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PR01150

Identifier
MELATONIN1CR  [View Relations]  [View Alignment]  
Accession
PR01150
No. of Motifs
5
Creation Date
21-MAY-1999
Title
Melatonin 1C receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00857 MELATONINR
INTERPRO; IPR002279
GCRDB; GCR_1080; GCR_0935
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.
Melatonin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp192-193.
 
7. REPPERT, S.M., WEAVER, D.R., CASSONE, V.M., GODSON, C. AND 
KOLAKOWSKI, L.F.
Melatonin receptors are for the birds: molecular analysis of two receptor
subtypes differentially expressed in chick brain.
NEURON 15(5) 1003-15 (1995).

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].
 
Melatonin is secreted by the pineal gland during darkness [6]. It regulates
a variety of neuroendocrine functions and is thought to play an essential
role in circadian rhythms [6]. Drugs that modify the action of melatonin,
and hence influence circadian cycles, are of clinical interest (for example,
in the treatment of jet-lag) [6]. Melatonin receptors are found in the 
retina, in the pars tuberalis of the pituitary, and in discrete areas of 
the brain. The receptor inhibits adenylyl cyclase via a pertussis-toxin-
sensitive G protein, probably of the Gi/Go class [6]. 
 
Three sub-types have been cloned, designated Mel1a, Mel1b and Mel1c,
together with a closely related orphan receptor, termed Mel1x. Chick brain
and Xenopus Mel1c receptors are 80% identical and are distinct from the 
Mel1a and Mel1b subtypes [7]. Similar ligand binding and functional 
characteristics are observed in expressed Mel1a and Mel1c receptors [7].
The widespread distribution of Mel1a and Mel1c mRNA in brain provides a
molecular substrate for the profound actions of melatonin in birds [7]. 
 
MELATONIN1CR is a 5-element fingerprint that provides a signature for the
melatonin 1C 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 areas of the alignment
that characterise the melatonin 1C receptors but distinguish them from the
rest of the melatonin receptor family - motif 1 resides at the N-terminus;
motif 2 lies in the N-terminal portion of TM domain 1; motif 3 spans the 
third cytoplasmic loop; and motifs 4 and 5 reside at the C-terminus. A 
single iteration on SPTR37_9f was required to reach convergence, no further
sequences being identified beyond the starting set. A single partial match
was found, a melatonin 1A receptor that matches motifs 2 and 5.
Summary Information
   4 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
544444
400000
300000
201001
12345
True Positives
ML1C_CHICK    ML1C_XENLA    P87496        P87499        
True Positive Partials
Codes involving 2 elements
ML1A_HUMAN
Sequence Titles
ML1C_CHICK  MELATONIN RECEPTOR TYPE 1C (MEL-1C-R) (CKB) - GALLUS GALLUS (CHICKEN). 
ML1C_XENLA MELATONIN RECEPTOR TYPE 1C (MEL-1C-R) - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
P87496 MEL-1C(B) MELATONIN RECEPTOR - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
P87499 MEL-1C(A) MELATONIN RECEPTOR - XENOPUS LAEVIS (AFRICAN CLAWED FROG).

ML1A_HUMAN MELATONIN RECEPTOR TYPE 1A (MEL-1A-R) - HOMO SAPIENS (HUMAN).
Scan History
SPTR37_9f  1  100  NSINGLE    
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
EVNSTCLDCRTP ML1C_XENLA 3 3 -
GSNGSCSGCRLE ML1C_CHICK 5 5 -

Motif 2 width=8
Element Seqn Id St Int Rpt
SALAVVLI ML1C_XENLA 33 18 -
SGLAAVLI ML1C_CHICK 25 8 -

Motif 3 width=13
Element Seqn Id St Int Rpt
RQDFKQKLTQTDL ML1C_XENLA 227 186 -
RQDCKQKIRAADI ML1C_CHICK 219 186 -

Motif 4 width=16
Element Seqn Id St Int Rpt
TPRLLFLDTSRGGTEG ML1C_XENLA 320 80 -
TPRLLFIDVSKGGTEG ML1C_CHICK 312 80 -

Motif 5 width=17
Element Seqn Id St Int Rpt
GLKSKPSPAVTNNNQAD ML1C_XENLA 335 -1 -
GLKSKPSPAVTNNNQAE ML1C_CHICK 327 -1 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
EVNSTCLDCRTP ML1C_XENLA 3 3 -
EVNSTCLDCRTP P87499 3 3 -
EVNSTCLDCRTP P87496 3 3 -
GSNGSCSGCRLE ML1C_CHICK 5 5 -

Motif 2 width=8
Element Seqn Id St Int Rpt
SALAVVLI ML1C_XENLA 33 18 -
SALAVVLI P87499 33 18 -
SALAVVLI P87496 33 18 -
SGLAAVLI ML1C_CHICK 25 8 -

Motif 3 width=13
Element Seqn Id St Int Rpt
RQDFKQKLTQTDL ML1C_XENLA 227 186 -
RQDFKQKLTQTDL P87499 227 186 -
RQDFKQKLTPTDL P87496 227 186 -
RQDCKQKIRAADI ML1C_CHICK 219 186 -

Motif 4 width=16
Element Seqn Id St Int Rpt
TPRLLFLDTSRGGTEG ML1C_XENLA 320 80 -
TPRLLFLDTSRGGTEG P87499 320 80 -
TPRLLFLDTSRGGTEG P87496 320 80 -
TPRLLFIDVSKGGTEG ML1C_CHICK 312 80 -

Motif 5 width=17
Element Seqn Id St Int Rpt
GLKSKPSPAVTNNNQAD ML1C_XENLA 335 -1 -
GLKSKPSPAVTNNNQAD P87499 335 -1 -
GLKSKPSPAVTNNNQAD P87496 335 -1 -
GLKSKPSPAVTNNNQAE ML1C_CHICK 327 -1 -