Date
30-JAN-1999  (UPDATE 07-JUN-1999)
Title
Melanocortin 5 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00534 MCRFAMILY; PR00535 MELNOCORTINR
INTERPRO; IPR000621
GCRDB; GCR_0793; GCR_0840; GCR_2058; GCR_0841; GCR_0939; GCR_2482

GCRDB; GCR_0952
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). 
 
10. GRIFFON, N., MIGNON, V., FACCHINETTI, P., DIAZ, J., SCHWARTZ, J.C.
AND SOKOLOFF, P.
Molecular cloning and characterization of the rat fifth melanocortin 
receptor.
BIOCHEM.BIOPHYS.RES.COMMUN. 200 1007-1014 (1994). 
 
11. GANTZ, I., SHIMOTO, Y., KONDA, Y., MIWA, H., DICKINSON, C.J.
AND YAMADA, T.
Molecular cloning, expression, and characterization of a fifth melanocortin
receptor.
BIOCHEM.BIOPHYS.RES.COMMUN. 200 1214-1220 (1994). 

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 [7-11].
The protein contains ~300 amino acids, with calculated molecular mass of 
~36 KDa, and potential N-linked glycosylation and phosphorylation sites
[8]. The melanocortin 5 receptor (MC5-R) mediates increase in cAMP 
accumulation with a characteristic pharmacology [10]. Very low expression
levels have been detected in brain, while high levels are found in adrenals,
stomach, lung and spleen [10]. In situ hybridisation studies have also shown
the MC5 receptor to be expressed in the three layers of the adrenal cortex,
predominantly in the aldosterone-producing zona glomerulosa cells [10]. 
Structure-activity studies have indicated that N- and C-terminal portions
of alpha-MSH appear to be key determinants in the activation of mouse 
MC5R, while the melanocortin core heptapeptide sequence is devoid of
pharmacological activity [11]. 
 
MELNOCORTN5R is a 5-element fingerprint that provides a signature for the
melanocortin 5 receptors. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved regions
spanning the full alignment length, focusing on those sections that
characterise the melanocortin 5 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 8 sequences was identified. Three partial matches were also
found, AB012211, MC4R_HUMAN and MC4R_RAT, all of which are melanocortin 4 
receptors match motifs 4 and 5.
 
An update on SPTR37_9f identified a true set of 6 sequences.
Summary Information
6 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
566666
400000
300000
200000
12345
True Positives
MC5R_BOVIN    MC5R_HUMAN    MC5R_MOUSE    MC5R_RAT      
MC5R_SHEEP O73671
Sequence Titles
MC5R_BOVIN  Melanocortin receptor 5 (MC5-R) - Bos taurus (Bovine). 
MC5R_HUMAN Melanocortin receptor 5 (MC5-R) (MC-2) - Homo sapiens (Human).
MC5R_MOUSE Melanocortin receptor 5 (MC5-R) - Mus musculus (Mouse).
MC5R_RAT Melanocortin receptor 5 (MC5-R) - Rattus norvegicus (Rat).
MC5R_SHEEP Melanocortin receptor 5 (MC5-R) - Ovis aries (Sheep).
O73671 MELANOCORTIN 5-RECEPTOR - GALLUS GALLUS (CHICKEN).
Scan History
OWL31_1    2  50   NSINGLE    
SPTR37_9f 2 8 NSINGLE
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
NSSFHLHFLDLGLNATEGN MC5R_SHEEP 2 2 -
NSSFHLHFLDLNLNATEGN MC5R_HUMAN 2 2 -
NSSSTLTVLNLTLNASEDG MC5R_MOUSE 2 2 -
NSSSHLTLLDLTLNASEDN MC5R_RAT 2 2 -

Motif 2 width=19
Element Seqn Id St Int Rpt
GLSVRNASSPCEDMGIAVE MC5R_SHEEP 23 2 -
GPNVKNKSSPCEDMGIAVE MC5R_HUMAN 23 2 -
GSNVKNKSLACEEMGIAVE MC5R_MOUSE 23 2 -
GQNVNNKSSACEDMGIAVE MC5R_RAT 23 2 -

Motif 3 width=19
Element Seqn Id St Int Rpt
TIYLLTNKHLVMADASVRH MC5R_SHEEP 95 53 -
TIYLLNNKHLVIADAFVRH MC5R_HUMAN 95 53 -
TIYLLNNKHLVIADTFVRH MC5R_MOUSE 95 53 -
TIYLINNKHVVIADTFVRH MC5R_RAT 95 53 -

Motif 4 width=17
Element Seqn Id St Int Rpt
ALPGHSSVRQRTGVKGA MC5R_SHEEP 221 107 -
ALPGASSARQRTSMQGA MC5R_HUMAN 221 107 -
ASPRYNSVRQRTSMKGA MC5R_MOUSE 221 107 -
ASPRYNSVRQRASMKGA MC5R_RAT 221 107 -

Motif 5 width=15
Element Seqn Id St Int Rpt
EIVCFQGFRTPCRFP MC5R_SHEEP 308 70 -
EIICCRGFRIACSFP MC5R_HUMAN 308 70 -
EIVCCHGFRRPCRLL MC5R_MOUSE 308 70 -
EIICCHGFRRTCTLL MC5R_RAT 308 70 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
NSSFHLHFLDLGLNATEGN MC5R_SHEEP 2 2 -
NSSFHLHFLDLNLNATEGN MC5R_HUMAN 2 2 -
NSSSTLTVLNLTLNASEDG MC5R_MOUSE 2 2 -
NSSSHLTLLDLTLNASEDN MC5R_RAT 2 2 -
NSSFHLHFLDLGLNTTDGN MC5R_BOVIN 2 2 -
NTSSQLYVSELNLSAFGSN O73671 2 2 -

Motif 2 width=19
Element Seqn Id St Int Rpt
GLSVRNASSPCEDMGIAVE MC5R_SHEEP 23 2 -
GPNVKNKSSPCEDMGIAVE MC5R_HUMAN 23 2 -
GSNVKNKSLACEEMGIAVE MC5R_MOUSE 23 2 -
GQNVNNKSSACEDMGIAVE MC5R_RAT 23 2 -
GLSVQNASSLCEDMGIAVE MC5R_BOVIN 23 2 -
VPTVKSKSSPCEQVVIAAE O73671 23 2 -

Motif 3 width=19
Element Seqn Id St Int Rpt
TIYLLTNKHLVMADASVRH MC5R_SHEEP 95 53 -
TIYLLNNKHLVIADAFVRH MC5R_HUMAN 95 53 -
TIYLLNNKHLVIADTFVRH MC5R_MOUSE 95 53 -
TIYLINNKHVVIADTFVRH MC5R_RAT 95 53 -
TIYLLTNKHLVMADASVRH MC5R_BOVIN 95 53 -
TIYLINNRHIIMEDAFVRH O73671 95 53 -

Motif 4 width=17
Element Seqn Id St Int Rpt
ALPGHSSVRQRTGVKGA MC5R_SHEEP 221 107 -
ALPGASSARQRTSMQGA MC5R_HUMAN 221 107 -
ASPRYNSVRQRTSMKGA MC5R_MOUSE 221 107 -
ASPRYNSVRQRASMKGA MC5R_RAT 221 107 -
TLPGHSSVRQRTGVKGA MC5R_BOVIN 221 107 -
ALPGYNSVHQRTSMKGA O73671 221 107 -

Motif 5 width=15
Element Seqn Id St Int Rpt
EIVCFQGFRTPCRFP MC5R_SHEEP 308 70 -
EIICCRGFRIACSFP MC5R_HUMAN 308 70 -
EIVCCHGFRRPCRLL MC5R_MOUSE 308 70 -
EIICCHGFRRTCTLL MC5R_RAT 308 70 -
EIVCFQSFRTPCRFP MC5R_BOVIN 308 70 -
EIICCYSVRMVCGLS O73671 308 70 -