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PR00908

Identifier
THROMBINR  [View Relations]  [View Alignment]  
Accession
PR00908
No. of Motifs
8
Creation Date
07-JUN-1998  (UPDATE 07-JUN-1999)
Title
Thrombin receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01428 PROTEASEAR
INTERPRO; IPR000935
GCRDB; GCR_0166; GCR_0432; GCR_0603; GCR_0263; GCR_0088
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. WATSON, S. AND ARKINSTALL,
Thrombin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp272-274.

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 serine protease with a central role in blood clotting [6].
It cleaves various substrates involved in coagulation, and activates cell
surface receptors via a novel proteolytic action. Thrombin stimulates
aggregation and secretion in blood platelets at the site of vascular injury,
and also has inflammatory and reparative actions, stimulating chemotaxis in
monocytes, proliferation of fibroblasts and lymphocytes, and inducing
endothelium-dependent relaxation of blood vessels [6]. The protein activates
a number of substrates involved in coagulation: it cleaves fibrinogen to
fibrin and activates coagulation factor XIII; it also activates factors V
and VIII [6]. When bound to thrombomodulin, it activates plasma protein C, 
which, in concert with protein S, inactivates factors Va and VIIIa, leading
to a decrease in thrombin formation [6].
 
The thrombin receptor is expressed in high levels in platelets, vascular
endothelial cells, and various cell lines [6]. The receptor activates 
phosphoinositide metabolism via a pertussis-toxin-insensitive G protein,
and inhibits adenylyl cyclase via a pertussis-toxin-sensitive G protein [6].
 
THROMBINR is an 8-element fingerprint that provides a signature for
thrombin receptors. The fingerprint was derived from an initial alignment
of 8 sequences: the motifs were drawn from conserved sections spanning
the full alignment length, focusing on those regions that characterise
the thrombin receptors but distinguish them from the rest of the
rhodopsin-like GPCRs - motifs 1 and 2 lie at the N-terminus; motif 3 spans
the first cytoplasmic loop; motif 4 spans the second cytoplasmic loop; motif
5 lies in the second external loop, leading into TM domain 6; motif 6 spans 
the third cytoplasmic loop; and motifs 7 and 8 lie at the C-terminus. A 
single iteration on OWL30.2 was required to reach convergence, no further
sequences being identified beyond the starting set.
 
An update on SPTR37_9f identified a true set of 6 sequences.
Summary Information
6 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
866666666
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
THRR_CRILO    THRR_HUMAN    THRR_MOUSE    THRR_PAPHA    
THRR_RAT THRR_XENLA
Sequence Titles
THRR_CRILO  THROMBIN RECEPTOR PRECURSOR - CRICETULUS LONGICAUDATUS (LONG-TAILED HAMSTER) (CHINESE HAMSTER). 
THRR_HUMAN THROMBIN RECEPTOR PRECURSOR - HOMO SAPIENS (HUMAN).
THRR_MOUSE THROMBIN RECEPTOR PRECURSOR - MUS MUSCULUS (MOUSE).
THRR_PAPHA THROMBIN RECEPTOR PRECURSOR - PAPIO HAMADRYAS (HAMADRYAS BABOON).
THRR_RAT THROMBIN RECEPTOR PRECURSOR - RATTUS NORVEGICUS (RAT).
THRR_XENLA THROMBIN RECEPTOR PRECURSOR - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
Scan History
OWL30_2    1  100  NSINGLE    
SPTR37_9f 2 7 NSINGLE
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
RLLLVAVGLSLCGPLLS THRR_RAT 5 5 -
RLLIVALGLSLCGPLLS THRR_MOUSE 5 5 -
RLLLVAAGLSLCGPLLS THRR_CRILO 5 5 -
RLLIVALGLSLCGPLLS MUSTHRRCT 5 5 -
RLLLVAACLCLCGPLLS AF028727 5 5 -
RLLLVAAGLSLCGPLLS CLTHRREC 5 5 -
RVLLLLLLLTLLGAMGS THRR_XENLA 5 5 -
RLLLVAACFSLCGPLLS THRR_HUMAN 5 5 -

Motif 2 width=17
Element Seqn Id St Int Rpt
ISEDASGYLTSPWLRLF THRR_CRILO 91 69 -
ITKEAEQYLSSQWLTKF THRR_XENLA 87 65 -
ISEDASGYLTSPWLTLF THRR_RAT 95 73 -
ISEDASGYLTSPWLRLF CLTHRREC 90 68 -
ISEDASGYLTSPWLTLF MUSTHRRCT 93 71 -
ISEDASGYLTSSWLTLF AF028727 88 66 -
ISEDASGYLTSSWLTLF THRR_HUMAN 88 66 -
ISEDASGYLTSPWLTLF THRR_MOUSE 93 71 -

Motif 3 width=14
Element Seqn Id St Int Rpt
KMKVKKPAVVYMLH AF028727 130 25 -
KMKVKKPAVVYMLH CLTHRREC 132 25 -
RMKVKKPAVVYMLH MUSTHRRCT 135 25 -
KMKVKKPAVVYMLH THRR_CRILO 133 25 -
RMKVKKPAVVYMLH THRR_MOUSE 135 25 -
KMKVKKPAVVYMLH THRR_HUMAN 130 25 -
RMKVKKPAVVYMLH THRR_RAT 137 25 -
KMKVRKPAVVYMLN THRR_XENLA 129 25 -

Motif 4 width=15
Element Seqn Id St Int Rpt
QSLSWRTLGGANFTC MUSTHRRCT 214 65 -
QSLSWRTLGRANFTC CLTHRREC 211 65 -
QSLSWRTLGRANFTC THRR_MOUSE 214 65 -
QSLSWRTLGRANFTC THRR_CRILO 212 65 -
HSLSWRTMSRAYMAC THRR_XENLA 208 65 -
QSLSWRTLGRANFTC THRR_RAT 216 65 -
QSLSWRTLGRASFTC THRR_HUMAN 209 65 -
QSLSWRTLGRASFTC AF028727 209 65 -

Motif 5 width=14
Element Seqn Id St Int Rpt
FYIYYFSSFCLLFF THRR_XENLA 265 42 -
YYAYYFSAFSAVFF AF028727 266 42 -
FYSYYFSAFSAIFF MUSTHRRCT 271 42 -
FYSYYFSAFSAVFF CLTHRREC 268 42 -
FYSYYFSAFSAVFF THRR_CRILO 269 42 -
FYSYYFSAFSAIFF THRR_MOUSE 271 42 -
YYAYYFSAFSAVFF THRR_HUMAN 266 42 -
FYSYYFSAFSAIFF THRR_RAT 273 42 -

Motif 6 width=19
Element Seqn Id St Int Rpt
RSLSSSSIENSCKKTRALF THRR_XENLA 294 15 -
RCLSSSSVANRSKKSRALF CLTHRREC 297 15 -
RCLSSSAVANRSKKSRALF MUSTHRRCT 300 15 -
RCLSSSTVANRSKKSRALF AF028727 295 15 -
RCLSSSAVANRSKKSRALF THRR_HUMAN 295 15 -
RCLSSSAVANRSKKSRALF THRR_MOUSE 300 15 -
RCLSSSSVANRSKKSRALF THRR_CRILO 298 15 -
RCLSSSAVANRSKKSRALF THRR_RAT 302 15 -

Motif 7 width=19
Element Seqn Id St Int Rpt
CQRTLYGILCCKESSDPNS CLTHRREC 380 64 -
CQRHLYGILCCKESSDPNS THRR_CRILO 381 64 -
CQRHLYSILCCKESSDPNS THRR_MOUSE 383 64 -
CQRYVYSILCCKESSDPSS THRR_HUMAN 378 64 -
CQKHLYSILCCRESSDSNS THRR_RAT 385 64 -
CQRYLYSLLCCRKVSEPGS THRR_XENLA 373 60 -
CQRHLYSILCCKESSDPNS MUSTHRRCT 383 64 -
CQRYVYSILCCKESSDPSS AF028727 378 64 -

Motif 8 width=18
Element Seqn Id St Int Rpt
KMDTCSSHLNNSIYKKLL MUSTHRRCT 412 10 -
KNDNCSTNAKSSIYKKLL THRR_XENLA 402 10 -
KMDTCSSHLNNSIYKKLL THRR_RAT 414 10 -
KMDTCSSNLNNSIYKKLL THRR_HUMAN 407 10 -
KMDTCSSHLNNSIYKKLL THRR_MOUSE 412 10 -
KMDTCSSHLNNSIYKKLL THRR_CRILO 410 10 -
KMDTCSSNLNNSIYKKLL AF028727 407 10 -
KMDTCSSHLNNSIYKKLL CLTHRREC 409 10 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
RLLLVAAGLSLCGPLLS THRR_CRILO 5 5 -
RLLIVALGLSLCGPLLS THRR_MOUSE 5 5 -
RLLLVAACFSLCGPLLS THRR_HUMAN 5 5 -
RLLLVAACLCLCGPLLS THRR_PAPHA 5 5 -
RLLLVAVGLSLCGPLLS THRR_RAT 5 5 -
RVLLLLLLLTLLGAMGS THRR_XENLA 5 5 -

Motif 2 width=17
Element Seqn Id St Int Rpt
ISEDASGYLTSPWLRLF THRR_CRILO 91 69 -
ISEDASGYLTSPWLTLF THRR_MOUSE 93 71 -
ISEDASGYLTSSWLTLF THRR_HUMAN 88 66 -
ISEDASGYLTSSWLTLF THRR_PAPHA 88 66 -
ISEDASGYLTSPWLTLF THRR_RAT 95 73 -
ITKEAEQYLSSQWLTKF THRR_XENLA 87 65 -

Motif 3 width=14
Element Seqn Id St Int Rpt
KMKVKKPAVVYMLH THRR_CRILO 133 25 -
RMKVKKPAVVYMLH THRR_MOUSE 135 25 -
KMKVKKPAVVYMLH THRR_HUMAN 130 25 -
KMKVKKPAVVYMLH THRR_PAPHA 130 25 -
RMKVKKPAVVYMLH THRR_RAT 137 25 -
KMKVRKPAVVYMLN THRR_XENLA 129 25 -

Motif 4 width=15
Element Seqn Id St Int Rpt
QSLSWRTLGRANFTC THRR_CRILO 212 65 -
QSLSWRTLGRANFTC THRR_MOUSE 214 65 -
QSLSWRTLGRASFTC THRR_HUMAN 209 65 -
QSLSWRTLGRASFTC THRR_PAPHA 209 65 -
QSLSWRTLGRANFTC THRR_RAT 216 65 -
HSLSWRTMSRAYMAC THRR_XENLA 208 65 -

Motif 5 width=14
Element Seqn Id St Int Rpt
FYSYYFSAFSAVFF THRR_CRILO 269 42 -
FYSYYFSAFSAIFF THRR_MOUSE 271 42 -
YYAYYFSAFSAVFF THRR_HUMAN 266 42 -
YYAYYFSAFSAVFF THRR_PAPHA 266 42 -
FYSYYFSAFSAIFF THRR_RAT 273 42 -
FYIYYFSSFCLLFF THRR_XENLA 265 42 -

Motif 6 width=19
Element Seqn Id St Int Rpt
RCLSSSSVANRSKKSRALF THRR_CRILO 298 15 -
RCLSSSAVANRSKKSRALF THRR_MOUSE 300 15 -
RCLSSSAVANRSKKSRALF THRR_HUMAN 295 15 -
RCLSSSTVANRSKKSRALF THRR_PAPHA 295 15 -
RCLSSSAVANRSKKSRALF THRR_RAT 302 15 -
RSLSSSSIENSCKKTRALF THRR_XENLA 294 15 -

Motif 7 width=19
Element Seqn Id St Int Rpt
CQRHLYGILCCKESSDPNS THRR_CRILO 381 64 -
CQRHLYSILCCKESSDPNS THRR_MOUSE 383 64 -
CQRYVYSILCCKESSDPSS THRR_HUMAN 378 64 -
CQRYVYSILCCKESSDPSS THRR_PAPHA 378 64 -
CQKHLYSILCCRESSDSNS THRR_RAT 385 64 -
CQRYLYSLLCCRKVSEPGS THRR_XENLA 373 60 -

Motif 8 width=18
Element Seqn Id St Int Rpt
KMDTCSSHLNNSIYKKLL THRR_CRILO 410 10 -
KMDTCSSHLNNSIYKKLL THRR_MOUSE 412 10 -
KMDTCSSNLNNSIYKKLL THRR_HUMAN 407 10 -
KMDTCSSNLNNSIYKKLL THRR_PAPHA 407 10 -
KMDTCSSHLNNSIYKKLL THRR_RAT 414 10 -
KNDNCSTNAKSSIYKKLL THRR_XENLA 402 10 -