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PR01505

Identifier
PROTHROMBIN  [View Relations]  [View Alignment]  
Accession
PR01505
No. of Motifs
8
Creation Date
02-NOV-1999
Title
Prothrombin signature
Database References
PRINTS; PR00722 CHYMOTRYPSIN
PDB; 1THP; 1THR
SCOP; 1THP; 1THR
CATH; 1THP; 1THR
Literature References
1. BODE, W., MAYR, I., BAUMANN, U., HUBER, R., STONE, S.R. AND HOFSTEENGE, J.
The refined 1.9A crystal structure of human alpha-thrombin: interaction with
D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp
insertion segment. 
EMBO J. 8 3467-3475 (1989).
 
2. GUINTO, E.R., CACCIA, S., ROSE, T., FUETTERER, K., WAKSMAN, G. 
AND DI CERA, E.
Unexpected crucial role of residue 225 in serine proteases.
PROC.NATL.ACAD.SCI.U.S.A. 96 1852-1857 (1999).
 
3. BANFIELD, D.K. AND MACGILLIVRAY, R.T.
Partial characterization of vertebrate prothrombin cDNAs: amplification and
sequence analysis of the B chain of thrombin from nine different species.
PROC.NATL.ACAD.SCI.U.S.A. 89 2779-2783 (1992). 

Documentation
The amino acid sequence of prothrombin has a modular architecture, 
comprising a series of N-terminal gamma-carboxyglutamate residues,
activation peptides 1 and 2, thrombin light chains A and B, and two kringle 
domains. Modification of the glutamyl residues is necessary for calcium-
dependent interaction of the protein with a negatively charged phospholipid 
surface, which is essential for the conversion of prothrombin to thrombin.
 
Prothrombin activation at the membrane surface is mediated by factors Va
and Xa. Factor Xa removes the activation peptide and cleaves the remaining
part into light and heavy chains. Activation is slow because factor V 
itself has to be activated by the initial small amounts of thrombin.
 
Thrombin is a member of the trypsin family of S1 peptidases. It catalyses
the preferential cleavage of arginine-lysine bonds, converting fibrinogen 
to fibrin, and releasing fibrinopeptides A and B. Thrombin can itself cleave
the N-terminal fragment (fragment 1) of prothrombin, prior to its activation
by factor Xa. Its effects are mediated by the thrombin receptor.
 
The structure of the thrombin A-chain has been determined to 1.9A resolution
[1]. The A-chain, which is ordered only in its central part, is positioned
along the molecular surface opposite to the active site. The B-chain 
exhibits the characteristic fold of trypsin-like proteases [1,2].
 
The most conserved portions of the B chain are the active-site residues and
adjacent amino acids, the B loop, and the primary substrate-binding region
[3]. The regions of poorest conservation in the B chain correspond to 
surface loops, including putative thrombomodulin-binding sites and a 
hirudin-binding region. The extent of sequence similarity between species
and the conservation of many of the functional/structural motifs suggests
that, in addition to their role in blood coagulation, vertebrate thrombins
may play an important role in the general mechanisms of wound repair [3].
 
PROTHROMBIN is an 4-element fingerprint that provides a signature for 
prothrombin. The fingerprint was derived from an initial alignment of 4 
sequences: the motifs were drawn from conserved regions spanning the 
C-terminal two-thirds of the alignment - motif 1 encodes the C-terminal 
alpha-helix of the thrombin light chain (A); and motifs 2-4 span the 
thrombin heavy chain (B) - motif 2 encodes helices 2 and 3 and strands 6 and
7; motif 3 encodes strand 10; and motif 4 spans strand 15 and helices 6 and 
7. A single iteration on SPTR37_10f was required to reach convergence, no 
further sequences being identified beyond the starting set. A single partial
match was found, 
 
An update on SPTR57.15_40.15f identified a true set of 21 sequences, and two
partial matches (Q90504_EPTST and B3XZZ0_LAMJA), which are pacific hagfish
and Japanese lamprey thrombins that fail to match motif 1.
Summary Information
   5 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
1 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
855555555
700000000
600000000
501100111
400000000
300000000
200000000
12345678
True Positives
Q91001        THRB_BOVIN    THRB_HUMAN    THRB_MOUSE    
THRB_RAT
True Positive Partials
Codes involving 5 elements
Q90504
Sequence Titles
Q91001      THROMBIN - GALLUS GALLUS (CHICKEN).           
THRB_BOVIN PROTHROMBIN PRECURSOR (EC 3.4.21.5) - BOS TAURUS (BOVINE).
THRB_HUMAN PROTHROMBIN PRECURSOR (EC 3.4.21.5) (COAGULATION FACTOR II) - HOMO SAPIENS (HUMA
THRB_MOUSE PROTHROMBIN PRECURSOR (EC 3.4.21.5) - MUS MUSCULUS (MOUSE).
THRB_RAT PROTHROMBIN PRECURSOR (EC 3.4.21.5) - RATTUS NORVEGICUS (RAT).

Q90504 THROMBIN - EPTATRETUS STOUTII (PACIFIC HAGFISH).
Scan History
SPTR37_10f 1  40   NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
LPWNSLPAKTLSKYQDF THRB_MOUSE 237 237 -
LAWDSLPTKTLSKYQNF THRB_RAT 237 237 -
LAWASAQAKALSKHQDF THRB_HUMAN 235 235 -
LAWSSEQAKALSKDQDF THRB_BOVIN 236 236 -
LPWASEKAKALLQDKTI Q91001 229 229 -

Motif 2 width=22
Element Seqn Id St Int Rpt
NFCRNPDWDEEGAWCYVAGQPG THRB_MOUSE 262 8 -
NFCRNPDRDEEGAWCFVAQQPG THRB_RAT 262 8 -
NFCRNPDGDEEGVWCYVAGKPG THRB_HUMAN 260 8 -
NFCRNPDGDEEGAWCYVADQPG THRB_BOVIN 261 8 -
NYCRNPDADDEGVWCVIDEPPY Q91001 254 8 -

Motif 3 width=19
Element Seqn Id St Int Rpt
FEYCNLNYCEEAVGEENYD THRB_MOUSE 285 1 -
FEYCSLNYCDEAVGEENHD THRB_RAT 284 0 -
FGYCDLNYCEEAVEEETGD THRB_HUMAN 283 1 -
FEYCDLNYCEEPVDGDLGD THRB_BOVIN 284 1 -
FEYCDLHYCDSSLEDENEQ Q91001 276 0 -

Motif 4 width=22
Element Seqn Id St Int Rpt
DESIAGRTTDAEFHTFFNEKTF THRB_MOUSE 305 1 -
DESIAGRTTDAEFHTFFDERTF THRB_RAT 304 1 -
DRAIEGRTATSEYQTFFNPRTF THRB_HUMAN 308 6 -
DAAIEGRTSEDHFQPFFNEKTF THRB_BOVIN 311 8 -
VEEIAGRTIFQEFKTFFDEKTF Q91001 295 0 -

Motif 5 width=17
Element Seqn Id St Int Rpt
TEKELLDSYIDGRIVEG THRB_MOUSE 348 21 -
TEKELLDSYIDGRIVEG THRB_RAT 347 21 -
TERELLESYIDGRIVEG THRB_HUMAN 351 21 -
TEKELFESYIEGRIVEG THRB_BOVIN 354 21 -
SEKELMDSYMGGRVVHG Q91001 338 21 -

Motif 6 width=25
Element Seqn Id St Int Rpt
YPPWDKNFTENDLLVRIGKHSRTRY THRB_MOUSE 407 42 -
YPPWDKNFTENDLLVRIGKHSRTRY THRB_RAT 406 42 -
YPPWDKNFTENDLLVRIGKHSRTRY THRB_HUMAN 410 42 -
YPPWDKNFTVDDLLVRIGKHSRTRY THRB_BOVIN 413 42 -
YPPWDKNLTTNDILVRMGLHFRAKY Q91001 397 42 -

Motif 7 width=18
Element Seqn Id St Int Rpt
AGYKGRVTGWGNLRETWT THRB_MOUSE 492 60 -
AGYKGRVTGWGNLRETWT THRB_RAT 491 60 -
AGYKGRVTGWGNLKETWT THRB_HUMAN 495 60 -
AGFKGRVTGWGNRRETWT THRB_BOVIN 498 60 -
AGFKGRVTGWGNLKETWA Q91001 482 60 -

Motif 8 width=24
Element Seqn Id St Int Rpt
DRKGKYGFYTHVFRLKRWIQKVID THRB_MOUSE 592 82 -
DRNGKYGFYTHVFRLKRWMQKVID THRB_RAT 591 82 -
DRDGKYGFYTHVFRLKKWIQKVID THRB_HUMAN 595 82 -
DRDGKYGFYTHVFRLKKWIQKVID THRB_BOVIN 598 82 -
DRDGKYGFYTHVFRLKKWMRKTIE Q91001 581 81 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
LPWNSLPAKTLSKYQDF THRB_MOUSE 237 237 -
LAWDSLPTKTLSKYQNF THRB_RAT 237 237 -
LAWASAQAKALSKHQDF THRB_HUMAN 235 235 -
LAWSSEQAKALSKDQDF THRB_BOVIN 236 236 -
LPWASEKAKALLQDKTI Q91001 229 229 -

Motif 2 width=22
Element Seqn Id St Int Rpt
NFCRNPDWDEEGAWCYVAGQPG THRB_MOUSE 262 8 -
NFCRNPDRDEEGAWCFVAQQPG THRB_RAT 262 8 -
NFCRNPDGDEEGVWCYVAGKPG THRB_HUMAN 260 8 -
NFCRNPDGDEEGAWCYVADQPG THRB_BOVIN 261 8 -
NYCRNPDADDEGVWCVIDEPPY Q91001 254 8 -

Motif 3 width=19
Element Seqn Id St Int Rpt
FEYCNLNYCEEAVGEENYD THRB_MOUSE 285 1 -
FEYCSLNYCDEAVGEENHD THRB_RAT 284 0 -
FGYCDLNYCEEAVEEETGD THRB_HUMAN 283 1 -
FEYCDLNYCEEPVDGDLGD THRB_BOVIN 284 1 -
FEYCDLHYCDSSLEDENEQ Q91001 276 0 -

Motif 4 width=22
Element Seqn Id St Int Rpt
DESIAGRTTDAEFHTFFNEKTF THRB_MOUSE 305 1 -
DESIAGRTTDAEFHTFFDERTF THRB_RAT 304 1 -
DRAIEGRTATSEYQTFFNPRTF THRB_HUMAN 308 6 -
DAAIEGRTSEDHFQPFFNEKTF THRB_BOVIN 311 8 -
VEEIAGRTIFQEFKTFFDEKTF Q91001 295 0 -

Motif 5 width=17
Element Seqn Id St Int Rpt
TEKELLDSYIDGRIVEG THRB_MOUSE 348 21 -
TEKELLDSYIDGRIVEG THRB_RAT 347 21 -
TERELLESYIDGRIVEG THRB_HUMAN 351 21 -
TEKELFESYIEGRIVEG THRB_BOVIN 354 21 -
SEKELMDSYMGGRVVHG Q91001 338 21 -

Motif 6 width=25
Element Seqn Id St Int Rpt
YPPWDKNFTENDLLVRIGKHSRTRY THRB_MOUSE 407 42 -
YPPWDKNFTENDLLVRIGKHSRTRY THRB_RAT 406 42 -
YPPWDKNFTENDLLVRIGKHSRTRY THRB_HUMAN 410 42 -
YPPWDKNFTVDDLLVRIGKHSRTRY THRB_BOVIN 413 42 -
YPPWDKNLTTNDILVRMGLHFRAKY Q91001 397 42 -

Motif 7 width=18
Element Seqn Id St Int Rpt
AGYKGRVTGWGNLRETWT THRB_MOUSE 492 60 -
AGYKGRVTGWGNLRETWT THRB_RAT 491 60 -
AGYKGRVTGWGNLKETWT THRB_HUMAN 495 60 -
AGFKGRVTGWGNRRETWT THRB_BOVIN 498 60 -
AGFKGRVTGWGNLKETWA Q91001 482 60 -

Motif 8 width=24
Element Seqn Id St Int Rpt
DRKGKYGFYTHVFRLKRWIQKVID THRB_MOUSE 592 82 -
DRNGKYGFYTHVFRLKRWMQKVID THRB_RAT 591 82 -
DRDGKYGFYTHVFRLKKWIQKVID THRB_HUMAN 595 82 -
DRDGKYGFYTHVFRLKKWIQKVID THRB_BOVIN 598 82 -
DRDGKYGFYTHVFRLKKWMRKTIE Q91001 581 81 -