WORKLIST ENTRIES (1):
PROTEASEAR4 View alignment View Structure Protease activated receptor 2 precursor signature
Type of fingerprint: COMPOUND with 11 elements
Links:
PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
PRINTS; PR00251 BACTRLOPSIN
PRINTS; PR01428 PROTEASEAR; PR01152 PROTEASEAR2; PR01429 PROTEASEAR3
Creation date 23-SEP-2000
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).
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 [1,2]. 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 FINGERPRINT INDEX
11| 2 2 2 2 2 2 2 2 2 2 2
10| 0 0 0 0 0 0 0 0 0 0 0
9| 0 0 0 0 0 0 0 0 0 0 0
8| 0 0 0 0 0 0 0 0 0 0 0
7| 0 0 0 0 0 0 0 0 0 0 0
6| 0 0 0 0 0 0 0 0 0 0 0
5| 0 0 0 0 0 0 0 0 0 0 0
4| 0 0 0 0 0 0 0 0 0 0 0
3| 0 0 0 0 0 0 0 0 0 0 0
2| 0 0 0 0 0 0 0 0 0 0 0
--+--------------------------------------------------------
| 1 2 3 4 5 6 7 8 9 10 11
True positives..
O76067 O88634
PROTEIN 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 MOTIF SETS
PROTEASEAR41 Length of motif = 12 Motif number = 1
Protease activated receptor 4 motif I - 1
PCODE ST INT
LLWPLVLGFSLS O76067 6 6
LLYPLVLGLSIS O88634 5 5
PROTEASEAR42 Length of motif = 16 Motif number = 2
Protease activated receptor 4 motif II - 1
PCODE ST INT
GTQTPSVYDESGSTGG O76067 19 1
GIQTPSIYDDVESTRG O88634 20 3
PROTEASEAR43 Length of motif = 19 Motif number = 3
Protease activated receptor 4 motif III - 1
PCODE ST INT
SILPAPRGYPGQVCANDSD O76067 41 6
SDKPNPRGYPGKFCANDSD O88634 53 17
PROTEASEAR44 Length of motif = 20 Motif number = 4
Protease activated receptor 4 motif IV - 1
PCODE ST INT
DTLELPDSSRALLLGWVPTR O76067 59 -1
DTLELPASSQALLLGWVSTR O88634 71 -1
PROTEASEAR45 Length of motif = 15 Motif number = 5
Protease activated receptor 4 motif V - 1
PCODE ST INT
VLATQAPRLPSTMLL O76067 101 22
VLATRVPRLPSTILL O88634 113 22
PROTEASEAR46 Length of motif = 19 Motif number = 6
Protease activated receptor 4 motif VI - 1
PCODE ST INT
ATAALYGHMYGSVLLLAAV O76067 152 36
ATAALYGHMYGSVLLLAAV O88634 164 36
PROTEASEAR47 Length of motif = 17 Motif number = 7
Protease activated receptor 4 motif VII - 1
PCODE ST INT
LTLQRQTFRLARSDRVL O76067 211 40
LTLHRQTFRLAGSDRML O88634 223 40
PROTEASEAR48 Length of motif = 21 Motif number = 8
Protease activated receptor 4 motif VIII - 1
PCODE ST INT
LDAQASHWQPAFTCLALLGCF O76067 234 6
LTEQTSHWRPAFICLAVLGCF O88634 246 6
PROTEASEAR49 Length of motif = 15 Motif number = 9
Protease activated receptor 4 motif IX - 1
PCODE ST INT
LAASGRRYGHALRLT O76067 271 16
LAANGQRYSHALRLT O88634 283 16
PROTEASEAR410 Length of motif = 16 Motif number = 10
Protease activated receptor 4 motif X - 1
PCODE ST INT
PSPSAWGNLYGAYVPS O76067 310 24
PSPEAWGNLYGAYVPS O88634 322 24
PROTEASEAR411 Length of motif = 23 Motif number = 11
Protease activated receptor 4 motif XI - 1
PCODE ST INT
PGDTVASKASAEGGSRGMGTHSS O76067 360 34
PEASSSSQASREAGSRGTAICSS O88634 371 33
FINAL MOTIF SETS
PROTEASEAR41 Length of motif = 12 Motif number = 1
Protease activated receptor 4 motif I - 1
PCODE ST INT
LLWPLVLGFSLS O76067 6 6
LLYPLVLGLSIS O88634 5 5
PROTEASEAR42 Length of motif = 16 Motif number = 2
Protease activated receptor 4 motif II - 1
PCODE ST INT
GTQTPSVYDESGSTGG O76067 19 1
GIQTPSIYDDVESTRG O88634 20 3
PROTEASEAR43 Length of motif = 19 Motif number = 3
Protease activated receptor 4 motif III - 1
PCODE ST INT
SILPAPRGYPGQVCANDSD O76067 41 6
SDKPNPRGYPGKFCANDSD O88634 53 17
PROTEASEAR44 Length of motif = 20 Motif number = 4
Protease activated receptor 4 motif IV - 1
PCODE ST INT
DTLELPDSSRALLLGWVPTR O76067 59 -1
DTLELPASSQALLLGWVSTR O88634 71 -1
PROTEASEAR45 Length of motif = 15 Motif number = 5
Protease activated receptor 4 motif V - 1
PCODE ST INT
VLATQAPRLPSTMLL O76067 101 22
VLATRVPRLPSTILL O88634 113 22
PROTEASEAR46 Length of motif = 19 Motif number = 6
Protease activated receptor 4 motif VI - 1
PCODE ST INT
ATAALYGHMYGSVLLLAAV O76067 152 36
ATAALYGHMYGSVLLLAAV O88634 164 36
PROTEASEAR47 Length of motif = 17 Motif number = 7
Protease activated receptor 4 motif VII - 1
PCODE ST INT
LTLQRQTFRLARSDRVL O76067 211 40
LTLHRQTFRLAGSDRML O88634 223 40
PROTEASEAR48 Length of motif = 21 Motif number = 8
Protease activated receptor 4 motif VIII - 1
PCODE ST INT
LDAQASHWQPAFTCLALLGCF O76067 234 6
LTEQTSHWRPAFICLAVLGCF O88634 246 6
PROTEASEAR49 Length of motif = 15 Motif number = 9
Protease activated receptor 4 motif IX - 1
PCODE ST INT
LAASGRRYGHALRLT O76067 271 16
LAANGQRYSHALRLT O88634 283 16
PROTEASEAR410 Length of motif = 16 Motif number = 10
Protease activated receptor 4 motif X - 1
PCODE ST INT
PSPSAWGNLYGAYVPS O76067 310 24
PSPEAWGNLYGAYVPS O88634 322 24
PROTEASEAR411 Length of motif = 23 Motif number = 11
Protease activated receptor 4 motif XI - 1
PCODE ST INT
PGDTVASKASAEGGSRGMGTHSS O76067 360 34
PEASSSSQASREAGSRGTAICSS O88634 371 33
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