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PR01149

Identifier
MELATONIN1AR  [View Relations]  [View Alignment]  
Accession
PR01149
No. of Motifs
6
Creation Date
21-MAY-1999
Title
Melatonin 1A receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00857 MELATONINR
INTERPRO; IPR002278
GCRDB; GCR_1650; GCR_1552; GCR_1583; GCR_2032; GCR_1081
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. ROCA, A.L., GODSON, C., WEAVER, D.R. AND REPPERT, S.M.
Structure, characterization, and expression of the gene encoding the mouse 
Mel1a melatonin receptor.
ENDOCRINOLOGY 137(8) 3469-77 (1996).

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. The Mel1a
receptor appears to mediate the circadian and reproductive effects of the
hormone [7]. In situ hybridisation indicates that Mel1a receptor messenger
RNA is expressed in the hypothalamic suprachiasmatic nuclei and hypophyseal
pars tuberalis, presumed sites of the circadian and some of reproductive 
actions of melatonin, respectively [7].
 
MELATONIN1AR is a 6-element fingerprint that provides a signature for the
melatonin 1A receptors. The fingerprint was derived from an initial
alignment of 5 sequences: the motifs were drawn from conserved regions 
spanning the full alignment length, focusing on those areas of the alignment
that characterise the melatonin 1A receptors but distinguish them from the
rest of the melatonin receptor family - motifs 1 and 2 span the N-terminus,
leading into TM domain 1; motif 3 lies in the third cytoplasmic loop; motif 
4 spans part of the third external loop; and motifs 5 and 6 reside at the
C-terminus. Two iterations on SPTR37_9f were required to reach convergence,
at which point a true set comprising 6 sequences was identified. Three 
partial matches were also found, melatonin 1C receptors that match motifs
2 and 6.
Summary Information
   6 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
3 codes involving 2 elements
Composite Feature Index
6666666
5000000
4000000
3000000
2030003
123456
True Positives
ML1A_CHICK    ML1A_HUMAN    ML1A_MOUSE    ML1A_PHOSU    
ML1A_SHEEP O46608
True Positive Partials
Codes involving 2 elements
ML1C_XENLA P87496 P87499
Sequence Titles
ML1A_CHICK  MELATONIN RECEPTOR TYPE 1A (MEL-1A-R) (CKA) - GALLUS GALLUS (CHICKEN). 
ML1A_HUMAN MELATONIN RECEPTOR TYPE 1A (MEL-1A-R) - HOMO SAPIENS (HUMAN).
ML1A_MOUSE MELATONIN RECEPTOR TYPE 1A (MEL-1A-R) - MUS MUSCULUS (MOUSE).
ML1A_PHOSU MELATONIN RECEPTOR TYPE 1A (MEL-1A-R) - PHODOPUS SUNGORUS (STRIPED HAIRY-FOOTED HAMSTER) (DJUNGARIAN HAMSTER).
ML1A_SHEEP MELATONIN RECEPTOR TYPE 1A (MEL-1A-R) - OVIS ARIES (SHEEP).
O46608 MEL 1A MELATONIN RECEPTOR - OVIS ARIES (SHEEP).

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).
Scan History
SPTR37_9f  2  100  NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
SELLNATQQAPGGGEG ML1A_MOUSE 6 6 -
STLLNASQQAPGVGEG ML1A_PHOSU 6 6 -
SALLNVSQAAPGAGDG ML1A_SHEEP 19 19 -
GSALPNASQPVLRGDG ML1A_HUMAN 5 5 -
SELNGTVLPRDPPAEG ML1A_CHICK 6 6 -

Motif 2 width=15
Element Seqn Id St Int Rpt
RPSWLASTLAFILIF ML1A_MOUSE 25 3 -
RPSWLASTLAFILIF ML1A_PHOSU 25 3 -
RPSWLAATLASILIF ML1A_SHEEP 38 3 -
RPSWLASALACVLIF ML1A_HUMAN 22 1 -
RPPWVTSTLATILIF ML1A_CHICK 25 3 -

Motif 3 width=13
Element Seqn Id St Int Rpt
KPDNKPKLKPQDF ML1A_MOUSE 225 185 -
KPDSKPRLKPQDF ML1A_PHOSU 225 185 -
KPDNKPKLKPQDF ML1A_SHEEP 238 185 -
KPDRKPKLKPQDF ML1A_HUMAN 222 185 -
KPDNNPRLKPHDF ML1A_CHICK 225 185 -

Motif 4 width=10
Element Seqn Id St Int Rpt
VASDPATMVP ML1A_MOUSE 264 26 -
VASDPATMAP ML1A_PHOSU 264 26 -
VASDPASMAP ML1A_SHEEP 277 26 -
VASDPASMVP ML1A_HUMAN 261 26 -
VAVDPETIIP ML1A_CHICK 264 26 -

Motif 5 width=16
Element Seqn Id St Int Rpt
KMFFVESSNEEADKIK ML1A_MOUSE 320 46 -
KMCFVDSSNDPADKIK ML1A_PHOSU 320 46 -
KMFFVDSSNHVADRIK ML1A_SHEEP 333 46 -
RVFFVDSSNDVADRVK ML1A_HUMAN 317 46 -
KAFFQDSSNDAADRIR ML1A_CHICK 320 46 -

Motif 6 width=16
Element Seqn Id St Int Rpt
KPSPLIPNNNLIKVDS ML1A_MOUSE 337 1 -
KPAPLIANNNLIKVDS ML1A_PHOSU 337 1 -
KPSPLIANHNLIKVDS ML1A_SHEEP 350 1 -
KPSPLMTNNNVVKVDS ML1A_HUMAN 334 1 -
KPSPLITNNNQVKVDS ML1A_CHICK 337 1 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
SELLNATQQAPGGGEG ML1A_MOUSE 6 6 -
STLLNASQQAPGVGEG ML1A_PHOSU 6 6 -
SALLNVSQAAPGAGDG ML1A_SHEEP 19 19 -
SALLNVSQAAPGAGDG O46608 19 19 -
GSALPNASQPVLRGDG ML1A_HUMAN 5 5 -
SELNGTVLPRDPPAEG ML1A_CHICK 6 6 -

Motif 2 width=15
Element Seqn Id St Int Rpt
RPSWLASTLAFILIF ML1A_MOUSE 25 3 -
RPSWLASTLAFILIF ML1A_PHOSU 25 3 -
RPSWLAATLASILIF ML1A_SHEEP 38 3 -
RPSWLAATLASILIF O46608 38 3 -
RPSWLASALACVLIF ML1A_HUMAN 22 1 -
RPPWVTSTLATILIF ML1A_CHICK 25 3 -

Motif 3 width=13
Element Seqn Id St Int Rpt
KPDNKPKLKPQDF ML1A_MOUSE 225 185 -
KPDSKPRLKPQDF ML1A_PHOSU 225 185 -
KPDNKPKLKPQDF ML1A_SHEEP 238 185 -
KPDNKPKLKPQDF O46608 238 185 -
KPDRKPKLKPQDF ML1A_HUMAN 222 185 -
KPDNNPRLKPHDF ML1A_CHICK 225 185 -

Motif 4 width=10
Element Seqn Id St Int Rpt
VASDPATMVP ML1A_MOUSE 264 26 -
VASDPATMAP ML1A_PHOSU 264 26 -
VASDPASMAP ML1A_SHEEP 277 26 -
VASDPDSMAP O46608 277 26 -
VASDPASMVP ML1A_HUMAN 261 26 -
VAVDPETIIP ML1A_CHICK 264 26 -

Motif 5 width=16
Element Seqn Id St Int Rpt
KMFFVESSNEEADKIK ML1A_MOUSE 320 46 -
KMCFVDSSNDPADKIK ML1A_PHOSU 320 46 -
KMFFVDSSNHVADRIK ML1A_SHEEP 333 46 -
KMFFVDSSNHVADRIK O46608 333 46 -
RVFFVDSSNDVADRVK ML1A_HUMAN 317 46 -
KAFFQDSSNDAADRIR ML1A_CHICK 320 46 -

Motif 6 width=16
Element Seqn Id St Int Rpt
KPSPLIPNNNLIKVDS ML1A_MOUSE 337 1 -
KPAPLIANNNLIKVDS ML1A_PHOSU 337 1 -
KPSPLIANHNLIKVDS ML1A_SHEEP 350 1 -
KPSPLIANRNLVKVDS O46608 350 1 -
KPSPLMTNNNVVKVDS ML1A_HUMAN 334 1 -
KPSPLITNNNQVKVDS ML1A_CHICK 337 1 -