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PR01478

Identifier
LTB2RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01478
No. of Motifs
7
Creation Date
14-MAR-2001
Title
Leukotriene B4 type 2 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01476 LTBRECEPTOR
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. YOKOMIZO, T., IZUMI, T. AND SHIMIZU, T.
Leukotriene B4: metabolism and signal transduction.
ARCH.BIOCHEM.BIOPHYS. 385(2) 231-241 (2001).
 
8. WANG, S., GUSTAFSON, E., PANG, L., QIAO, X., BEHAN, J., MAGUIRE, M.,
BAYNE, M. AND LAZ, T.
A novel hepatointestinal leukotriene B4 receptor.
J.BIOL.CHEM. 275(52) 40686-40694 (2000).
 
9. KAMOHARA, M., TAKASAKI, J., MATSUMOTO, M., SAITO, T., OHISHI, T., ISHII,
H. AND FURUICHI, K.
Molecular cloning and characterisation of another leukotriene B4 receptor.
J.BIOL.CHEM. 275(35) 27000-27004 (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].
 
LTB4 is one of the most effective chemoattractant mediators known, and is
produced predominantly by neutrophils and macrophages. It is involved in a
number of events, including: stimulation of leukocyte migration from the
bloodstream; activation of neutrophils; inflammatory pain; host defense
against infection; increased interleukin production and transcription [8].
It is found in elevated concentrations in a number of inflammatory and
allergic conditions, such as asthma, psoriasis, rheumatoid arthritis and
inflammatory bowel disease, and has been implicated in the pathogenesis of
these diseases [6,8].
 
Binding sites for LTB4 have been observed in membrane preparations from
leukocytes, macrophages and spleen. Two receptors for LTB4 have since been
cloned (BLT1 and BLT2); both are members of the rhodopsin-like G protein-
coupled receptor superfamily [7].
   
The leukotriene B4 type 2 receptor gene (BLT2) has been located in both the
human and mouse genomes, and is found in close proximity to BLT1 in both
species [7]. The receptor is expressed in most human tissues, with highest
levels in the liver, spleen, ovary and leukocytes [7,9]. Binding of LTB4 to
the receptor produces increased levels of inositol trisphosphate and calcium,
inhibition of forskolin-stimulated adenylyl cyclase activity and chemotaxis
[7,8]. These effects may be accomplished by coupling to G proteins of the
Gq, Gi and Gz classes [7].
 
LTB2RECEPTOR is a 7-element fingerprint that provides a signature for the
leukotriene B4 type 2 receptors. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved sections within
the N- and C-termini and loop regions, focusing on those areas of the alignment
that characterise the leukotriene B4 type 2 receptors but distinguish them from
the rest of the leukotriene B4 receptor family - motif 1 lies in the N-terminus;
motif 2 is located in the first cytoplasmic loop; motif 3 spans the C-terminus
of TM domain 4, leading into the second external loop; motif 4 lies in the third
cytoplasmic loop; motif 5 spans the third external loop, leading into TM domain 
7; and motifs 6 and 7 reside within the C-terminus. A single iteration on
SPTR39_15f was required to reach convergence, no further sequences being
identified beyond the starting set.
Summary Information
3 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
73333333
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
Q9JJL9        Q9NPC1        Q9NPE5        
Sequence Titles
Q9JJL9      LEUKOTRIENE B4 RECEPTOR, BLT2 - Mus musculus (Mouse). 
Q9NPC1 LEUKOTRIENE B4 RECEPTOR 2 (SEVEN TRANSMEMBRANE RECEPTOR BLTR2) - Homo sapiens (Human).
Q9NPE5 LEUKOTRIENE B4 RECEPTOR BLT2 (LTB4 RECEPTOR JULF2) - Homo sapiens (Human).
Scan History
SPTR39_15f 1  80   NSINGLE    
Initial Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
SVCYRPPGNETLLSWKTSRATGT Q9NPC1 33 33 -
SVCYRPPGNETLLSWKTSRATGT Q9NPE5 2 2 -
SVCYRPPGNETLLSWKGSRATGT Q9JJL9 2 2 -

Motif 2 width=15
Element Seqn Id St Int Rpt
WSLAGWRPARGRPLA Q9NPC1 74 18 -
WSLAGWRPARGRPLA Q9NPE5 43 18 -
WSLAGWRPTAGRPLA Q9JJL9 43 18 -

Motif 3 width=17
Element Seqn Id St Int Rpt
AAVYRHLWRDRVCQLCH Q9NPC1 187 98 -
AAVYRHLWRDRVCQLCH Q9NPE5 156 98 -
AAVYRHLWGGRVCQLCH Q9JJL9 156 98 -

Motif 4 width=18
Element Seqn Id St Int Rpt
RLRGARWGSGRHGARVGR Q9NPC1 238 34 -
RLRGARWGSGRHGARVGR Q9NPE5 207 34 -
RLRGARWGSGRQGTRVGR Q9JJL9 207 34 -

Motif 5 width=29
Element Seqn Id St Int Rpt
LQAVAALAPPEGALAKLGGAGQAARAGTT Q9NPC1 277 21 -
LQAVAALAPPEGALAKLGGAGQAARAGTT Q9NPE5 246 21 -
LQAVAALAPPEGPLARLGGAGQAARAGTT Q9JJL9 246 21 -

Motif 6 width=18
Element Seqn Id St Int Rpt
ARGGGRSREGTMELRTTP Q9NPC1 345 39 -
ARGGGRSREGTMELRTTP Q9NPE5 314 39 -
ARGGSRSREGTMELRTTP Q9JJL9 314 39 -

Motif 7 width=17
Element Seqn Id St Int Rpt
QLKVVGQGRGNGDPGGG Q9NPC1 363 0 -
QLKVVGQGRGNGDPGGG Q9NPE5 332 0 -
KLKVMGQGRGNGDPGGG Q9JJL9 332 0 -
Final Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
SVCYRPPGNETLLSWKTSRATGT Q9NPC1 33 33 -
SVCYRPPGNETLLSWKTSRATGT Q9NPE5 2 2 -
SVCYRPPGNETLLSWKGSRATGT Q9JJL9 2 2 -

Motif 2 width=15
Element Seqn Id St Int Rpt
WSLAGWRPARGRPLA Q9NPC1 74 18 -
WSLAGWRPARGRPLA Q9NPE5 43 18 -
WSLAGWRPTAGRPLA Q9JJL9 43 18 -

Motif 3 width=17
Element Seqn Id St Int Rpt
AAVYRHLWRDRVCQLCH Q9NPC1 187 98 -
AAVYRHLWRDRVCQLCH Q9NPE5 156 98 -
AAVYRHLWGGRVCQLCH Q9JJL9 156 98 -

Motif 4 width=18
Element Seqn Id St Int Rpt
RLRGARWGSGRHGARVGR Q9NPC1 238 34 -
RLRGARWGSGRHGARVGR Q9NPE5 207 34 -
RLRGARWGSGRQGTRVGR Q9JJL9 207 34 -

Motif 5 width=29
Element Seqn Id St Int Rpt
LQAVAALAPPEGALAKLGGAGQAARAGTT Q9NPC1 277 21 -
LQAVAALAPPEGALAKLGGAGQAARAGTT Q9NPE5 246 21 -
LQAVAALAPPEGPLARLGGAGQAARAGTT Q9JJL9 246 21 -

Motif 6 width=18
Element Seqn Id St Int Rpt
ARGGGRSREGTMELRTTP Q9NPC1 345 39 -
ARGGGRSREGTMELRTTP Q9NPE5 314 39 -
ARGGSRSREGTMELRTTP Q9JJL9 314 39 -

Motif 7 width=17
Element Seqn Id St Int Rpt
QLKVVGQGRGNGDPGGG Q9NPC1 363 0 -
QLKVVGQGRGNGDPGGG Q9NPE5 332 0 -
KLKVMGQGRGNGDPGGG Q9JJL9 332 0 -