SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR00524

Identifier
CCYSTOKNINAR  [View Relations]  [View Alignment]  
Accession
PR00524
No. of Motifs
7
Creation Date
04-JUN-1996  (UPDATE 06-JUN-1999)
Title
Cholecystokinin type A receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN

INTERPRO; IPR000596
GCRDB; GCR_0646; GCR_0649; GCR_0355
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.
Cholecystokinin (CCK) and gastrin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.89-95.

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]. 
 
Cholecystokinins (CCKs) and gastrins are naturally-occurring peptides that
share a common C-terminal sequence, GWMDF; full biological activity resides
in this region [6]. In the periphery, the principal physiological actions
of CCK include gall bladder contraction, pancreatic enzyme secretion and
regulation of secretion/absorption in the gastrointestinal tract [6]. In
the CNS, CCK induces analgesia, satiety and a decrease in exploratory
behaviour. In mesolimbic and mesocortical neurons, CCK coexists with
dopamine [6]. It is found throughout the digestive tract, with high
concentrations in the duodenum and jejunum. It is also found in peripheral
nerves to other smooth muscles and to secretory glands, and is one of the
most abundant peptides in the brain [6]. The highest levels of the CCKA
receptor are found in peripheral tissues, notably the pancreas, stomach,
intestine and gall bladder [6]. It has only a limited distribution in the
brain. The receptor has been implicated in the pathogenesis of schizo-
phrenia, Parkinson's disease, drug addiction and feeding disorders.
 
CCYSTOKNINAR is a 7-element fingerprint that provides a signature for the
cholecystokinin type A receptors. The fingerprint was derived from an
initial alignment of 4 sequences: the motifs were drawn from conserved
sections within either loop or N- and C-terminal regions, focusing on
those areas of the alignment that characterise the CCKA receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motif 1
lies at the N-terminus; motif 2 spans the second external loop; motifs 3-5
spans the third cytoplasmic loop; and motifs 6 and 7 lie at the C-terminus. 
A single iteration on OWL28.0 was required to reach convergence, no further
sequence being identified beyond the starting set.
 
An update on SPTR37_9f identified a true set of 4 sequences.
Summary Information
4 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
74444444
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
CCKR_CAVPO    CCKR_HUMAN    CCKR_RAT      O08786        
Sequence Titles
CCKR_CAVPO  Cholecystokinin type A receptor (CCK-A receptor) (CCK-AR) - Cavia porcellus (Guinea pig). 
CCKR_HUMAN Cholecystokinin type A receptor (CCK-A receptor) (CCK-AR) - Homo sapiens (Human).
CCKR_RAT Cholecystokinin type A receptor (CCK-A receptor) (CCK-AR) - Rattus norvegicus (Rat).
O08786 CHOLECYSTOKININ A RECEPTOR (CHOLECYSTOKININ TYPE-A RECEPTOR) - MUS MUSCULUS (MOUSE).
Scan History
OWL28_0    1  100  NSINGLE    
SPTR37_9f 2 5 NSINGLE
Initial Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
LGLDNETLFCLDQPPPSKEWQ S50150 20 20 -
LGFENETLFCLDRPRPSKEWQ S68242 20 20 -
LGLENETLFCLDQPQPSKEWQ CCKR_RAT 35 35 -
LGLENETLFCLDQPRPSKEWQ CCKR_HUMAN 20 20 -

Motif 2 width=19
Element Seqn Id St Int Rpt
SNLVPFTKNNNQTGNMCRF S68242 180 139 -
SNLVPFTKNNNQTANMCRF CCKR_RAT 195 139 -
SNLVPFTKNNNQTANMCRF CCKR_HUMAN 180 139 -
SNLVPFTKTNNQTANMCRF S50150 180 139 -

Motif 3 width=20
Element Seqn Id St Int Rpt
IKFDASQKKSAKERKASTGS S50150 240 41 -
IKFDAIQKKSAKERKTSTGS S68242 240 41 -
IKFEASQKKSAKERKPSTTS CCKR_HUMAN 240 41 -
IKFDASQKKSAKEKKPSTGS CCKR_RAT 255 41 -

Motif 4 width=17
Element Seqn Id St Int Rpt
YLQKSRHPRKLELRQLS S68242 270 10 -
YLQKSRPPRKLELQQLS CCKR_RAT 285 10 -
YLQKTRPPRKLELRQLS CCKR_HUMAN 270 10 -
YLQRSKPTRQLELQQLS S50150 269 9 -

Motif 5 width=17
Element Seqn Id St Int Rpt
RINRIRSSSSTANLMAK S68242 294 7 -
RVSRIHSSSSAAALMAK S50150 291 5 -
RLNRIRSSSSAANLIAK CCKR_RAT 308 6 -
RANRIRSNSSAANLMAK CCKR_HUMAN 292 5 -

Motif 6 width=14
Element Seqn Id St Int Rpt
PNPGPPGARGEVGE CCKR_HUMAN 389 80 -
PNPGTPGVRGEMGE S68242 391 80 -
PNPGPPGPRAEAGE S50150 388 80 -
PNPGPPGVRGEVGE CCKR_RAT 405 80 -

Motif 7 width=12
Element Seqn Id St Int Rpt
EEEGGTTGASLS CCKR_HUMAN 403 0 -
EEEGRTTGASLS S68242 405 0 -
EEDGRTIRALLS CCKR_RAT 419 0 -
EEEGRTTRASLS S50150 402 0 -
Final Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
LGLENETLFCLDQPQPSKEWQ CCKR_RAT 35 35 -
LGLENETLFCLDQPQPSKEWQ O08786 20 20 -
LGLENETLFCLDQPRPSKEWQ CCKR_HUMAN 20 20 -
LGFENETLFCLDRPRPSKEWQ CCKR_CAVPO 20 20 -

Motif 2 width=19
Element Seqn Id St Int Rpt
SNLVPFTKNNNQTANMCRF CCKR_RAT 195 139 -
SNLVPFTKNNNQTANMCRF O08786 180 139 -
SNLVPFTKNNNQTANMCRF CCKR_HUMAN 180 139 -
SNLVPFTKNNNQTGNMCRF CCKR_CAVPO 180 139 -

Motif 3 width=20
Element Seqn Id St Int Rpt
IKFDASQKKSAKEKKPSTGS CCKR_RAT 255 41 -
IKFDASQKKSAKEKRLSSGG O08786 240 41 -
IKFEASQKKSAKERKPSTTS CCKR_HUMAN 240 41 -
IKFDAIQKKSAKERKTSTGS CCKR_CAVPO 240 41 -

Motif 4 width=17
Element Seqn Id St Int Rpt
YLQKSRPPRKLELQQLS CCKR_RAT 285 10 -
YLQKSRPPRKLELQQLS O08786 277 17 -
YLQKTRPPRKLELRQLS CCKR_HUMAN 270 10 -
YLQKSRHPRKLELRQLS CCKR_CAVPO 270 10 -

Motif 5 width=17
Element Seqn Id St Int Rpt
RLNRIRSSSSAANLIAK CCKR_RAT 308 6 -
RINRIRSSGSAANLIAK O08786 300 6 -
RANRIRSNSSAANLMAK CCKR_HUMAN 292 5 -
RINRIRSSSSTANLMAK CCKR_CAVPO 294 7 -

Motif 6 width=14
Element Seqn Id St Int Rpt
PNPGPPGVRGEVGE CCKR_RAT 405 80 -
PNPGPTGVRGEVGE O08786 397 80 -
PNPGPPGARGEVGE CCKR_HUMAN 389 80 -
PNPGTPGVRGEMGE CCKR_CAVPO 391 80 -

Motif 7 width=12
Element Seqn Id St Int Rpt
EEDGRTIRALLS CCKR_RAT 419 0 -
EEDGRTIRASLS O08786 411 0 -
EEEGGTTGASLS CCKR_HUMAN 403 0 -
EEEGRTTGASLS CCKR_CAVPO 405 0 -