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PR00362

Identifier
CANNABINOIDR  [View Relations]  [View Alignment]  
Accession
PR00362
No. of Motifs
9
Creation Date
05-JUL-1995  (UPDATE 06-JUN-1999)
Title
Cannabinoid receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00522 CANABINOID1R; PR00523 CANABINOID2R
INTERPRO; IPR002230
GCRDB; GCR_0055; GCR_0645
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.
Cannabinoid.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.80-83.

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]. 
 
The ability of marijuana to activate the cannabinoid receptor provides a
molecular explanation for its psychoactive effects and other CNS actions
(which include hallucinations, memory deficits, altered time and space
perception, CNS depression and appetite stimulation) [6]. The endogenous
ligand at the cannabinoid receptor is unknown, although it may be a
derivative of arachidonic acid. The cannabinoid receptor is widespread
throughout the CNS, high levels occurring in the dendate gyrus, hippocampus
and cerebral cortex, with more moderate levels in the hypothalamus and
amygdala. It is also present in various cell lines, and in the periphery
it is found in the testis and vas deferens [6].
 
CANNABINOIDR is a 9-element fingerprint that provides a signature for the
cannabinoid receptors. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved sections   
within either loop or TM regions, focusing on those areas of the 
alignment that characterise the cannabinoid receptors but distinguish them
from the rest of the rhodopsin-like superfamily - motif 1 lies in the 
N-terminal region immediately preceding TM domain 1; motif 2 spans the
central portion of TM domain 1; motif 3 lies in the first cytoplasmic loop;
motif 4 spans the C-terminus of TM domain 2 and the first external loop;
motif 5 lies in the second external loop; motif 6 lies at the C-terminus of
TM domain 5; motif 7 was drawn from the third cytoplasmic loop; and motifs
8 and 9 lie at the N- and C-termini of TM domain 7. Two iterations on
OWL27.1 were required to reach convergence, at which point a true set
comprising 6 sequences was identfied. Several partial matches were also
found, all of which are members of the melanocortin/melanotropin receptor
family that match motifs 2 and 9.
 
An update on SPTR37_9f identified a true set of 9 sequences.
Summary Information
9 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
9999999999
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
CB1A_FUGRU    CB1B_FUGRU    CB1R_FELCA    CB1R_HUMAN    
CB1R_MOUSE CB1R_RAT CB2R_HUMAN CB2R_MOUSE
Q13949
Sequence Titles
CB1A_FUGRU  CANNABINOID RECEPTOR TYPE 1A - Fugu rubripes (Japanese pufferfish) (Takifugu rubripes). 
CB1B_FUGRU CANNABINOID RECEPTOR TYPE 1B - FUGU RUBRIPES (JAPANESE PUFFERFISH) (TAKIFUGU RUBRIPES).
CB1R_FELCA CANNABINOID RECEPTOR 1 (CB1) (CB-R) - FELIS SILVESTRIS CATUS (CAT).
CB1R_HUMAN CANNABINOID RECEPTOR 1 (CB1) (CB-R) (CANN6) - HOMO SAPIENS (HUMAN).
CB1R_MOUSE CANNABINOID RECEPTOR 1 (CB1) (CB-R) (BRAIN-TYPE CANNABINOID RECEPTOR) - MUS MUSCULUS (MOUSE).
CB1R_RAT CANNABINOID RECEPTOR 1 (CB1) (CB-R) (BRAIN-TYPE CANNABINOID RECEPTOR) - RATTUS NORVEGICUS (RAT).
CB2R_HUMAN CANNABINOID RECEPTOR 2 (CB2) (CB-2) (CX5) - HOMO SAPIENS (HUMAN).
CB2R_MOUSE CANNABINOID RECEPTOR 2 (CB2) (CB-2) - MUS MUSCULUS (MOUSE).
Q13949 CENTRAL CANNABINOID RECEPTOR - HOMO SAPIENS (HUMAN).
Scan History
OWL27_1    2  75   NSINGLE    
SPTR37_9f 2 10 NSINGLE
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
MECFMILNPSQQLA CB1R_RAT 106 106 -
IECFMVLNPSQQLA CB1R_HUMAN 105 105 -
MKDYMILSGPQKTA CB2R_HUMAN 22 22 -

Motif 2 width=14
Element Seqn Id St Int Rpt
LGTFTVLENLLVLC CB1R_RAT 127 7 -
LGTFTVLENLLVLC CB1R_HUMAN 126 7 -
LGLLSALENVAVLY CB2R_HUMAN 43 7 -

Motif 3 width=14
Element Seqn Id St Int Rpt
HSRSLRCRPSYHFI CB1R_RAT 144 3 -
HSRSLRCRPSYHFI CB1R_HUMAN 143 3 -
SSHQLRRKPSYLFI CB2R_HUMAN 60 3 -

Motif 4 width=23
Element Seqn Id St Int Rpt
FVYSFVDFHVFHRKDSPNVFLFK CB1R_RAT 171 13 -
FVYSFIDFHVFHRKDSRNVFLFK CB1R_HUMAN 170 13 -
FACSFVNFHVFHGVDSKAVFLLK CB2R_HUMAN 87 13 -

Motif 5 width=16
Element Seqn Id St Int Rpt
CSDIFPLIDETYLMFW CB1R_RAT 265 71 -
CSDIFPHIDETYLMFW CB1R_HUMAN 264 71 -
CSELFPLIPNDYLLSW CB2R_HUMAN 179 69 -

Motif 6 width=16
Element Seqn Id St Int Rpt
YAYMYILWKAHSHAVR CB1R_RAT 293 12 -
YAYMYILWKAHSHAVR CB1R_HUMAN 292 12 -
YTYGHVLWKAHQHVAS CB2R_HUMAN 207 12 -

Motif 7 width=15
Element Seqn Id St Int Rpt
VQVTRPDQARMDIRL CB1R_RAT 328 19 -
VQVTRPDQARMDIRL CB1R_HUMAN 327 19 -
RQVPGMARMRLDVRL CB2R_HUMAN 229 6 -

Motif 8 width=12
Element Seqn Id St Int Rpt
IKTVFAFCSMLC CB1R_RAT 376 33 -
IKTVFAFCSMLC CB1R_HUMAN 375 33 -
VKKAFAFCSMLC CB2R_HUMAN 277 33 -

Motif 9 width=11
Element Seqn Id St Int Rpt
YALRSKDLRHA CB1R_RAT 398 10 -
YALRSKDLRHA CB1R_HUMAN 397 10 -
YALRSGEIRSS CB2R_HUMAN 299 10 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
MECFMILNPSQQLA CB1R_MOUSE 106 106 -
MECFMILNPSQQLA CB1R_RAT 106 106 -
MECFMILNPSQQLA CB1R_FELCA 105 105 -
IECFMVLNPSQQLA CB1R_HUMAN 105 105 -
IECFMVLNPSQQLA Q13949 44 44 -
MECFMILTPSQQLA CB1A_FUGRU 104 104 -
MECFMILTPAQQLV CB1B_FUGRU 102 102 -
MKEYMILSSGQQIA CB2R_MOUSE 22 22 -
MKDYMILSGPQKTA CB2R_HUMAN 22 22 -

Motif 2 width=14
Element Seqn Id St Int Rpt
LGTFTVLENLLVLC CB1R_MOUSE 127 7 -
LGTFTVLENLLVLC CB1R_RAT 127 7 -
LGTFTVLENLLVLC CB1R_FELCA 126 7 -
LGTFTVLENLLVLC CB1R_HUMAN 126 7 -
LGTFTVLENLLVLC Q13949 65 7 -
LGTFTVLENLVVLC CB1A_FUGRU 125 7 -
LGTFTVLENFVVLC CB1B_FUGRU 123 7 -
MGLLSALENMAVLY CB2R_MOUSE 43 7 -
LGLLSALENVAVLY CB2R_HUMAN 43 7 -

Motif 3 width=14
Element Seqn Id St Int Rpt
HSRSLRCRPSYHFI CB1R_MOUSE 144 3 -
HSRSLRCRPSYHFI CB1R_RAT 144 3 -
HSRSLRCRPSYHFI CB1R_FELCA 143 3 -
HSRSLRCRPSYHFI CB1R_HUMAN 143 3 -
HSRSLRCRPSYHFI Q13949 82 3 -
QSRTLRCRPSYHFI CB1A_FUGRU 142 3 -
HSHTLRSRPSYHFI CB1B_FUGRU 140 3 -
SSRRLRRKPSYLFI CB2R_MOUSE 60 3 -
SSHQLRRKPSYLFI CB2R_HUMAN 60 3 -

Motif 4 width=23
Element Seqn Id St Int Rpt
FVYSFVDFHVFHRKDSPNVFLFK CB1R_MOUSE 171 13 -
FVYSFVDFHVFHRKDSPNVFLFK CB1R_RAT 171 13 -
FVYSFVDFHVFHRKDSPNVFLFK CB1R_FELCA 170 13 -
FVYSFIDFHVFHRKDSRNVFLFK CB1R_HUMAN 170 13 -
FVYSFIDFHVFHRKDSRNVFLFK Q13949 109 13 -
FVYSFLDFHVFHKKDSPNVFLFK CB1A_FUGRU 169 13 -
FVYSFLDFHVLHRKDSPSIFLFK CB1B_FUGRU 167 13 -
FACNFVIFHVFHGVDSNAIFLLK CB2R_MOUSE 87 13 -
FACSFVNFHVFHGVDSKAVFLLK CB2R_HUMAN 87 13 -

Motif 5 width=16
Element Seqn Id St Int Rpt
CSDIFPLIDETYLMFW CB1R_MOUSE 265 71 -
CSDIFPLIDETYLMFW CB1R_RAT 265 71 -
CSDIFPLIDETYLMFW CB1R_FELCA 264 71 -
CSDIFPHIDETYLMFW CB1R_HUMAN 264 71 -
CSDIFPHIDETYLMFW Q13949 203 71 -
CSDIFPLIDENYLMFW CB1A_FUGRU 263 71 -
CSDIFPLIDEKYLMFW CB1B_FUGRU 261 71 -
CSELFPLIPNDYLLGW CB2R_MOUSE 179 69 -
CSELFPLIPNDYLLSW CB2R_HUMAN 179 69 -

Motif 6 width=16
Element Seqn Id St Int Rpt
YAYMYILWKAHSHAVR CB1R_MOUSE 293 12 -
YAYMYILWKAHSHAVR CB1R_RAT 293 12 -
YAYMYILWKAHIHAVR CB1R_FELCA 292 12 -
YAYMYILWKAHSHAVR CB1R_HUMAN 292 12 -
YAYMYILWKAHSHAVR Q13949 231 12 -
YAYIYILWKAHHHAVR CB1A_FUGRU 291 12 -
YAYMFILWKSHHHAVR CB1B_FUGRU 289 12 -
YTYGYVLWKAHRHVAT CB2R_MOUSE 207 12 -
YTYGHVLWKAHQHVAS CB2R_HUMAN 207 12 -

Motif 7 width=15
Element Seqn Id St Int Rpt
VQVTRPDQARMDIRL CB1R_MOUSE 328 19 -
VQVTRPDQARMDIRL CB1R_RAT 328 19 -
VQVTRPDQARMDIRL CB1R_FELCA 327 19 -
VQVTRPDQARMDIRL CB1R_HUMAN 327 19 -
VQVTRPDQARMDIRL Q13949 266 19 -
VQTTRPEQTRMDIRL CB1A_FUGRU 326 19 -
VQTVRPEQARMDLRL CB1B_FUGRU 324 19 -
RQVPGIARMRLDVRL CB2R_MOUSE 229 6 -
RQVPGMARMRLDVRL CB2R_HUMAN 229 6 -

Motif 8 width=12
Element Seqn Id St Int Rpt
IKTVFAFCSMLC CB1R_MOUSE 376 33 -
IKTVFAFCSMLC CB1R_RAT 376 33 -
IKTVFAFCSMLC CB1R_FELCA 375 33 -
IKTVFAFCSMLC CB1R_HUMAN 375 33 -
IKTVFAFCSMLC Q13949 314 33 -
IKTVFAFCSMLC CB1A_FUGRU 374 33 -
IKTVFAFCSMLC CB1B_FUGRU 372 33 -
VKEAFAFCSMLC CB2R_MOUSE 277 33 -
VKKAFAFCSMLC CB2R_HUMAN 277 33 -

Motif 9 width=11
Element Seqn Id St Int Rpt
YALRSKDLRHA CB1R_MOUSE 398 10 -
YALRSKDLRHA CB1R_RAT 398 10 -
YALRSKDLRHA CB1R_FELCA 397 10 -
YALRSKDLRHA CB1R_HUMAN 397 10 -
YALRSKDLRHA Q13949 336 10 -
YALRSRDLRHA CB1A_FUGRU 396 10 -
YAMRSKDLRRA CB1B_FUGRU 394 10 -
YALRSGEIRSA CB2R_MOUSE 299 10 -
YALRSGEIRSS CB2R_HUMAN 299 10 -