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PR00857

Identifier
MELATONINR  [View Relations]  [View Alignment]  
Accession
PR00857
No. of Motifs
7
Creation Date
10-FEB-1998  (UPDATE 21-JUN-1999)
Title
Melatonin receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01149 MELATONIN1AR; PR01150 MELATONIN1CR; PR01151 MELATONIN1XR

INTERPRO; IPR000025
GCRDB; GCR_1650; GCR_1552; GCR_1583; GCR_2032; GCR_1081; GCR_1080

GCRDB; 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.

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]. 
 
MELATONINR is a 7-element fingerprint that provides a signature for the
melatonin receptors. The fingerprint was derived from an initial alignment
of 15 sequences: the motifs were drawn from conserved sections largely
within loop or TM regions, focusing on those areas of the alignment
that characterise the melatonin receptors but distinguish them from the
rest of the rhodopsin-like superfamily - motif 1 spans lies in the second
cytoplasmic loop, leading into TM domain 4; motifs 2 and 3 span the second
external loop, leading into TM domain 5; motifs 4 and 5 span the third
cytoplasmic loop, leading into TM domain 6; motif 6 lies at the C-terminus
of TM domain 6; and motif 7 spans the third external loop, leading into
TM domain 7. Two iterations on OWL29.6 were required to reach convergence,
at which point a true set comprising 19 sequences was identified. Several 
partial matches were also found, all of which are fragments and melatonin-
related receptor sequences that fail to match one or more motifs.
 
An update on SPTR37_9f identified a true set of 11 sequences, and 3
partial matches.
Summary Information
  11 codes involving  7 elements
0 codes involving 6 elements
0 codes involving 5 elements
2 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
711111111111111
60000000
50000000
42200202
31100100
20000000
1234567
True Positives
ML1A_CHICK    ML1A_HUMAN    ML1A_MOUSE    ML1A_PHOSU    
ML1A_SHEEP ML1B_HUMAN ML1C_CHICK ML1C_XENLA
O46608 P87496 P87499
True Positive Partials
Codes involving 4 elements
ML1X_HUMAN ML1X_MOUSE
Codes involving 3 elements
ML1X_SHEEP
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).
ML1B_HUMAN MELATONIN RECEPTOR TYPE 1B (MEL-1B-R) - HOMO SAPIENS (HUMAN).
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).
O46608 MEL 1A MELATONIN RECEPTOR - OVIS ARIES (SHEEP).
P87496 MEL-1C(B) MELATONIN RECEPTOR - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
P87499 MEL-1C(A) MELATONIN RECEPTOR - XENOPUS LAEVIS (AFRICAN CLAWED FROG).

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
OWL29_6    2  100  NSINGLE    
SPTR37_9f 2 50 NSINGLE
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
SMAYHRIYRRWHTPLH ML1B_HUMAN 145 145 -
SLRYDKLFNLKNTCCY ML1C_CHICK 129 129 -
SLRYDKLYNQRSTWCY ML1C_XENLA 137 137 -
SLKYDKLYSDKNSLCY ML1A_CHICK 135 135 -
SLKYDRLYSNKNSLCY ML1A_PHOSU 6 6 -
SLRYGKLYSGTNSLCY ML1A_SHEEP 148 148 -
SLKYDKLYSSKNSLCY ML1A_HUMAN 132 132 -
SLKYDKLFSNKNTVCY ML12_BRARE 3 3 -
SLKYDRIYSNKNSLCY ML1A_RAT 6 6 -
SLRYDRLYSRRNTCLY ML1C_BRARE 3 3 -
SFAYDKVYSCWNTMLY ML1B_CHICK 71 71 -
SSWYNRLFSNSGTICY ML1A_XENLA 2 2 -
SLKYDKLYSDKNSVCY ML11_BRARE 3 3 -
SFAYGRLCSFRNTLLL ML1B_BRARE 3 3 -

Motif 2 width=16
Element Seqn Id St Int Rpt
NLFVGSLRCDPRIFSC ML1A_XENLA 32 14 -
NLFVGSLQYDPRVYSC ML11_BRARE 33 14 -
NWFVESLQYDPRVFSC ML12_BRARE 33 14 -
NLQTGTLQYDPRIYSC ML1A_RAT 36 14 -
NFLVGSLKYDPRVFSC ML1C_BRARE 33 14 -
NFFVGSLKYDPRIYSC ML1B_CHICK 101 14 -
NFFVGSLSYDPRVYSC ML1B_BRARE 33 14 -
NLRAGTLQYDPRIYSC ML1A_HUMAN 162 14 -
NLCVGTLQYDPRIYSC ML1A_SHEEP 178 14 -
NLQTGTLQYDPRIYSC ML1A_PHOSU 36 14 -
NLFVGSLQYDPRIYSC ML1A_CHICK 165 14 -
NFFVGSLQYDPRIFSC ML1C_XENLA 167 14 -
NFFVGSLQYDPRIYSC ML1C_CHICK 159 14 -
NFFVGSLEYDPRIYSC ML1B_HUMAN 175 14 -

Motif 3 width=19
Element Seqn Id St Int Rpt
CTFIQTASTQYTAAVVVIH ML1B_HUMAN 190 -1 -
CTFAQTVSTSYTITVVVVH ML1C_CHICK 174 -1 -
CTFAQTVSSSYTITVVVVH ML1C_XENLA 182 -1 -
CTFAQSVSSAYTIAVVFFH ML1A_CHICK 180 -1 -
CTFTQSVSSAYTIAVVVFH ML1A_PHOSU 51 -1 -
CTFTQSVSSAYTIAVVVFH ML1A_SHEEP 193 -1 -
CTFAQSVSSAYTIAVVVFH ML1A_HUMAN 177 -1 -
CTFTQTASSSYTVVVVVVH ML1B_BRARE 48 -1 -
CTFAQYVSSYYTIAVVIFH ML1A_XENLA 47 -1 -
CTFVQTASSYYTIAVVVIH ML1B_CHICK 116 -1 -
CTFTQTASSSYTVCVVLIH ML1C_BRARE 48 -1 -
CTFTQSVSSAYTIALVVFH ML1A_RAT 51 -1 -
CTFAQSVSSLYTIMVVVVH ML12_BRARE 48 -1 -
CTFEQSASSAYTIAVVFFH ML11_BRARE 48 -1 -

Motif 4 width=15
Element Seqn Id St Int Rpt
VLQARRKAKPESRLC ML1B_HUMAN 227 18 -
VIQVKHRVRQDCKQK ML1C_CHICK 211 18 -
VIQVKHRVRQDFKQK ML1C_XENLA 219 18 -
VIQVRRRVKPDNNPR ML1A_CHICK 217 18 -
VLQVRRRVKPDSKPR ML1A_PHOSU 88 18 -
VLQVRWKVKPDNKPK ML1A_SHEEP 230 18 -
VLQVRQRVKPDRKPK ML1A_HUMAN 214 18 -
VIQVRRKVKSEERSR ML1B_BRARE 85 18 -
VLNIRHRVKPDRHLH ML1A_XENLA 84 18 -
VLQVRRRVKSETKPR ML1B_CHICK 153 18 -
VIRVKGRVRPNPKVR ML1C_BRARE 85 18 -
VLQVRRRVKPDSKPK ML1A_RAT 88 18 -
VIQVPRRVKPDSRPK ML12_BRARE 85 18 -
VIQVRRRVKNDNRPK ML11_BRARE 85 18 -

Motif 5 width=15
Element Seqn Id St Int Rpt
TQTDLRNFLTMFVVF ML1C_XENLA 235 1 -
KPHDFRNFLTMFVVF ML12_BRARE 101 1 -
KPQDFRNFVTMFVVF ML1A_RAT 104 1 -
RAADLRNFLTMFVVF ML1C_BRARE 99 -1 -
KPSDFRNFLTMFVVF ML1B_CHICK 169 1 -
WPYNIHGFITMFVVF ML1A_XENLA 102 3 -
RPSDLRNFVTMFVVF ML1B_BRARE 101 1 -
KPQDFRNFVTMFVVF ML1A_HUMAN 230 1 -
KPQDFRNFVTMFVVF ML1A_SHEEP 246 1 -
KPQDFRNFVTMFVVF ML1A_PHOSU 104 1 -
KPHDFRNFVTMFVVF ML1A_CHICK 233 1 -
TPHDVRNFVTMFVVF ML11_BRARE 101 1 -
RAADIRNFLTMFVVF ML1C_CHICK 227 1 -
KPSDLRSFLTMFVVF ML1B_HUMAN 243 1 -

Motif 6 width=11
Element Seqn Id St Int Rpt
NFIGLAVASDP ML1A_HUMAN 255 10 -
NFIGLVVASDP ML1A_SHEEP 271 10 -
NFIGLIVASDP ML1A_PHOSU 129 10 -
NFIGLAVAVDP ML1A_CHICK 258 10 -
NFIGLAVAINP ML1C_XENLA 260 10 -
NFIGLAVSINP ML1C_CHICK 252 10 -
NCIGLAVAINP ML1B_HUMAN 268 10 -
NLIGLVVAINP ML1B_BRARE 126 10 -
NIIGLTVAIYP ML1A_XENLA 127 10 -
NFIGLAVAINP ML1B_CHICK 194 10 -
NFIGLAVAINP ML1C_BRARE 124 10 -
NFIGLIVASDP ML1A_RAT 129 10 -
NFIGLAVAIHP ML12_BRARE 126 10 -
NFIGLAVAISP ML11_BRARE 126 10 -

Motif 7 width=13
Element Seqn Id St Int Rpt
VPRIPEWLFVASY ML1A_HUMAN 269 3 -
GDSIPQWLFVASY ML1A_XENLA 140 2 -
APKVPEWLFIISY ML1B_CHICK 208 3 -
APNIPEWLFVTSY ML1C_BRARE 138 3 -
APRIPEWLFVASY ML1A_RAT 143 3 -
GQSIPEWLFTASY ML12_BRARE 139 2 -
VPLIPEWLFVASY ML11_BRARE 140 3 -
APQIPEGLFVTSY ML1B_HUMAN 282 3 -
QPHIPEWLFVLSY ML1C_CHICK 266 3 -
APKIPEWLFVLSY ML1C_XENLA 274 3 -
IPRIPEWLFVSSY ML1A_CHICK 272 3 -
APRIPEWLFVASY ML1A_PHOSU 143 3 -
APRIPEWLFVASY ML1A_SHEEP 285 3 -
APRVPEWLFVVSY ML1B_BRARE 140 3 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
SLKYDKLYSSKNSLCY ML1A_HUMAN 132 132 -
SLRYGKLYSGTNSLCY ML1A_SHEEP 148 148 -
SLRYGKLYSGTNSLCY O46608 148 148 -
SLKYDRLYSNKNSLCY ML1A_PHOSU 6 6 -
SLKYDKIYSNKNSLCY ML1A_MOUSE 135 135 -
SLKYDKLYSDKNSLCY ML1A_CHICK 135 135 -
SLRYDKLYNQRSTWCY P87499 137 137 -
SLRYDKLYNQRSTWCY ML1C_XENLA 137 137 -
SLRYDKLFNQRSTWFY P87496 137 137 -
SLRYDKLFNLKNTCCY ML1C_CHICK 129 129 -
SMAYHRIYRRWHTPLH ML1B_HUMAN 145 145 -

Motif 2 width=16
Element Seqn Id St Int Rpt
NLRAGTLQYDPRIYSC ML1A_HUMAN 162 14 -
NLCVGTLQYDPRIYSC ML1A_SHEEP 178 14 -
NLCVGTLQYDPRIYSC O46608 178 14 -
NLQTGTLQYDPRIYSC ML1A_PHOSU 36 14 -
NLQTGTLQYDPRIYSC ML1A_MOUSE 165 14 -
NLFVGSLQYDPRIYSC ML1A_CHICK 165 14 -
NFFVGSLQYDPRIFSC P87499 167 14 -
NFFVGSLQYDPRIFSC ML1C_XENLA 167 14 -
NFFVGSLQYDPRIFSC P87496 167 14 -
NFFVGSLQYDPRIYSC ML1C_CHICK 159 14 -
NFFVGSLEYDPRIYSC ML1B_HUMAN 175 14 -

Motif 3 width=19
Element Seqn Id St Int Rpt
CTFAQSVSSAYTIAVVVFH ML1A_HUMAN 177 -1 -
CTFTQSVSSAYTIAVVVFH ML1A_SHEEP 193 -1 -
CTFTQSVSSAYTIAVVVFH O46608 193 -1 -
CTFTQSVSSAYTIAVVVFH ML1A_PHOSU 51 -1 -
CTFTQSVSSAYTIAVVVFH ML1A_MOUSE 180 -1 -
CTFAQSVSSAYTIAVVFFH ML1A_CHICK 180 -1 -
CTFAQTVSSSYTITVVVVH P87499 182 -1 -
CTFAQTVSSSYTITVVVVH ML1C_XENLA 182 -1 -
CTFAQTVSSSYTITVVVVH P87496 182 -1 -
CTFAQTVSTSYTITVVVVH ML1C_CHICK 174 -1 -
CTFIQTASTQYTAAVVVIH ML1B_HUMAN 190 -1 -

Motif 4 width=15
Element Seqn Id St Int Rpt
VLQVRQRVKPDRKPK ML1A_HUMAN 214 18 -
VLQVRWKVKPDNKPK ML1A_SHEEP 230 18 -
VLQVRWKVKPDNKPK O46608 230 18 -
VLQVRRRVKPDSKPR ML1A_PHOSU 88 18 -
VLQVRRRVKPDNKPK ML1A_MOUSE 217 18 -
VIQVRRRVKPDNNPR ML1A_CHICK 217 18 -
VIQVKHRVRQDFKQK P87499 219 18 -
VIQVKHRVRQDFKQK ML1C_XENLA 219 18 -
VIQVKHRVRQDFKQK P87496 219 18 -
VIQVKHRVRQDCKQK ML1C_CHICK 211 18 -
VLQARRKAKPESRLC ML1B_HUMAN 227 18 -

Motif 5 width=15
Element Seqn Id St Int Rpt
KPQDFRNFVTMFVVF ML1A_HUMAN 230 1 -
KPQDFRNFVTMFVVF ML1A_SHEEP 246 1 -
KPQDFRNFVTMFVVF O46608 246 1 -
KPQDFRNFVTMFVVF ML1A_PHOSU 104 1 -
KPQDFRNFVTMFVVF ML1A_MOUSE 233 1 -
KPHDFRNFVTMFVVF ML1A_CHICK 233 1 -
TQTDLRNFLTMFVVF P87499 235 1 -
TQTDLRNFLTMFVVF ML1C_XENLA 235 1 -
TPTDLRNFLTMFVVF P87496 235 1 -
RAADIRNFLTMFVVF ML1C_CHICK 227 1 -
KPSDLRSFLTMFVVF ML1B_HUMAN 243 1 -

Motif 6 width=11
Element Seqn Id St Int Rpt
NFIGLAVASDP ML1A_HUMAN 255 10 -
NFIGLVVASDP ML1A_SHEEP 271 10 -
NFIGLVVASDP O46608 271 10 -
NFIGLIVASDP ML1A_PHOSU 129 10 -
NLIGLIVASDP ML1A_MOUSE 258 10 -
NFIGLAVAVDP ML1A_CHICK 258 10 -
NFIGLAVAINP P87499 260 10 -
NFIGLAVAINP ML1C_XENLA 260 10 -
NFIGLAVAINP P87496 260 10 -
NFIGLAVSINP ML1C_CHICK 252 10 -
NCIGLAVAINP ML1B_HUMAN 268 10 -

Motif 7 width=13
Element Seqn Id St Int Rpt
VPRIPEWLFVASY ML1A_HUMAN 269 3 -
APRIPEWLFVASY ML1A_SHEEP 285 3 -
APRIPEWLFVASY O46608 285 3 -
APRIPEWLFVASY ML1A_PHOSU 143 3 -
VPRIPEWLFVASY ML1A_MOUSE 272 3 -
IPRIPEWLFVSSY ML1A_CHICK 272 3 -
APKIPEWLFVLSY P87499 274 3 -
APKIPEWLFVLSY ML1C_XENLA 274 3 -
APKIPEWLFVLSY P87496 274 3 -
QPHIPEWLFVLSY ML1C_CHICK 266 3 -
APQIPEGLFVTSY ML1B_HUMAN 282 3 -