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PR01151

Identifier
MELATONIN1XR  [View Relations]  [View Alignment]  
Accession
PR01151
No. of Motifs
12
Creation Date
21-MAY-1999
Title
Melatonin-related 1X receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00857 MELATONINR
INTERPRO; IPR002280
GCRDB; GCR_1930
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., EBISAWA, T., MAHLE, C.D. AND KOLAKOWSKI, L.F. 
Cloning of a melatonin-related receptor from human pituitary.
FEBS LETT. 386 219-24 (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. Mel1x from 
human pituitary is a protein of 613 amino acids that is 45% identical to
human Mel1a and Mel1b receptors [7]. Although closely related to the 
melatonin receptor family, the sequence is unusual in lacking N-linked
glycosylation sites and in bearing a >300 residue C-terminal tail. The
receptor does not bind [125I]melatonin or [3H]melatonin [7]. Its mRNA is 
expressed in hypothalamus and pituitary, suggesting that the receptor and 
its natural ligand are involved in neuroendocrine function [7]. 
 
MELATONIN1XR is a 12-element fingerprint that provides a signature for 
melatonin-related 1X 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 areas of the alignment
that characterise the melatonin-related 1X receptors but distinguish them 
from the melatonin receptor family - motifs 1 and 2 span the N-terminus,
leading into TM domain 1; motif 3 lies in the first external loop; motif 4
lies in the second external loop; motif 5 resides in the third cytoplasmic
loop; and motifs 6-12 span the C-terminus. A single iteration on SPTR37_9f 
was required to reach convergence, no further sequences being identified 
beyond the starting set. 
Summary Information
3 codes involving 12 elements
0 codes involving 11 elements
0 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
12333333333333
11000000000000
10000000000000
9000000000000
8000000000000
7000000000000
6000000000000
5000000000000
4000000000000
3000000000000
2000000000000
123456789101112
True Positives
ML1X_HUMAN    ML1X_MOUSE    ML1X_SHEEP    
Sequence Titles
ML1X_HUMAN  MELATONIN-RELATED RECEPTOR (H9) - HOMO SAPIENS (HUMAN). 
ML1X_MOUSE MELATONIN-RELATED RECEPTOR - MUS MUSCULUS (MOUSE).
ML1X_SHEEP MELATONIN-RELATED RECEPTOR (H9) - OVIS ARIES (SHEEP).
Scan History
SPTR37_9f  1  100  NSINGLE    
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
GPTLAVPTPYGCIGCKLPQ ML1X_HUMAN 2 2 -
GPTKAVPTPFGCIGCKLPK ML1X_MOUSE 2 2 -
GRTLAVPTPYGCIGCKLPQ ML1X_SHEEP 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
PEYPPALIIFMFC ML1X_HUMAN 21 0 -
PDYPPALIIFMFC ML1X_MOUSE 21 0 -
PDYPPALIVFMFC ML1X_SHEEP 21 0 -

Motif 3 width=14
Element Seqn Id St Int Rpt
HAMSIGGWDLSQLQ ML1X_HUMAN 87 53 -
YAMSVGGWDLSQLQ ML1X_MOUSE 87 53 -
HAMAIGGWDLSKLQ ML1X_SHEEP 87 53 -

Motif 4 width=12
Element Seqn Id St Int Rpt
IFNYLNNPVFTV ML1X_HUMAN 179 78 -
IFNYVNNPAFTV ML1X_MOUSE 179 78 -
IFNYVNNPAFAV ML1X_SHEEP 179 78 -

Motif 5 width=20
Element Seqn Id St Int Rpt
KVLAARDPAGQNPDNQLAEV ML1X_HUMAN 214 23 -
KVLAARDPAGQNPDNQFAEV ML1X_MOUSE 214 23 -
KVLAARDPAGQNPDNQLAEV ML1X_SHEEP 214 23 -

Motif 6 width=13
Element Seqn Id St Int Rpt
WTIFHAMRHPIIF ML1X_HUMAN 306 72 -
WTIFHAMRHPILF ML1X_MOUSE 306 72 -
WTIFHAMRHPVLF ML1X_SHEEP 306 72 -

Motif 7 width=16
Element Seqn Id St Int Rpt
LISDIREMQEARTLAR ML1X_HUMAN 322 3 -
LISDIRETWETRALTR ML1X_MOUSE 322 3 -
LLTDVREMQEAQAHTH ML1X_SHEEP 322 3 -

Motif 8 width=19
Element Seqn Id St Int Rpt
ARAHARDQAREQDRAHACP ML1X_HUMAN 338 0 -
ARVRARDQVREQERARACV ML1X_MOUSE 338 0 -
ARARARTQAHEQDHAHACP ML1X_SHEEP 338 0 -

Motif 9 width=16
Element Seqn Id St Int Rpt
AVEETPMNVRNVPLPG ML1X_HUMAN 357 0 -
AVEGTPRNVRNVLLPG ML1X_MOUSE 357 0 -
AVEEIPMSVRNVPLPG ML1X_SHEEP 357 0 -

Motif 10 width=24
Element Seqn Id St Int Rpt
HSKAASGHLKPVSGHSKPASGHPK ML1X_HUMAN 410 37 -
HHKSISGHPKSASVYPKPASSVHC ML1X_MOUSE 403 30 -
HPKPASGHSRSVSARRKSASAHPK ML1X_SHEEP 385 12 -

Motif 11 width=17
Element Seqn Id St Int Rpt
HAEPTTADYPKPATTSH ML1X_HUMAN 508 74 -
HPATTTVDYLEPATTSH ML1X_MOUSE 488 61 -
HSEPTTLDYLEPITTSH ML1X_SHEEP 480 71 -

Motif 12 width=13
Element Seqn Id St Int Rpt
DYHDVVVVDVEDD ML1X_HUMAN 595 70 -
DYRKVVLIDDDSD ML1X_MOUSE 561 56 -
DYHEIVLIDVDAD ML1X_SHEEP 557 60 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
GPTLAVPTPYGCIGCKLPQ ML1X_HUMAN 2 2 -
GPTKAVPTPFGCIGCKLPK ML1X_MOUSE 2 2 -
GRTLAVPTPYGCIGCKLPQ ML1X_SHEEP 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
PEYPPALIIFMFC ML1X_HUMAN 21 0 -
PDYPPALIIFMFC ML1X_MOUSE 21 0 -
PDYPPALIVFMFC ML1X_SHEEP 21 0 -

Motif 3 width=14
Element Seqn Id St Int Rpt
HAMSIGGWDLSQLQ ML1X_HUMAN 87 53 -
YAMSVGGWDLSQLQ ML1X_MOUSE 87 53 -
HAMAIGGWDLSKLQ ML1X_SHEEP 87 53 -

Motif 4 width=12
Element Seqn Id St Int Rpt
IFNYLNNPVFTV ML1X_HUMAN 179 78 -
IFNYVNNPAFTV ML1X_MOUSE 179 78 -
IFNYVNNPAFAV ML1X_SHEEP 179 78 -

Motif 5 width=20
Element Seqn Id St Int Rpt
KVLAARDPAGQNPDNQLAEV ML1X_HUMAN 214 23 -
KVLAARDPAGQNPDNQFAEV ML1X_MOUSE 214 23 -
KVLAARDPAGQNPDNQLAEV ML1X_SHEEP 214 23 -

Motif 6 width=13
Element Seqn Id St Int Rpt
WTIFHAMRHPIIF ML1X_HUMAN 306 72 -
WTIFHAMRHPILF ML1X_MOUSE 306 72 -
WTIFHAMRHPVLF ML1X_SHEEP 306 72 -

Motif 7 width=16
Element Seqn Id St Int Rpt
LISDIREMQEARTLAR ML1X_HUMAN 322 3 -
LISDIRETWETRALTR ML1X_MOUSE 322 3 -
LLTDVREMQEAQAHTH ML1X_SHEEP 322 3 -

Motif 8 width=19
Element Seqn Id St Int Rpt
ARAHARDQAREQDRAHACP ML1X_HUMAN 338 0 -
ARVRARDQVREQERARACV ML1X_MOUSE 338 0 -
ARARARTQAHEQDHAHACP ML1X_SHEEP 338 0 -

Motif 9 width=16
Element Seqn Id St Int Rpt
AVEETPMNVRNVPLPG ML1X_HUMAN 357 0 -
AVEGTPRNVRNVLLPG ML1X_MOUSE 357 0 -
AVEEIPMSVRNVPLPG ML1X_SHEEP 357 0 -

Motif 10 width=24
Element Seqn Id St Int Rpt
HSKAASGHLKPVSGHSKPASGHPK ML1X_HUMAN 410 37 -
HHKSISGHPKSASVYPKPASSVHC ML1X_MOUSE 403 30 -
HPKPASGHSRSVSARRKSASAHPK ML1X_SHEEP 385 12 -

Motif 11 width=17
Element Seqn Id St Int Rpt
HAEPTTADYPKPATTSH ML1X_HUMAN 508 74 -
HPATTTVDYLEPATTSH ML1X_MOUSE 488 61 -
HSEPTTLDYLEPITTSH ML1X_SHEEP 480 71 -

Motif 12 width=13
Element Seqn Id St Int Rpt
DYHDVVVVDVEDD ML1X_HUMAN 595 70 -
DYRKVVLIDDDSD ML1X_MOUSE 561 56 -
DYHEIVLIDVDAD ML1X_SHEEP 557 60 -