SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR01429

Identifier
PROTEASEAR3  [View Relations]  [View Alignment]  
Accession
PR01429
No. of Motifs
10
Creation Date
23-SEP-2000
Title
Protease activated receptor 3 precursor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01428 PROTEASEAR
GCRDB; GCR_1320; GCR_1298
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. ISHIHARA, H., CONNOLLY, A.J., ZENG, D., KAHN, M.L., ZHENG, Y.W.,
TIMMONS, C., TRAM T. AND  COUGHLIN, S.R. 
Protease-activated receptor 3 is a second thrombin receptor in humans
NATURE 386 502-506 (1997).
 
7.NYSTEDT, S., LARSSON, A.K., ABERG, H. AND SUNDELIN, J.
The mouse proteinase-activated receptor-2 cDNA and gene. Molecular cloning
and functional expression.
J.BIOL.CHEM. 270 5950-5955 (1995).   
 
8. KAHN, M., ISHII, K., KUO, W.L., PIPER, M., CONNOLLY, A., SHI, Y.P.,
WU, R., LIN, C.C. AND COUGHLIN, S.R.
Conserved structure and adjacent location of the thrombin receptor and
protease-activated receptor 2 genes define a protease-activated receptor 
gene cluster
MOL.MED. 2 349-357 (1996). 

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]. 
 
Thrombin is a coagulation protease that activates platelets, leukocytes, 
endothelial and mesenchymal cells at sites of vascular injury, acting partly
through an unusual proteolytically activated GPCR [6]. Gene knockout 
experiments have provided definitive evidence for a second thrombin receptor
in mouse platelets and have suggested tissue-specific roles for different
thrombin receptors. Because the physiological agonist at the receptor was
originally unknown, it was provisionally named protease-activated receptor
(PAR) [7]. At least 4 PAR subtypes have now been characterised. Thus, the 
thrombin and PAR receptors constitute a fledgling receptor family that 
shares a novel proteolytic activation mechanism [8].
 
The human thrombin receptor, designated protease-activated receptor 3 (PAR3),
has been cloned and characterised [6]. PAR3 can mediate thrombin-triggered
phosphoinositide hydrolysis and is expressed in a variety of tissues, 
including human bone marrow and mouse megakaryocytes, making it a candidate
for the sought-after second platelet thrombin receptor [6]. PAR3 provides a
new tool for understanding thrombin signalling and a possible target for
therapeutics designed selectively to block thrombotic, inflammatory and
proliferative responses to thrombin [6].  
 
PROTEASEAR3 is a 10-element fingerprint that provides a signature for
protease activated receptor 3. The fingerprint was derived from an initial
alignment of 2 sequences: the motifs were drawn from short conserved regions
spanning the full alignment length, focusing on those sections that 
characterise the PAR 3 receptor but distinguish it from closely related 
members of the PAR family - motifs 1-4 reside at the N-terminus; motif 5
spans the first cytoplasmic loop, leading into TM domain 2; motif 6 resides
in the second cytoplasmic loop; motifs 7 and 8 span the second external loop;
motif 9 encodes part of the third cytoplasmic loop, leading into TM domain 6;
and motif 10 spans the third external loop. A single iteration on SPTR37_10f
was required to reach convergence, no further sequences being identified 
beyond the starting set.
Summary Information
2 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 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
102222222222
90000000000
80000000000
70000000000
60000000000
50000000000
40000000000
30000000000
20000000000
12345678910
True Positives
PAR3_HUMAN    PAR3_MOUSE    
Sequence Titles
PAR3_HUMAN  Proteinase-activated receptor 3 precursor (PAR-3) (Thrombin receptor- like 2) (Coagulation factor II receptor-like 2) - Homo sapiens (Human). 
PAR3_MOUSE Proteinase-activated receptor 3 precursor (PAR-3) (Thrombin receptor- like 2) (Coagulation factor II receptor-like 2) - Mus musculus (Mouse).
Scan History
SPTR37_10f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
KALIFAAAGLLLLLPTFCQSG PAR3_HUMAN 2 2 -
KILILVAAGLLFLPVTVCQSG PAR3_MOUSE 2 2 -

Motif 2 width=22
Element Seqn Id St Int Rpt
AKPTLPIKTFRGAPPNSFEEFP PAR3_HUMAN 31 8 -
AKPTLTIKSFNGGPQNTFEEFP PAR3_MOUSE 30 7 -

Motif 3 width=18
Element Seqn Id St Int Rpt
EGWTGATITVKIKCPEES PAR3_HUMAN 57 4 -
EGWTGATTTIKAECPEDS PAR3_MOUSE 56 4 -

Motif 4 width=17
Element Seqn Id St Int Rpt
LHVKNATMGYLTSSLST PAR3_HUMAN 78 3 -
LHVNNATIGYLRSSLST PAR3_MOUSE 77 3 -

Motif 5 width=15
Element Seqn Id St Int Rpt
LFFRTRSICTTVFYT PAR3_HUMAN 119 24 -
LSLRTKSISLVIFHT PAR3_MOUSE 118 24 -

Motif 6 width=18
Element Seqn Id St Int Rpt
PFTYRGLPKHTYALVTCG PAR3_HUMAN 198 64 -
PFTYQKLPKRSFSLLMCG PAR3_MOUSE 197 64 -

Motif 7 width=12
Element Seqn Id St Int Rpt
QEYYLVQPDITT PAR3_HUMAN 233 17 -
QEYHLVHSEITT PAR3_MOUSE 232 17 -

Motif 8 width=12
Element Seqn Id St Int Rpt
CESSSPFQLYYF PAR3_HUMAN 252 7 -
CESPSSFRFYYF PAR3_MOUSE 251 7 -

Motif 9 width=13
Element Seqn Id St Int Rpt
DHRWLWYVKASLL PAR3_HUMAN 293 29 -
DRIWLGYIKAVLL PAR3_MOUSE 292 29 -

Motif 10 width=16
Element Seqn Id St Int Rpt
IHHANYYYNNTDGLYF PAR3_HUMAN 323 17 -
IHHANYYYHNTDSLYF PAR3_MOUSE 322 17 -
Final Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
KALIFAAAGLLLLLPTFCQSG PAR3_HUMAN 2 2 -
KILILVAAGLLFLPVTVCQSG PAR3_MOUSE 2 2 -

Motif 2 width=22
Element Seqn Id St Int Rpt
AKPTLPIKTFRGAPPNSFEEFP PAR3_HUMAN 31 8 -
AKPTLTIKSFNGGPQNTFEEFP PAR3_MOUSE 30 7 -

Motif 3 width=18
Element Seqn Id St Int Rpt
EGWTGATITVKIKCPEES PAR3_HUMAN 57 4 -
EGWTGATTTIKAECPEDS PAR3_MOUSE 56 4 -

Motif 4 width=17
Element Seqn Id St Int Rpt
LHVKNATMGYLTSSLST PAR3_HUMAN 78 3 -
LHVNNATIGYLRSSLST PAR3_MOUSE 77 3 -

Motif 5 width=15
Element Seqn Id St Int Rpt
LFFRTRSICTTVFYT PAR3_HUMAN 119 24 -
LSLRTKSISLVIFHT PAR3_MOUSE 118 24 -

Motif 6 width=18
Element Seqn Id St Int Rpt
PFTYRGLPKHTYALVTCG PAR3_HUMAN 198 64 -
PFTYQKLPKRSFSLLMCG PAR3_MOUSE 197 64 -

Motif 7 width=12
Element Seqn Id St Int Rpt
QEYYLVQPDITT PAR3_HUMAN 233 17 -
QEYHLVHSEITT PAR3_MOUSE 232 17 -

Motif 8 width=12
Element Seqn Id St Int Rpt
CESSSPFQLYYF PAR3_HUMAN 252 7 -
CESPSSFRFYYF PAR3_MOUSE 251 7 -

Motif 9 width=13
Element Seqn Id St Int Rpt
DHRWLWYVKASLL PAR3_HUMAN 293 29 -
DRIWLGYIKAVLL PAR3_MOUSE 292 29 -

Motif 10 width=16
Element Seqn Id St Int Rpt
IHHANYYYNNTDGLYF PAR3_HUMAN 323 17 -
IHHANYYYHNTDSLYF PAR3_MOUSE 322 17 -