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PR01152

Identifier
PROTEASEAR2  [View Relations]  [View Alignment]  
Accession
PR01152
No. of Motifs
10
Creation Date
14-MAR-1999
Title
Protease activated receptor 2 precursor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01428 PROTEASEAR
INTERPRO; IPR002281
GCRDB; GCR_1964; GCR_1727
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. BOHM, S.K., KONG, W., BROMME, D., SMEEKENS, S.P., ANDERSON, D.C.,
CONNOLLY, A., KAHN, M., NELKEN, N.A., COUGHLIN, S.R., PAYAN, D.G.
AND BUNNETT, N.W.
Molecular cloning, expression and potential functions of the human
proteinase-activated receptor-2.
BIOCHEM.J. 314 1009-1016 (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].
 
Human PAR-2 (hPAR-2) resides both on the plasma membrane and in the Golgi 
apparatus [9]. hPAR-2 mRNA is highly expressed in human pancreas, kidney,
colon, liver and small intestine, and by A549 lung and SW480 colon 
adenocarcinoma cells [9]. Hybridisation in situ reveals high expression in 
intestinal epithelial cells throughout the gut [9], where it is thought that
PAR-2 may serve as a trypsin sensor [9]. Its expression by cells and tissues
not normally exposed to pancreatic trypsin suggests that other proteases
could serve as physiological activators [9]. 
 
PROTEASEAR2 is a 10-element fingerprint that provides a signature for
protease activated receptor 2. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from short conserved regions
spanning the full alignment length, focusing on those sections that 
characterise the PAR 2 receptor but distinguish it from closely related
members of the PAR family - motifs 1-3 reside at the N-terminus; motif 4
lies in the first external loop; motif 5 lies in the second cytoplasmic
loop, leading into TM domain 4; motif 6 lies in the second external loop,
leading into TM domain 5; motif 7 lies in the third cytoplasmic loop,
leading into TM domain 6; motif 8 lies in the third external loop, leading 
into TM domain 7; and motifs 9 and 10 reside at the C-terminus. A single
iteration on SPTR37_9f was required to reach convergence, no further
sequences being identified beyond the starting set.
Summary Information
3 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
103333333333
90000000000
80000000000
70000000000
60000000000
50000000000
40000000000
30000000000
20000000000
12345678910
True Positives
PAR2_HUMAN    PAR2_MOUSE    PAR2_RAT      
Sequence Titles
PAR2_HUMAN  Proteinase-activated receptor 2 precursor (PAR-2) (Thrombin receptor- like 1) (Coagulation factor II receptor-like 1) (G-protein coupled receptor 11) - Homo sapiens (Human). 
PAR2_MOUSE Proteinase-activated receptor 2 precursor (PAR-2) (Thrombin receptor- like 1) (Coagulation factor II receptor-like 1) (G-protein coupled receptor 11) - Mus musculus (Mouse).
PAR2_RAT Proteinase-activated receptor 2 precursor (PAR-2) (Thrombin receptor- like 1) (Coagulation factor II receptor-like 1) - Rattus norvegicus (Rat).
Scan History
SPTR37_9f  1  4    NSINGLE    
Initial Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
RSLSLAWLLGGITLLAASASCNRT PAR2_RAT 2 2 -
RSLSLAWLLGGITLLAASVSCSRT PAR2_MOUSE 2 2 -
RSPSAAWLLGAAILLAASLSCSGT PAR2_HUMAN 2 2 -

Motif 2 width=17
Element Seqn Id St Int Rpt
SKGRSLIGRLDTPPPIT PAR2_RAT 33 7 -
SKGRSLIGRLETQPPIT PAR2_MOUSE 35 9 -
SKGRSLIGKVDGTSHVT PAR2_HUMAN 33 7 -

Motif 3 width=24
Element Seqn Id St Int Rpt
TGKGAPVEPGFSVDEFSASVLTGK PAR2_RAT 49 -1 -
TGKGVPVEPGFSIDEFSASILTGK PAR2_MOUSE 51 -1 -
TGKGVTVETVFSVDEFSASVLTGK PAR2_HUMAN 49 -1 -

Motif 4 width=17
Element Seqn Id St Int Rpt
SVIWFPLKISYHLHGND PAR2_RAT 124 51 -
SVIWFPLKISYHLHGNN PAR2_MOUSE 126 51 -
SVIWFPLKIAYHIHGNN PAR2_HUMAN 124 51 -

Motif 5 width=21
Element Seqn Id St Int Rpt
WVIVNPMGHSRKRANIAVGVS PAR2_RAT 175 34 -
WVIVNPMGHPRKKANIAVGVS PAR2_MOUSE 177 34 -
WVIVNPMGHSRKKANIAIGIS PAR2_HUMAN 175 34 -

Motif 6 width=19
Element Seqn Id St Int Rpt
PEEVLVGDMFSYFLSLAIG PAR2_RAT 231 35 -
PEEVLVGDMFNYFLSLAIG PAR2_MOUSE 233 35 -
PEQLLVGDMFNYFLSLAIG PAR2_HUMAN 231 35 -

Motif 7 width=20
Element Seqn Id St Int Rpt
SAMDEHSEKKRRRAIRLIIT PAR2_RAT 272 22 -
SAMDEHSEKKRQRAIRLIIT PAR2_MOUSE 274 22 -
SAMDENSEKKRKRAIKLIVT PAR2_HUMAN 272 22 -

Motif 8 width=12
Element Seqn Id St Int Rpt
IKSQRQSHVYAL PAR2_RAT 314 22 -
IKTQRQSHVYAL PAR2_MOUSE 316 22 -
IKSQGQSHVYAL PAR2_HUMAN 314 22 -

Motif 9 width=22
Element Seqn Id St Int Rpt
FVSKDFRDQARNALLCRSVRTV PAR2_RAT 346 20 -
FVSKDFRDHARNALLCRSVRTV PAR2_MOUSE 348 20 -
FVSHDFRDHAKNALLCRSVRTV PAR2_HUMAN 346 20 -

Motif 10 width=19
Element Seqn Id St Int Rpt
MQISLTSNKFSRKSSSYSS PAR2_RAT 370 2 -
MQISLSSNKFSRKSGSYSS PAR2_MOUSE 372 2 -
MQVSLTSKKHSRKSSSYSS PAR2_HUMAN 370 2 -
Final Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
RSLSLAWLLGGITLLAASASCNRT PAR2_RAT 2 2 -
RSLSLAWLLGGITLLAASVSCSRT PAR2_MOUSE 2 2 -
RSPSAAWLLGAAILLAASLSCSGT PAR2_HUMAN 2 2 -

Motif 2 width=17
Element Seqn Id St Int Rpt
SKGRSLIGRLDTPPPIT PAR2_RAT 33 7 -
SKGRSLIGRLETQPPIT PAR2_MOUSE 35 9 -
SKGRSLIGKVDGTSHVT PAR2_HUMAN 33 7 -

Motif 3 width=24
Element Seqn Id St Int Rpt
TGKGAPVEPGFSVDEFSASVLTGK PAR2_RAT 49 -1 -
TGKGVPVEPGFSIDEFSASILTGK PAR2_MOUSE 51 -1 -
TGKGVTVETVFSVDEFSASVLTGK PAR2_HUMAN 49 -1 -

Motif 4 width=17
Element Seqn Id St Int Rpt
SVIWFPLKISYHLHGND PAR2_RAT 124 51 -
SVIWFPLKISYHLHGNN PAR2_MOUSE 126 51 -
SVIWFPLKIAYHIHGNN PAR2_HUMAN 124 51 -

Motif 5 width=21
Element Seqn Id St Int Rpt
WVIVNPMGHSRKRANIAVGVS PAR2_RAT 175 34 -
WVIVNPMGHPRKKANIAVGVS PAR2_MOUSE 177 34 -
WVIVNPMGHSRKKANIAIGIS PAR2_HUMAN 175 34 -

Motif 6 width=19
Element Seqn Id St Int Rpt
PEEVLVGDMFSYFLSLAIG PAR2_RAT 231 35 -
PEEVLVGDMFNYFLSLAIG PAR2_MOUSE 233 35 -
PEQLLVGDMFNYFLSLAIG PAR2_HUMAN 231 35 -

Motif 7 width=20
Element Seqn Id St Int Rpt
SAMDEHSEKKRRRAIRLIIT PAR2_RAT 272 22 -
SAMDEHSEKKRQRAIRLIIT PAR2_MOUSE 274 22 -
SAMDENSEKKRKRAIKLIVT PAR2_HUMAN 272 22 -

Motif 8 width=12
Element Seqn Id St Int Rpt
IKSQRQSHVYAL PAR2_RAT 314 22 -
IKTQRQSHVYAL PAR2_MOUSE 316 22 -
IKSQGQSHVYAL PAR2_HUMAN 314 22 -

Motif 9 width=22
Element Seqn Id St Int Rpt
FVSKDFRDQARNALLCRSVRTV PAR2_RAT 346 20 -
FVSKDFRDHARNALLCRSVRTV PAR2_MOUSE 348 20 -
FVSHDFRDHAKNALLCRSVRTV PAR2_HUMAN 346 20 -

Motif 10 width=19
Element Seqn Id St Int Rpt
MQISLTSNKFSRKSSSYSS PAR2_RAT 370 2 -
MQISLSSNKFSRKSGSYSS PAR2_MOUSE 372 2 -
MQVSLTSKKHSRKSSSYSS PAR2_HUMAN 370 2 -