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PR01533

Identifier
CYSLTRECPTR  [View Relations]  [View Alignment]  
Accession
PR01533
No. of Motifs
6
Creation Date
23-MAY-2001
Title
Cysteinyl leukotriene receptor family signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01902 CYSLT1RECPTR; PR01903 CYSLT2RECPTR
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).

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, due 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].
 
CYSLTRECPTR is a 6-element fingerprint that provides a signature for the
cysteinyl leukotriene receptor family. The fingerprint was derived from an 
initial alignment of 3 sequences: the motifs were drawn from conserved 
sections within N- and C-terminal and loop regions, focusing on those areas
of the alignment that characterise the cysteinyl leukotriene receptors 
but distinguish them from the rest of the rhodopsin-like superfamily - motif 
1 lies in the N-terminus, leading into TM domain 1; motif 2 encodes the 
first cytoplasmic loop; motif 3 spans the first external loop; motif 4 lies 
in the second cytoplasmic loop, leading into TM domain 4; motif 5 is located
in the second external loop; and motif 6 resides at the C-terminus. Two 
iterations on SPTR39_15f were required to reach convergence, at which point
a true set comprising 4 sequences was identified.
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
Q9JJ71        Q9JK47        Q9NS75        Q9Y271        
Sequence Titles
Q9JJ71      CYSLT1 (CYSTEINYL LEUKOTRIENE 1 RECEPTOR SHORT ISOFORM) - Mus musculus (Mouse). 
Q9JK47 LEUKOTRIENE D4 RECEPTOR - Mus musculus (Mouse).
Q9NS75 CYSTEINYL LEUKOTRIENE CYSLT2 RECEPTOR - Homo sapiens (Human).
Q9Y271 CYSTEINYL LEUKOTRIENE RECEPTOR - Homo sapiens (Human).
Scan History
SPTR39_15f 2  120  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
TIDEFRNQVYSTMY Q9JK47 32 32 -
TIDDFRNQVYSTLY Q9Y271 17 17 -
TIENFKREFFPIVY Q9NS75 32 32 -

Motif 2 width=10
Element Seqn Id St Int Rpt
IKTYHEKSAF Q9JK47 64 18 -
IKTYHKKSAF Q9Y271 49 18 -
LQPYKKSTSV Q9NS75 64 18 -

Motif 3 width=25
Element Seqn Id St Int Rpt
RVVYYVHKGKWLFGDFLCRLTTYAL Q9JK47 94 20 -
RVVYYVHKGIWLFGDFLCRLSTYAL Q9Y271 79 20 -
RADYYLRGSNWIFGDLACRIMSYSL Q9NS75 94 20 -

Motif 4 width=14
Element Seqn Id St Int Rpt
QNINLVTQKKARFV Q9JK47 145 26 -
QNINLVTQKKARFV Q9Y271 130 26 -
FRLLHVTSIRSAWI Q9NS75 144 25 -

Motif 5 width=15
Element Seqn Id St Int Rpt
NNTKCFEPPQNNQAK Q9JK47 184 25 -
NNTKCFEPPQDNQTK Q9Y271 169 25 -
SVTSCLELNLYKIAK Q9NS75 183 25 -

Motif 6 width=12
Element Seqn Id St Int Rpt
NFRRRLSTFRKH Q9JK47 316 117 -
NFRKRLSTFRKH Q9Y271 301 117 -
NFKDRLKSALRK Q9NS75 311 113 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
TIDEFRNQVYSTMY Q9JJ71 19 19 -
TIDEFRNQVYSTMY Q9JK47 32 32 -
TIDDFRNQVYSTLY Q9Y271 17 17 -
TIENFKREFFPIVY Q9NS75 32 32 -

Motif 2 width=10
Element Seqn Id St Int Rpt
IKTYHEKSAF Q9JJ71 51 18 -
IKTYHEKSAF Q9JK47 64 18 -
IKTYHKKSAF Q9Y271 49 18 -
LQPYKKSTSV Q9NS75 64 18 -

Motif 3 width=25
Element Seqn Id St Int Rpt
RVVYYVHKGKWLFGDFLCRLTTYAL Q9JJ71 81 20 -
RVVYYVHKGKWLFGDFLCRLTTYAL Q9JK47 94 20 -
RVVYYVHKGIWLFGDFLCRLSTYAL Q9Y271 79 20 -
RADYYLRGSNWIFGDLACRIMSYSL Q9NS75 94 20 -

Motif 4 width=14
Element Seqn Id St Int Rpt
QNINLVTQKKARFV Q9JJ71 132 26 -
QNINLVTQKKARFV Q9JK47 145 26 -
QNINLVTQKKARFV Q9Y271 130 26 -
FRLLHVTSIRSAWI Q9NS75 144 25 -

Motif 5 width=15
Element Seqn Id St Int Rpt
NNTKCFEPPQNNQAK Q9JJ71 171 25 -
NNTKCFEPPQNNQAK Q9JK47 184 25 -
NNTKCFEPPQDNQTK Q9Y271 169 25 -
SVTSCLELNLYKIAK Q9NS75 183 25 -

Motif 6 width=12
Element Seqn Id St Int Rpt
NFRRRLSTFRKH Q9JJ71 303 117 -
NFRRRLSTFRKH Q9JK47 316 117 -
NFRKRLSTFRKH Q9Y271 301 117 -
NFKDRLKSALRK Q9NS75 311 113 -