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PR01477

Identifier
LTB1RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01477
No. of Motifs
6
Creation Date
14-MAR-2001
Title
Leukotriene B4 type 1 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. YOKOMIZO, T., MASUDA, K., KATO, K., TODA, A., IZUMI, T. AND SHIMIZU, T.
Leukotriene B4 receptor: cloning and intracellular signaling.
AM.J.RESPIR.CRIT.CARE MED. 161(2) S51-S55 (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 1 receptor (BLT1) has been cloned from human, mouse,
rat and guinea pig, and was found to be identical to a previously cloned
receptor, P2Y7 [7,9]. This receptor was originally thought to be a
purinoceptor but is now widely accepted to bind LTB4. BLT1 has also been
reported to act as a coreceptor for macrophage-tropic HIV1 strains [9]. BLT1
is expressed primarily in peripheral leukocytes and peritoneal macrophages,
with lower levels of expression detected in the spleen and thymus of humans
[9]. Activation of the receptor by LTB4 leads to the production of inositol
trisphosphate and an increase in intracellular calcium levels. This response
is sensitive to pertussis toxin in some cell types. The receptor also causes
chemotaxis and inhibition of forskolin-stimulated adenylyl cyclase activity 
in a pertussis toxin sensitive manner. It has been demonstrated that BLT1
can couple to Gi2 and G16 G proteins, depending on the cell type in which
it is expressed [7].
 
LTB1RECEPTOR is a 6-element fingerprint that provides a signature for the
leukotriene B4 type 1 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 1 receptors but
distinguish them from the rest of the leukotriene B4 receptor family - motif
1 spans the N-terminus; motif 2 encodes the first cytoplasmic loop; motif 3
encodes the third cytoplasmic loop; motif 4 spans part of TM domain 6,
leading into the third external loop; and motifs 5 and 6 reside within 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
O88855        P2Y7_HUMAN    Q9R0Q2        Q9WTK1        
Sequence Titles
O88855      LEUKOTRIENE B4 RECEPTOR - Mus musculus (Mouse). 
P2Y7_HUMAN P2Y PURINOCEPTOR 7 (P2Y7) (LEUKOTRIENE B4 RECEPTOR) (CHEMOATTRACTANT RECEPTOR-LIKE 1) - Homo sapiens (Human).
Q9R0Q2 LEUKOTRIENE B4 RECEPTOR - Rattus norvegicus (Rat).
Q9WTK1 LTB4 RECEPTOR - Cavia porcellus (Guinea pig).
Scan History
SPTR39_15f 2  200  NSINGLE    
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
NTTSTAATSSPGGMSLSL Q9R0Q2 4 4 -
NTTSPAAPSSPGGMSLSL O88855 4 4 -
NTTTRAASPSGSNTFIPL Q9WTK1 4 4 -

Motif 2 width=13
Element Seqn Id St Int Rpt
SILKRMQKRSVTA Q9R0Q2 44 22 -
SILKRMQKRTVTA O88855 44 22 -
SILKRMRKRSVTA Q9WTK1 44 22 -

Motif 3 width=17
Element Seqn Id St Int Rpt
GRRLQARRFRRSRRTGR Q9R0Q2 206 149 -
GRRLQARRFRRSRRTGR O88855 206 149 -
SRRLRVRRFHRRRRTGR Q9WTK1 207 150 -

Motif 4 width=16
Element Seqn Id St Int Rpt
NLVEAGRTLAGWDKNS Q9R0Q2 242 19 -
NLVEAGRTVAGWDKNS O88855 242 19 -
DLVEGSRVLAGTLDQS Q9WTK1 243 19 -

Motif 5 width=15
Element Seqn Id St Int Rpt
VSSTRRGGTLVQTPK Q9R0Q2 312 54 -
VSSTRRGGTLVQTPK O88855 312 54 -
AFSTRRGGTLAQTVK Q9WTK1 311 52 -

Motif 6 width=12
Element Seqn Id St Int Rpt
PTCPEPGPTDSF Q9R0Q2 329 2 -
PACPEPGPTDSF O88855 329 2 -
PMAPEPGASGSL Q9WTK1 328 2 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
NTTSTAATSSPGGMSLSL Q9R0Q2 4 4 -
NTTSPAAPSSPGGMSLSL O88855 4 4 -
NTTSSAAPPSLGVEFISL P2Y7_HUMAN 2 2 -
NTTTRAASPSGSNTFIPL Q9WTK1 4 4 -

Motif 2 width=13
Element Seqn Id St Int Rpt
SILKRMQKRSVTA Q9R0Q2 44 22 -
SILKRMQKRTVTA O88855 44 22 -
SILKRMQKRSVTA P2Y7_HUMAN 42 22 -
SILKRMRKRSVTA Q9WTK1 44 22 -

Motif 3 width=17
Element Seqn Id St Int Rpt
GRRLQARRFRRSRRTGR Q9R0Q2 206 149 -
GRRLQARRFRRSRRTGR O88855 206 149 -
GRRLQARRFRRSRRTGR P2Y7_HUMAN 205 150 -
SRRLRVRRFHRRRRTGR Q9WTK1 207 150 -

Motif 4 width=16
Element Seqn Id St Int Rpt
NLVEAGRTLAGWDKNS Q9R0Q2 242 19 -
NLVEAGRTVAGWDKNS O88855 242 19 -
NLAEAGRALAGQAAGL P2Y7_HUMAN 241 19 -
DLVEGSRVLAGTLDQS Q9WTK1 243 19 -

Motif 5 width=15
Element Seqn Id St Int Rpt
VSSTRRGGTLVQTPK Q9R0Q2 312 54 -
VSSTRRGGTLVQTPK O88855 312 54 -
ASSTRRGGSLGQTAR P2Y7_HUMAN 312 55 -
AFSTRRGGTLAQTVK Q9WTK1 311 52 -

Motif 6 width=12
Element Seqn Id St Int Rpt
PTCPEPGPTDSF Q9R0Q2 329 2 -
PACPEPGPTDSF O88855 329 2 -
PAALEPGPSESL P2Y7_HUMAN 329 2 -
PMAPEPGASGSL Q9WTK1 328 2 -