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PR01428

Identifier
PROTEASEAR  [View Relations]  [View Alignment]  
Accession
PR01428
No. of Motifs
5
Creation Date
23-SEP-2000
Title
Protease activated receptor precursor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01152 PROTEASEAR2; PR01429 PROTEASEAR3; PR01430 PROTEASEAR4
PRINTS; PR00908 THROMBINR
GCRDB; GCR_1727; GCR_1964; 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].
 
PROTEASEAR is a 5-element fingerprint that provides a signature for
protease activated receptors. The fingerprint was derived from an initial
alignment of 7 sequences: the motifs were drawn from short conserved regions
spanning the full alignment length, focusing on those sections that 
characterise the protease activated receptors but distinguish them from 
the rest of the rhodopsin-like superfamily - motif 1 spans the N-terminal
portion of TM domain 1; motif 2 lies within the first extracellular loop;
motifs 3 and 4 encode the N-terminal portions of TM domains 5 and 6
respectively; and motif 5 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. Three partial matches were found: 
GPRH_HUMAN and O95853 are putative GPCR from Homo sapiens that match motifs 
2 and 4; and THRR_PAPHA is thrombin receptor precursor from Papio hamadryas
that matches motifs 1 and 2.
Summary Information
   7 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
3 codes involving 2 elements
Composite Feature Index
577777
400000
300000
213020
12345
True Positives
O76067        O88634        PAR2_HUMAN    PAR2_MOUSE    
PAR2_RAT PAR3_HUMAN PAR3_MOUSE
True Positive Partials
Codes involving 2 elements
GPRH_HUMAN O95853 THRR_PAPHA
Sequence Titles
O76067      PROTEASE-ACTIVATED RECEPTOR 4 - HOMO SAPIENS (HUMAN). 
O88634 PROTEASE-ACTIVATED RECEPTOR 4 - MUS MUSCULUS (MOUSE).
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).
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).

GPRH_HUMAN Putative G protein-coupled receptor GPR17 (R12) - Homo sapiens (Human).
O95853 ORPHAN G PROTEIN-COUPLED RECEPTOR - HOMO SAPIENS (HUMAN).
THRR_PAPHA THROMBIN RECEPTOR PRECURSOR - PAPIO HAMADRYAS (HAMADRYAS BABOON).
Scan History
SPTR37_10f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
SASILTGKLTTVFLPVVY PAR2_MOUSE 67 67 -
SASVLTGKLTTVFLPIVY PAR2_HUMAN 65 65 -
SASVLTGKLTTVFLPVIY PAR2_RAT 65 65 -
TMGYLTSSLSTKLIPAIY PAR3_HUMAN 84 84 -
TIGYLRSSLSTQVIPAIY PAR3_MOUSE 83 83 -
SQALLLGWVSTRLVPALY O88634 79 79 -
SRALLLGWVPTRLVPALY O76067 67 67 -

Motif 2 width=15
Element Seqn Id St Int Rpt
SYHLHGNNWVYGEAL PAR2_MOUSE 135 50 -
AYHIHGNNWIYGEAL PAR2_HUMAN 133 50 -
SYHLHGNDWTYGDAL PAR2_RAT 133 50 -
AYHLNGNNWVFGEVL PAR3_HUMAN 151 49 -
AYHLNGNNWVFGEVM PAR3_MOUSE 150 49 -
AYHLRGQRWPFGEAA O88634 146 49 -
AYHLRGQRWPFGEAA O76067 134 49 -

Motif 3 width=12
Element Seqn Id St Int Rpt
FLSLAIGVFLFP PAR2_MOUSE 245 95 -
FLSLAIGVFLFP PAR2_HUMAN 243 95 -
FLSLAIGVFLFP PAR2_RAT 243 95 -
FISLAFFGFLIP PAR3_HUMAN 263 97 -
FVSLAFFGFLIP PAR3_MOUSE 262 97 -
FICLAVLGCFVP O88634 257 96 -
FTCLALLGCFLP O76067 245 96 -

Motif 4 width=14
Element Seqn Id St Int Rpt
RLIITVLAMYFICF PAR2_MOUSE 289 32 -
KLIVTVLAMYLICF PAR2_HUMAN 287 32 -
RLIITVLSMYFICF PAR2_RAT 287 32 -
KASLLILVIFTICF PAR3_HUMAN 301 26 -
KAVLLILVIFTICF PAR3_MOUSE 300 26 -
RLTALVLFSAVASF O88634 295 26 -
RLTAVVLASAVAFF O76067 283 26 -

Motif 5 width=14
Element Seqn Id St Int Rpt
HYFLIKTQRQSHVY PAR2_MOUSE 312 9 -
HYFLIKSQGQSHVY PAR2_HUMAN 310 9 -
HYFLIKSQRQSHVY PAR2_RAT 310 9 -
HHANYYYNNTDGLY PAR3_HUMAN 324 9 -
HHANYYYHNTDSLY PAR3_MOUSE 323 9 -
HYSNPSPEAWGNLY O88634 318 9 -
HYSDPSPSAWGNLY O76067 306 9 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
SASILTGKLTTVFLPVVY PAR2_MOUSE 67 67 -
SASVLTGKLTTVFLPIVY PAR2_HUMAN 65 65 -
SASVLTGKLTTVFLPVIY PAR2_RAT 65 65 -
TMGYLTSSLSTKLIPAIY PAR3_HUMAN 84 84 -
TIGYLRSSLSTQVIPAIY PAR3_MOUSE 83 83 -
SQALLLGWVSTRLVPALY O88634 79 79 -
SRALLLGWVPTRLVPALY O76067 67 67 -

Motif 2 width=15
Element Seqn Id St Int Rpt
SYHLHGNNWVYGEAL PAR2_MOUSE 135 50 -
AYHIHGNNWIYGEAL PAR2_HUMAN 133 50 -
SYHLHGNDWTYGDAL PAR2_RAT 133 50 -
AYHLNGNNWVFGEVL PAR3_HUMAN 151 49 -
AYHLNGNNWVFGEVM PAR3_MOUSE 150 49 -
AYHLRGQRWPFGEAA O88634 146 49 -
AYHLRGQRWPFGEAA O76067 134 49 -

Motif 3 width=12
Element Seqn Id St Int Rpt
FLSLAIGVFLFP PAR2_MOUSE 245 95 -
FLSLAIGVFLFP PAR2_HUMAN 243 95 -
FLSLAIGVFLFP PAR2_RAT 243 95 -
FISLAFFGFLIP PAR3_HUMAN 263 97 -
FVSLAFFGFLIP PAR3_MOUSE 262 97 -
FICLAVLGCFVP O88634 257 96 -
FTCLALLGCFLP O76067 245 96 -

Motif 4 width=14
Element Seqn Id St Int Rpt
RLIITVLAMYFICF PAR2_MOUSE 289 32 -
KLIVTVLAMYLICF PAR2_HUMAN 287 32 -
RLIITVLSMYFICF PAR2_RAT 287 32 -
KASLLILVIFTICF PAR3_HUMAN 301 26 -
KAVLLILVIFTICF PAR3_MOUSE 300 26 -
RLTALVLFSAVASF O88634 295 26 -
RLTAVVLASAVAFF O76067 283 26 -

Motif 5 width=14
Element Seqn Id St Int Rpt
HYFLIKTQRQSHVY PAR2_MOUSE 312 9 -
HYFLIKSQGQSHVY PAR2_HUMAN 310 9 -
HYFLIKSQRQSHVY PAR2_RAT 310 9 -
HHANYYYNNTDGLY PAR3_HUMAN 324 9 -
HHANYYYHNTDSLY PAR3_MOUSE 323 9 -
HYSNPSPEAWGNLY O88634 318 9 -
HYSDPSPSAWGNLY O76067 306 9 -