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PR01902

Identifier
CYSLT1RECPTR  [View Relations]  [View Alignment]  
Accession
PR01902
No. of Motifs
6
Creation Date
21-FEB-2003
Title
Cysteinyl leukotriene receptor 1 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01533 CYSLTRECPTR
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.
Leukotrienes.
IN THE G protein-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994,
PP.181-187.
 
7. SARAU, H.M., AMES, R.S., CHAMBERS, J., ELLIS, C., ELSHOURBAGY, N.,
FOLEY, J.J., SCHMIDT, D.B., MUCCITELLI, R.M., JENKINS, O., MURDOCK, P.R.,
HERRITY, N.C., HALSEY, W., SATHE, G., MUIR, A.I., NUTHULAGANTI, P., 
DYTKO, G.M., BUCKLEY, P.T., WILSON, S., BERGSMA, D.J. AND HAY, D.W.
Identification, molecular cloning, expression, and characterization of a
cysteinyl leukotriene receptor.
MOL.PHARMACOL. 56 657-663 (1999).
 
8. FIGUEROA, D.J., BREYER, R.M., DEFOE, S.K., KARGMAN, S., DAUGHERTY, B.L.,
WALDBURGER, K., LIU, Q., CLEMENTS, M., ZENG, Z., O'NEILL, G.P., JONES, T.R.,
LYNCH, K.R., AUSTIN, C.P. AND EVANS, J.F.
Expression of the cysteinyl leukotriene 1 receptor in normal human lung and
peripheral blood leukocytes.
AM.J.RESPIR.CRIT.CARE MED. 163 226-233 (2001).
 
9. NOTHACKER, H.-P., WANG, Z., ZHU, Y., REINSCHEID, R.K., LIN, S.H.S. AND
CIVELLI, O.
Molecular cloning and characterization of a second human cysteinyl
leukotriene receptor: discovery of a subtype selective agonist.
MOL.PHARMACOL. 58 1601-1608 (2000).
 
10. HEISE, C.E., O'DOWD, B.F., FIGUEROA, D.J., SAWYER, N., NGUYEN, T.,
IM, D.S., STOCCO, R., BELLEFEUILLE, J.N., ABRAMOVITZ, M., CHENG, R.,
WILLIAMS, D.L., ZENG, Z., LIU, Q., MA, L., CLEMENTS, M.K., COULOMBE, N.,
LIU, Y., AUSTIN, C.P., GEORGE, S.R., O'NEILL, G.P., METTERS, K.M.,
LYNCH, K.R. AND EVANS, J.F.
Characterization of the human cysteinyl leukotriene 2 receptor.
J.BIOL.CHEM. 275(39) 30531-30536 (2000).
 
11. LYNCH, K.R., O'NEILL, G.P., LIU, Q., IM, D.S., SAWYER, N.,
METTERS, K.M., COULOMBE, N., ABRAMOVITZ, M., FIGUEROA, D.J., ZENG, Z.,
CONNOLLY, B.M., BAI, C., AUSTIN, C.P., CHATEAUNEUF, A., STOCCO, R., 
GREIG, G.M., KARGMAN, S., HOOKS, S.B., HOSFIELD, E., WILLIAMS, D.L.JR.,
FORD-HUTCHINSON, A.W., CASKEY, C.T. AND EVANS, J.F.
Characterization of the human cysteinyl leukotriene CysLT1 receptor.
NATURE 399 789-793 (1999).

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].
 
Leukotrienes (LT) are potent lipid mediators derived from arachidonic acid
metabolism. They can be divided into two classes based on the presence or
absence of a cysteinyl group. Leukotriene B4 (LTB4) does not contain such a
group, whereas LTC4, LTD4, LTE4 and LTF4 are cysteinyl leukotrienes [6].
 
Cysteinyl leukotrienes (CysLTs), previously known as the "slow reacting
substance of anaphylaxis", are produced predominantly by myeloid cells
associated with inflammatory responses [9]. They are the most potent
bronchoconstrictors known and also have pro-inflammatory effects, making
them important mediators in the pathophysiology of human asthma [8]. CysLTs
have also been implicated in a variety of other diseases, such as allergic
rhinitis, inflammatory bowel disease and psoriasis [9]. Pharmacological
studies of the effects of CysLTs have provided evidence for the existence of
at least 2 distinct receptor subtypes, belonging to the G protein-coupled
receptor family, designated CysLT1 and CysLT2 [7,8]. CysLT1 is thought to
mediate bronchospasm, plasma exudation, vasoconstriction, mucus secretion
and eosinophil recruitment [8]. CysLT2 is less well defined, owing to a lack
of specific agonists and antagonists, but is thought to mediate some of the
vascular effects attributed to CysLTs [8,9]. Both receptor subtypes have now
been cloned [7,10].
 
CysLT1 has a much higher affinity for LTD4 than for the other cysteinyl
leukotrienes and, upon activation, stimulates phosphatidyl inositol
hydrolysis and increases in intracellular calcium. The receptor is expressed
at highest levels in the spleen and in peripheral blood leukocytes, with 
lower levels in the lung, placenta, small intestine, pancreas, colon and 
heart [7,8,11].
 
CYSLT1RECPTR is a 6-element fingerprint that provides a signature for
cysteinyl leukotriene receptor 1. The fingerprint was derived from an
initial alignment of 4 sequences: the motifs were drawn from conserved
sections within loop, TM and C-terminal regions, focusing on those areas of
the alignment that characterise cysteinyl leukotriene receptor 1 but
distinguish it from the rest of the cysteinyl leukotriene receptor family -
motif 1 encodes the C-terminal portion of TM domain 4, leading into the
second external loop; motif 2 lies at the N-terminus of TM domain 5; motif 3
is located in the third cytoplasmic loop; motifs 4 and 5 span the third
external loop; and motif 6 resides at the C-terminus. A single iteration on
SPTR40_22f was required to reach convergence, no further sequence being
identified beyond the starting set.
Summary Information
4 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
6444444
5000000
4000000
3000000
2000000
123456
True Positives
CLT1_HUMAN    CLT1_MOUSE    CLT1_PIG      CLT1_RAT      
Sequence Titles
CLT1_HUMAN                                                
CLT1_MOUSE
CLT1_PIG Cysteinyl leukotriene receptor 1 (CysLTR1) - Sus scrofa (Pig).
CLT1_RAT Cysteinyl leukotriene receptor 1 (CysLTR1) - Rattus norvegicus (Rat).
Scan History
SPTR40_22f 1  300  NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
TSSPFLLSKSYQDEKN CLT1_RAT 156 156 -
TSSPFLMYKSYQDEKN CLT1_MOUSE 169 169 -
TSSPFLMSTSYKDEKN CLT1_PIG 157 157 -
TSSPFLMAKPQKDEKN CLT1_HUMAN 154 154 -

Motif 2 width=10
Element Seqn Id St Int Rpt
YVLVLHYVSL CLT1_RAT 187 15 -
YVLILHYVSL CLT1_MOUSE 200 15 -
HVLVLHYVSL CLT1_PIG 188 15 -
HVLVLHYVSL CLT1_HUMAN 185 15 -

Motif 3 width=16
Element Seqn Id St Int Rpt
KNTMKKNLPSRRKAIG CLT1_RAT 220 23 -
KNTMKKNMPSRRKAIG CLT1_MOUSE 233 23 -
KNSMKKNISSRKKAIG CLT1_PIG 221 23 -
KKSMKKNLSSHKKAIG CLT1_HUMAN 218 23 -

Motif 4 width=11
Element Seqn Id St Int Rpt
IHLHFLHSETR CLT1_RAT 257 21 -
IHLHLLHSETR CLT1_MOUSE 270 21 -
IHLHFLHNDTK CLT1_PIG 258 21 -
IHLHFLHNETK CLT1_HUMAN 255 21 -

Motif 5 width=11
Element Seqn Id St Int Rpt
CDSVLRMQKSV CLT1_RAT 269 1 -
CDSVLRMQKSV CLT1_MOUSE 282 1 -
CDSVLRMQKSV CLT1_PIG 270 1 -
CDSVLRMQKSV CLT1_HUMAN 267 1 -

Motif 6 width=18
Element Seqn Id St Int Rpt
SLSSMTYIPKKKASLPEK CLT1_RAT 315 35 -
SLSSMTYVPKKKASLPEK CLT1_MOUSE 328 35 -
SLSTMTYVPKKKTSLPEK CLT1_PIG 316 35 -
SLSSVTYVPRKKASLPEK CLT1_HUMAN 313 35 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
TSSPFLLSKSYQDEKN CLT1_RAT 156 156 -
TSSPFLMYKSYQDEKN CLT1_MOUSE 169 169 -
TSSPFLMSTSYKDEKN CLT1_PIG 157 157 -
TSSPFLMAKPQKDEKN CLT1_HUMAN 154 154 -

Motif 2 width=10
Element Seqn Id St Int Rpt
YVLVLHYVSL CLT1_RAT 187 15 -
YVLILHYVSL CLT1_MOUSE 200 15 -
HVLVLHYVSL CLT1_PIG 188 15 -
HVLVLHYVSL CLT1_HUMAN 185 15 -

Motif 3 width=16
Element Seqn Id St Int Rpt
KNTMKKNLPSRRKAIG CLT1_RAT 220 23 -
KNTMKKNMPSRRKAIG CLT1_MOUSE 233 23 -
KNSMKKNISSRKKAIG CLT1_PIG 221 23 -
KKSMKKNLSSHKKAIG CLT1_HUMAN 218 23 -

Motif 4 width=11
Element Seqn Id St Int Rpt
IHLHFLHSETR CLT1_RAT 257 21 -
IHLHLLHSETR CLT1_MOUSE 270 21 -
IHLHFLHNDTK CLT1_PIG 258 21 -
IHLHFLHNETK CLT1_HUMAN 255 21 -

Motif 5 width=11
Element Seqn Id St Int Rpt
CDSVLRMQKSV CLT1_RAT 269 1 -
CDSVLRMQKSV CLT1_MOUSE 282 1 -
CDSVLRMQKSV CLT1_PIG 270 1 -
CDSVLRMQKSV CLT1_HUMAN 267 1 -

Motif 6 width=18
Element Seqn Id St Int Rpt
SLSSMTYIPKKKASLPEK CLT1_RAT 315 35 -
SLSSMTYVPKKKASLPEK CLT1_MOUSE 328 35 -
SLSTMTYVPKKKTSLPEK CLT1_PIG 316 35 -
SLSSVTYVPRKKASLPEK CLT1_HUMAN 313 35 -