SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR01903

Identifier
CYSLT2RECPTR  [View Relations]  [View Alignment]  
Accession
PR01903
No. of Motifs
6
Creation Date
21-FEB-2003
Title
Cysteinyl leukotriene receptor 2 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. TAKASAKI, J., KAMOHARA, M., MATSUMOTO, M., SAITO, T., SUGIMOTO, T.,
OHISHI, T., ISHII, H., OTA, T., NISHIKAWA, T., KAWAI, Y., MASUHO, Y.,
ISOGAI, T., SUZUKI, Y., SUGANO, S. AND FURUICHI, K.
The molecular characterization and tissue distribution of the human
cysteinyl leukotriene CysLT(2) receptor.
BIOCHEM.BIOPHYS.RES.COMMUN. 274(2) 316-322 (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].
 
CysLT2 has highest affinities for LTC4 and LTD4 and, upon activation,
stimulates phosphatidyl inositol hydrolysis leading to increased
intracellular calcium concentration. The receptor is expressed widely, with
highest levels in the heart, placenta, spleen, peripheral blood leukocytes
and adrenal gland [9-11].
 
CYSLT2RECPTR is a 6-element fingerprint that provides a signature for
cysteinyl leukotriene receptor 2. The fingerprint was derived from an  
initial alignment of 4 sequences: the motifs were drawn from conserved
sections within loop, TM and N-terminal regions, focusing on those areas of
the alignment that characterise cysteinyl leukotriene receptor 2 but
distinguish it from the rest of the leukotriene receptor family - motif 1
lies at the N-terminus; motif 2 is located in the second external loop;
motifs 3 and 4 span the third cytoplasmic loop, leading into TM domain 6;
motif 5 encodes the C-terminal portion of TM domain 6; and motif 6 resides
in the third external loop. Two iterations on SPTR40_22f were required to
reach convergence, at which point a true set comprising 5 sequences was
identified.
Summary Information
5 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
6555555
5000000
4000000
3000000
2000000
123456
True Positives
CLT2_HUMAN    CLT2_MOUSE    CLT2_PIG      CLT2_RAT      
Q8R528
Sequence Titles
CLT2_HUMAN                                                
CLT2_MOUSE Cysteinyl leukotriene receptor 2 (CysLTR2) - Mus musculus (Mouse).
CLT2_PIG Cysteinyl leukotriene receptor 2 (CysLTR2) - Sus scrofa (Pig).
CLT2_RAT Cysteinyl leukotriene receptor 2 (CysLTR2) (RSBPT32) - Rattus norvegicus (Rat).
Q8R528 Cysteinyl leukotriene 2 receptor - Mus musculus (Mouse).
Scan History
SPTR40_22f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
TGTPSSYSNRNCT CLT2_MOUSE 4 4 -
TGTPSYYSDKNCT CLT2_RAT 4 4 -
NGTFSNNNSRNCT CLT2_HUMAN 20 20 -
STLGNHNSNRSCT CLT2_PIG 21 21 -

Motif 2 width=11
Element Seqn Id St Int Rpt
SSALLLVNGQE CLT2_MOUSE 153 136 -
SSGLLLKHGQE CLT2_RAT 153 136 -
SSIMLLDSGSE CLT2_HUMAN 169 136 -
SSTVLLKNGSE CLT2_PIG 170 136 -

Motif 3 width=13
Element Seqn Id St Int Rpt
IIRILLKAEIPES CLT2_MOUSE 208 44 -
IIRVLLKVEIPES CLT2_RAT 208 44 -
IIRVLLKVEVPES CLT2_HUMAN 224 44 -
IIRALLKVEVPES CLT2_PIG 225 44 -

Motif 4 width=13
Element Seqn Id St Int Rpt
GPRAAHRKALTTI CLT2_MOUSE 221 0 -
GPRDAQRKALTTI CLT2_RAT 221 0 -
GLRVSHRKALTTI CLT2_HUMAN 237 0 -
GLRLSHRKALITV CLT2_PIG 238 0 -

Motif 5 width=12
Element Seqn Id St Int Rpt
YHALRTLHLVTW CLT2_MOUSE 247 13 -
YHALRTIHLVTW CLT2_RAT 247 13 -
YHTLRTVHLTTW CLT2_HUMAN 263 13 -
YHVLRTLHLLEW CLT2_PIG 264 13 -

Motif 6 width=12
Element Seqn Id St Int Rpt
CGDVLHKATVIT CLT2_MOUSE 263 4 -
CMDELHKATVIT CLT2_RAT 263 4 -
CKDRLHKALVIT CLT2_HUMAN 279 4 -
CKDRLHKAVAVT CLT2_PIG 280 4 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
TGTPSSYSNRNCT CLT2_MOUSE 4 4 -
TGTPSSYSNRNCT Q8R528 4 4 -
TGTPSYYSDKNCT CLT2_RAT 4 4 -
NGTFSNNNSRNCT CLT2_HUMAN 20 20 -
STLGNHNSNRSCT CLT2_PIG 21 21 -

Motif 2 width=11
Element Seqn Id St Int Rpt
SSALLLVNGQE CLT2_MOUSE 153 136 -
SSALLLVNGQE Q8R528 153 136 -
SSGLLLKHGQE CLT2_RAT 153 136 -
SSIMLLDSGSE CLT2_HUMAN 169 136 -
SSTVLLKNGSE CLT2_PIG 170 136 -

Motif 3 width=13
Element Seqn Id St Int Rpt
IIRILLKAEIPES CLT2_MOUSE 208 44 -
IIRILLKAEIPES Q8R528 208 44 -
IIRVLLKVEIPES CLT2_RAT 208 44 -
IIRVLLKVEVPES CLT2_HUMAN 224 44 -
IIRALLKVEVPES CLT2_PIG 225 44 -

Motif 4 width=13
Element Seqn Id St Int Rpt
GPRAAHRKALTTI CLT2_MOUSE 221 0 -
GPRAAHRKALTTI Q8R528 221 0 -
GPRDAQRKALTTI CLT2_RAT 221 0 -
GLRVSHRKALTTI CLT2_HUMAN 237 0 -
GLRLSHRKALITV CLT2_PIG 238 0 -

Motif 5 width=12
Element Seqn Id St Int Rpt
YHALRTLHLVTW CLT2_MOUSE 247 13 -
YHALRTLHLVTW Q8R528 247 13 -
YHALRTIHLVTW CLT2_RAT 247 13 -
YHTLRTVHLTTW CLT2_HUMAN 263 13 -
YHVLRTLHLLEW CLT2_PIG 264 13 -

Motif 6 width=12
Element Seqn Id St Int Rpt
CGDVLHKATVIT CLT2_MOUSE 263 4 -
CGDVLHKATVIT Q8R528 263 4 -
CMDELHKATVIT CLT2_RAT 263 4 -
CKDRLHKALVIT CLT2_HUMAN 279 4 -
CKDRLHKAVAVT CLT2_PIG 280 4 -