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PR00535

Identifier
MELNOCORTINR  [View Relations]  [View Alignment]  
Accession
PR00535
No. of Motifs
6
Creation Date
20-MAY-1996  (UPDATE 07-JUN-1999)
Title
Melanocortin receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00534 MCRFAMILY; PR01061 MELNOCORTN3R; PR01062 MELNOCORTN4R
PRINTS; PR01063 MELNOCORTN5R
INTERPRO; IPR001908
GCRDB; GCR_0840; GCR_0841; GCR_0793
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.

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.
 
MELNOCORTINR is a 6-element fingerprint that provides a signature for the
melanocortin receptors. The fingerprint was derived from an initial
alignment of 5 sequences: the motifs were drawn from conserved sections
within either loop or TM regions, focusing on those areas of the alignment
that characterise the melanocortin receptors but distinguish them from the
rest of the melanocortin receptor family - motif 1 spans the second
external loop leading into TM domain 5; motif 2 was drawn from the central
portion of TM domain 5; motif 3 forms part of the third cytoplasmic loop;
motifs 4 and 5 span the third external loop; and motif 6 resides in the
C-terminal region following TM domain 7. Two iterations on OWL27.1 were
required to reach convergence, at which point a true set comprising 11
sequences was identified. Two partial matches were also found, a
melanocortin receptor fragment (B57055) and a sequence designated a
melanocortin type 1 receptor (CHKM1R) that bears closer sequence
similarity to the MSH receptor family.
 
An update on SPTR37_9f identified a true set of 13 sequences, and 1
partial match.
Summary Information
  13 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
6131313131313
5000000
4000000
3000000
2000110
123456
True Positives
MC3R_HUMAN    MC3R_MOUSE    MC3R_RAT      MC4R_HUMAN    
MC4R_RAT MC5R_BOVIN MC5R_HUMAN MC5R_MOUSE
MC5R_RAT MC5R_SHEEP O73667 O73671
O93259
True Positive Partials
Codes involving 2 elements
MSHR_CHICK
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).
MC4R_HUMAN Melanocortin receptor 4 (MC4-R) - Homo sapiens (Human).
MC4R_RAT Melanocortin receptor 4 (MC4-R) - Rattus norvegicus (Rat).
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).
O73667 MELANOCORTIN 4-RECEPTOR - GALLUS GALLUS (CHICKEN).
O73671 MELANOCORTIN 5-RECEPTOR - GALLUS GALLUS (CHICKEN).
O93259 MELANOCORTIN 3-RECEPTOR - GALLUS GALLUS (CHICKEN).

MSHR_CHICK Melanocyte-stimulating hormone receptor (MSH-R) (Melanotropin receptor) (Melanocortin receptor 1) (MC1-R) - Gallus gallus (Chicken).
Scan History
OWL27_1    2  50   NSINGLE    
SPTR37_9f 2 15 NSINGLE
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
YYESTYVVVC MC5R_SHEEP 180 180 -
YSDSSAVIIC MC4R_HUMAN 187 187 -
YYESKYVIVC MC5R_RAT 180 180 -
YSESKMVIVC MC3R_MOUSE 182 182 -
YSESKMVIVC MC3R_HUMAN 219 219 -

Motif 2 width=14
Element Seqn Id St Int Rpt
IAMFLTMLLLMASL MC5R_SHEEP 191 1 -
ITMFFTMLALMASL MC4R_HUMAN 198 1 -
ISMFFTMLFFMVSL MC5R_RAT 191 1 -
ITMFFAMVLLMGTL MC3R_MOUSE 193 1 -
ITMFFAMMLLMGTL MC3R_HUMAN 230 1 -

Motif 3 width=12
Element Seqn Id St Int Rpt
RTHVRRIAALPG MC5R_SHEEP 213 8 -
RLHIKRIAVLPG MC4R_HUMAN 220 8 -
RNHVKRIAASPR MC5R_RAT 213 8 -
RLHVQRIAVLPP MC3R_MOUSE 215 8 -
RLHVKRIAALPP MC3R_HUMAN 252 8 -

Motif 4 width=9
Element Seqn Id St Int Rpt
LILMISCPQ MC5R_SHEEP 258 33 -
LIFYISCPQ MC4R_HUMAN 265 33 -
LILMISCPQ MC5R_RAT 258 33 -
LVLIITCPT MC3R_MOUSE 262 35 -
LVLIITCPT MC3R_HUMAN 299 35 -

Motif 5 width=11
Element Seqn Id St Int Rpt
FMSHFNMYLIL MC5R_SHEEP 273 6 -
FMSHFNLYLIL MC4R_HUMAN 280 6 -
FMSYFNMYLIL MC5R_RAT 273 6 -
YTAHFNTYLVL MC3R_MOUSE 277 6 -
YTAHFNTYLVL MC3R_HUMAN 314 6 -

Motif 6 width=8
Element Seqn Id St Int Rpt
KTFKEIVC MC5R_SHEEP 304 20 -
KTFKEIIC MC4R_HUMAN 311 20 -
RTFKEIIC MC5R_RAT 304 20 -
NTFKEILC MC3R_MOUSE 308 20 -
NTFREILC MC3R_HUMAN 345 20 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
YYESTYVIIC O73671 180 180 -
YYESTYVVVC MC5R_SHEEP 180 180 -
YSESKTVIVC O93259 182 182 -
YSDSSAVIIC MC4R_HUMAN 187 187 -
YYESKYVIVC MC5R_RAT 180 180 -
YSESTYVILC MC5R_HUMAN 180 180 -
YYESKYVIIC MC5R_MOUSE 180 180 -
YSDSSAVIIC MC4R_RAT 187 187 -
YYESTYVVIC MC5R_BOVIN 180 180 -
YSDSSVVIIC O73667 186 186 -
YSESKMVIVC MC3R_RAT 182 182 -
YSESKMVIVC MC3R_MOUSE 182 182 -
YSESKMVIVC MC3R_HUMAN 219 219 -

Motif 2 width=14
Element Seqn Id St Int Rpt
ITMFFTMLFLMVSL O73671 191 1 -
IAMFLTMLLLMASL MC5R_SHEEP 191 1 -
ITMFFTMLFLMASL O93259 193 1 -
ITMFFTMLALMASL MC4R_HUMAN 198 1 -
ISMFFTMLFFMVSL MC5R_RAT 191 1 -
ISMFFAMLFLLVSL MC5R_HUMAN 191 1 -
ISMFFTMLFFMVSL MC5R_MOUSE 191 1 -
ITMFFTMLVLMASL MC4R_RAT 198 1 -
IAMFLTMLLLMASL MC5R_BOVIN 191 1 -
ISMFFTMLILMASL O73667 197 1 -
ITMFFAMVLLMGTL MC3R_RAT 193 1 -
ITMFFAMVLLMGTL MC3R_MOUSE 193 1 -
ITMFFAMMLLMGTL MC3R_HUMAN 230 1 -

Motif 3 width=12
Element Seqn Id St Int Rpt
RTHVKKIAALPG O73671 213 8 -
RTHVRRIAALPG MC5R_SHEEP 213 8 -
RLHVKRIAALPV O93259 215 8 -
RLHIKRIAVLPG MC4R_HUMAN 220 8 -
RNHVKRIAASPR MC5R_RAT 213 8 -
RTHVKRIAALPG MC5R_HUMAN 213 8 -
RNHVKRIAASPR MC5R_MOUSE 213 8 -
RLHIKRIAVLPG MC4R_RAT 220 8 -
RTHIRRIATLPG MC5R_BOVIN 213 8 -
RMHIKKIAVLPG O73667 219 8 -
RLHVQRIAALPP MC3R_RAT 215 8 -
RLHVQRIAVLPP MC3R_MOUSE 215 8 -
RLHVKRIAALPP MC3R_HUMAN 252 8 -

Motif 4 width=9
Element Seqn Id St Int Rpt
LILMISCPQ O73671 258 33 -
LILMISCPQ MC5R_SHEEP 258 33 -
LILIISCPM O93259 260 33 -
LIFYISCPQ MC4R_HUMAN 265 33 -
LILMISCPQ MC5R_RAT 258 33 -
LTLMLSCPQ MC5R_HUMAN 258 33 -
LILMISCPQ MC5R_MOUSE 258 33 -
LLFYISCPQ MC4R_RAT 265 33 -
LILMISCPH MC5R_BOVIN 258 33 -
LIFYISCPY O73667 264 33 -
LVLIITCPT MC3R_RAT 262 35 -
LVLIITCPT MC3R_MOUSE 262 35 -
LVLIITCPT MC3R_HUMAN 299 35 -

Motif 5 width=11
Element Seqn Id St Int Rpt
FMSHFNMYLIL O73671 273 6 -
FMSHFNMYLIL MC5R_SHEEP 273 6 -
YTSHFNTYLVL O93259 275 6 -
FMSHFNLYLIL MC4R_HUMAN 280 6 -
FMSYFNMYLIL MC5R_RAT 273 6 -
FMSHFNMYLIL MC5R_HUMAN 273 6 -
FMSYFNMYLIL MC5R_MOUSE 273 6 -
FMSHFNLYLIL MC4R_RAT 280 6 -
FMSHFNMYLIL MC5R_BOVIN 273 6 -
FMSHFNFYLIL O73667 279 6 -
YTAHFNTYLVL MC3R_RAT 277 6 -
YTAHFNTYLVL MC3R_MOUSE 277 6 -
YTAHFNTYLVL MC3R_HUMAN 314 6 -

Motif 6 width=8
Element Seqn Id St Int Rpt
KTFKEIIC O73671 304 20 -
KTFKEIVC MC5R_SHEEP 304 20 -
KTFKEIVC O93259 306 20 -
KTFKEIIC MC4R_HUMAN 311 20 -
RTFKEIIC MC5R_RAT 304 20 -
KTFKEIIC MC5R_HUMAN 304 20 -
RTFKEIVC MC5R_MOUSE 304 20 -
KTFKEIIC MC4R_RAT 311 20 -
KTFKEIVC MC5R_BOVIN 304 20 -
KTFKEIIC O73667 310 20 -
NTFKEILC MC3R_RAT 308 20 -
NTFKEILC MC3R_MOUSE 308 20 -
NTFREILC MC3R_HUMAN 345 20 -