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PR01430

Identifier
PROTEASEAR4  [View Relations]  [View Alignment]  
Accession
PR01430
No. of Motifs
11
Creation Date
23-SEP-2000
Title
Protease activated receptor 4 precursor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01428 PROTEASEAR
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). 
 
9. XU, W.F., ANDERSEN, H., WHITMORE, T.E., PRESNELL, S.R., YEE, D.P.,
CHING, A., GILBERT, T., DAVIE, E.W. AND FOSTER, D.C.
Cloning and characterization of human protease-activated receptor 4.
PROC.NATL.ACAD.SCI.U.S.A. 95 6642-6646 (1998). 

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 4 (PAR4),
has been cloned and characterised [9]. Northern blot analysis showed that
PAR4 mRNA was expressed in a number of tissues, high levels being present
in lung, pancreas, thyroid, testis and small intestine [9]. Using
fluorescence in situ hybridisation, the human PAR4 gene has been mapped
to chromosome 19p12 [6]. 
 
PROTEASEAR4 is an 11-element fingerprint that provides a signature for
protease activated receptor 4. 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 4 receptor but distinguish it from closely related
members of the PAR family - motifs 1-4 reside at the N-terminus; motif
5 encompasses the first cytoplasmic loop and part of the TM domains to its
N- and C-termini; motif 6 encodes the central portion of TM domain 3; motifs
7 and 8 span the second external loop, leading into TM domain 5; motif 9
spans the third cytoplasmic loop; motif 10 encodes part of the third 
external loop, leading into TM domain 7; and motif 11 resides at the 
C-terminus. 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 11 elements
0 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
1122222222222
1000000000000
900000000000
800000000000
700000000000
600000000000
500000000000
400000000000
300000000000
200000000000
1234567891011
True Positives
O76067        O88634        
Sequence Titles
O76067      PROTEASE-ACTIVATED RECEPTOR 4 - HOMO SAPIENS (HUMAN). 
O88634 PROTEASE-ACTIVATED RECEPTOR 4 - MUS MUSCULUS (MOUSE).
Scan History
SPTR37_10f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
LLWPLVLGFSLS O76067 6 6 -
LLYPLVLGLSIS O88634 5 5 -

Motif 2 width=16
Element Seqn Id St Int Rpt
GTQTPSVYDESGSTGG O76067 19 1 -
GIQTPSIYDDVESTRG O88634 20 3 -

Motif 3 width=19
Element Seqn Id St Int Rpt
SILPAPRGYPGQVCANDSD O76067 41 6 -
SDKPNPRGYPGKFCANDSD O88634 53 17 -

Motif 4 width=20
Element Seqn Id St Int Rpt
DTLELPDSSRALLLGWVPTR O76067 59 -1 -
DTLELPASSQALLLGWVSTR O88634 71 -1 -

Motif 5 width=15
Element Seqn Id St Int Rpt
VLATQAPRLPSTMLL O76067 101 22 -
VLATRVPRLPSTILL O88634 113 22 -

Motif 6 width=19
Element Seqn Id St Int Rpt
ATAALYGHMYGSVLLLAAV O76067 152 36 -
ATAALYGHMYGSVLLLAAV O88634 164 36 -

Motif 7 width=17
Element Seqn Id St Int Rpt
LTLQRQTFRLARSDRVL O76067 211 40 -
LTLHRQTFRLAGSDRML O88634 223 40 -

Motif 8 width=21
Element Seqn Id St Int Rpt
LDAQASHWQPAFTCLALLGCF O76067 234 6 -
LTEQTSHWRPAFICLAVLGCF O88634 246 6 -

Motif 9 width=15
Element Seqn Id St Int Rpt
LAASGRRYGHALRLT O76067 271 16 -
LAANGQRYSHALRLT O88634 283 16 -

Motif 10 width=16
Element Seqn Id St Int Rpt
PSPSAWGNLYGAYVPS O76067 310 24 -
PSPEAWGNLYGAYVPS O88634 322 24 -

Motif 11 width=23
Element Seqn Id St Int Rpt
PGDTVASKASAEGGSRGMGTHSS O76067 360 34 -
PEASSSSQASREAGSRGTAICSS O88634 371 33 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
LLWPLVLGFSLS O76067 6 6 -
LLYPLVLGLSIS O88634 5 5 -

Motif 2 width=16
Element Seqn Id St Int Rpt
GTQTPSVYDESGSTGG O76067 19 1 -
GIQTPSIYDDVESTRG O88634 20 3 -

Motif 3 width=19
Element Seqn Id St Int Rpt
SILPAPRGYPGQVCANDSD O76067 41 6 -
SDKPNPRGYPGKFCANDSD O88634 53 17 -

Motif 4 width=20
Element Seqn Id St Int Rpt
DTLELPDSSRALLLGWVPTR O76067 59 -1 -
DTLELPASSQALLLGWVSTR O88634 71 -1 -

Motif 5 width=15
Element Seqn Id St Int Rpt
VLATQAPRLPSTMLL O76067 101 22 -
VLATRVPRLPSTILL O88634 113 22 -

Motif 6 width=19
Element Seqn Id St Int Rpt
ATAALYGHMYGSVLLLAAV O76067 152 36 -
ATAALYGHMYGSVLLLAAV O88634 164 36 -

Motif 7 width=17
Element Seqn Id St Int Rpt
LTLQRQTFRLARSDRVL O76067 211 40 -
LTLHRQTFRLAGSDRML O88634 223 40 -

Motif 8 width=21
Element Seqn Id St Int Rpt
LDAQASHWQPAFTCLALLGCF O76067 234 6 -
LTEQTSHWRPAFICLAVLGCF O88634 246 6 -

Motif 9 width=15
Element Seqn Id St Int Rpt
LAASGRRYGHALRLT O76067 271 16 -
LAANGQRYSHALRLT O88634 283 16 -

Motif 10 width=16
Element Seqn Id St Int Rpt
PSPSAWGNLYGAYVPS O76067 310 24 -
PSPEAWGNLYGAYVPS O88634 322 24 -

Motif 11 width=23
Element Seqn Id St Int Rpt
PGDTVASKASAEGGSRGMGTHSS O76067 360 34 -
PEASSSSQASREAGSRGTAICSS O88634 371 33 -