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PR00907

Identifier
THRMBOMODULN  [View Relations]  [View Alignment]  
Accession
PR00907
No. of Motifs
9
Creation Date
07-JUN-1998  (UPDATE 07-JUN-1999)
Title
Thrombomodulin signature
Database References

PROSITE; PS00022 EGF_1; PS01187 EGF_CA
INTERPRO; IPR001491
PDB; 1HLT
SCOP; 1HLT
CATH; 1HLT
Literature References
1. GERLITZ, B., HASSELL, T., VLAHOS, C.J., PARKINSON, J.F., BANG, N.U.
AND GRINNELL, B.W.
Identification of the predominant glycosaminoglycan-attachment site in
soluble recombinant human thrombomodulin: potential regulation of
functionality by glycosyltransferase competition for serine474. 
BIOCHEM.J. 295 131-140 (1993). 
 
2. DITTMAN W.A., KUMADA T., SADLER J.E., MAJERUS P.W.
The structure and function of mouse thrombomodulin. Phorbol myristate
acetate stimulates degradation and synthesis of thrombomodulin without
affecting mRNA levels in hemangioma cells. 
J.BIOL.CHEM. 263 15815-15822 (1988). 
 
3. HRABAL, R., KOMIVES, E.A. AND NI, F.
Structural resiliency of an EGF-like subdomain bound to its target protein,
thrombin. 
PROTEIN SCI. 5 195-203 (1996). 

Documentation
Thrombomodulin (TM) is an endothelial cell thrombin receptor that converts
thrombin from a procoagulant to an anticoagulant enzyme [1,2]. The deduced
amino acid sequence of mouse thrombomodulin is similar to those determined 
for human and bovine proteins.
 
The thrombin-bound structures of peptide fragments from the fifth EGF-like
domain of thrombomodulin have been determined by NMR and transferred NOE
spectroscopy [3]. The peptides assume an EGF-like structure, with an anti-
parallel beta-sheet, which shows structural resilience in accommodating 
different numbers of residues within its disulphide loop [3]. The key
contacts with thrombin are hydrophobic interactions between the side chains
of residues Ile 414 and Ile 424 of thrombomodulin and a hydrophobic pocket
on the thrombin surface [3]. The unique beta-sheet structures of the bound
peptides are specified by the presence of disulphide bridges; corresponding
linear thrombomodulin fragments fold into sheet structures with different
backbone topologies [3].
 
THRMBOMODULN is a 9-element fingerprint that provides a signature for
thrombomodulins. The fingerprint was derived from an initial alignment of
5 sequences: the motifs were drawn from conserved regions spanning 
the C-terminal half of the alignment length - motifs 1-3 span the first
EGF-like domain; motif 4 includes the C-terminus of the third EGF-like 
(putative calcium-binding) domain; motif 5 lies in the fourth EGF-like
domain; motif 6 lies in the sixth EGF-like domain; motif 7 includes the
sixth EGF-like (putative calcium-binding) domain; motif 8 spans the 
putative transmembrane domain; and motif 9 lies at the C-terminus. A single
iteration on OWL30.2 was required to reach convergence, no further sequences
being identified beyond the starting set. A single partial match was found,
MMU20217, a mouse fibrillin that matches motif 5 and 7. 
 
An update on SPTR37_9f identified a true set of 3 sequences.
Summary Information
3 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
9333333333
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
O35370        TRBM_HUMAN    TRBM_MOUSE    
Sequence Titles
O35370      THROMBOMODULIN - RATTUS NORVEGICUS (RAT).     
TRBM_HUMAN THROMBOMODULIN PRECURSOR (FETOMODULIN) (TM) (CD141 ANTIGEN) - HOMO SAPIENS (HUMAN).
TRBM_MOUSE THROMBOMODULIN PRECURSOR (FETOMODULIN) (TM) - MUS MUSCULUS (MOUSE).
Scan History
OWL30_2    1  50   NSINGLE    
SPTR37_9f 2 4 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
GHWAREAPGAWDCSVENGGC TRBM_HUMAN 233 233 -
GHWTREVTGAWNCSVENGGC AF022743 232 232 -
GRWSREAPGAWACGVERGGC TRBM_BOVIN 9 9 -
GHWTREVTGAWNCSVENGGC RNU90121 116 116 -
GHWAWEATGAWNCSVENGGC TRBM_MOUSE 232 232 -

Motif 2 width=17
Element Seqn Id St Int Rpt
CEYLCNRSTNEPRCLCP TRBM_MOUSE 251 -1 -
CEYMCNRSANGPRCVCP AF022743 251 -1 -
CEYMCNRSANGPRCVCP RNU90121 135 -1 -
CQHECKGSAGASNCLCP TRBM_BOVIN 28 -1 -
CEHACNAIPGAPRCQCP TRBM_HUMAN 252 -1 -

Motif 3 width=24
Element Seqn Id St Int Rpt
LQADGRSCGLPAEHPCHQLCEHFC TRBM_BOVIN 49 4 -
LQADGRSCAKPVGQLCNELCQHFC RNU90121 156 4 -
LQADGRSCARPVVQSCNELCEHFC TRBM_MOUSE 272 4 -
LQADGRSCTASATQSCNDLCEHFC TRBM_HUMAN 273 4 -
LQADGRSCAKPVAQLCNELCQHFC AF022743 272 4 -

Motif 4 width=26
Element Seqn Id St Int Rpt
GGFECRCYDGYELVDGECVEQLDPCF AF022743 344 48 -
GGFQCHCDTGYELVDGECVDPVDPCF TRBM_BOVIN 119 46 -
GGFECHCYPNYDLVDGECVEPVDPCF TRBM_HUMAN 345 48 -
GGFECFCYDGYELVDGECVELLDPCF TRBM_MOUSE 344 48 -
GGFECRCYDGYELVDGECVEQLDPCF RNU90121 228 48 -

Motif 5 width=23
Element Seqn Id St Int Rpt
CEYQCQPVNSTHYNCICAEGFAP RNU90121 257 3 -
CEYQCQPVNSTHYNCICAEGFAP AF022743 373 3 -
CEYQCQPVGRSEHKCICAEGFAP TRBM_BOVIN 148 3 -
CEYQCQPLNQTSYLCVCAEGFAP TRBM_HUMAN 374 3 -
CEFQCQPVSPTDYRCICAPGFAP TRBM_MOUSE 373 3 -

Motif 6 width=19
Element Seqn Id St Int Rpt
PHKCQMFCNQTSCPADCDP TRBM_BOVIN 175 4 -
PDRCEMFCNETSCPADCDP AF022743 400 4 -
PDRCEMFCNETSCPADCDP RNU90121 284 4 -
PHKCEMFCNETSCPADCDP TRBM_MOUSE 400 4 -
PHRCQMFCNQTACPADCDP TRBM_HUMAN 401 4 -

Motif 7 width=27
Element Seqn Id St Int Rpt
CRNFPGSYECICGPDTALAGQISKDCD TRBM_MOUSE 454 35 -
CHNLPGTYECICGPDSALSGQIGIDCD TRBM_BOVIN 228 34 -
CRNLPGSYECICGPDTALAGQISKDCD RNU90121 338 35 -
CRNLPGSYECICGPDTALAGQISKDCD AF022743 454 35 -
CHNLPGTFECICGPDSALARHIGTDCD TRBM_HUMAN 455 35 -

Motif 8 width=25
Element Seqn Id St Int Rpt
HSGVLVGISIASLSLVVALLALLCH TRBM_BOVIN 295 40 -
HSGVLIGISIASLSLVVALLALLCH TRBM_MOUSE 516 35 -
HSGLLIGISIASLCLVVALLALLCH TRBM_HUMAN 514 32 -
HSGVLIGISIASLSLVVALLALLCH AF022743 516 35 -
HSGVLIGISIASLSLVVALLALLCH RNU90121 400 35 -

Motif 9 width=25
Element Seqn Id St Int Rpt
RAELEYKCTSSAKEVLLQHVRTDRT RNU90121 433 8 -
RAELEYKCASSAKEVVLQHVRTDRT TRBM_MOUSE 549 8 -
RAKMEYKCAAPSKEVVLQHVRTERT TRBM_HUMAN 547 8 -
RGELEYKCGVPAKELMLQQVKTERT TRBM_BOVIN 328 8 -
RAELEYKCTSSAKEVVLQHVRTDRT AF022743 549 8 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
GHWTREVTGAWNCSVENGGC O35370 232 232 -
GHWAWEATGAWNCSVENGGC TRBM_MOUSE 232 232 -
GHWAREAPGAWDCSVENGGC TRBM_HUMAN 233 233 -

Motif 2 width=17
Element Seqn Id St Int Rpt
CEYMCNRSANGPRCVCP O35370 251 -1 -
CEYLCNRSTNEPRCLCP TRBM_MOUSE 251 -1 -
CEHACNAIPGAPRCQCP TRBM_HUMAN 252 -1 -

Motif 3 width=24
Element Seqn Id St Int Rpt
LQADGRSCAKPVAQLCNELCQHFC O35370 272 4 -
LQADGRSCARPVVQSCNELCEHFC TRBM_MOUSE 272 4 -
LQADGRSCTASATQSCNDLCEHFC TRBM_HUMAN 273 4 -

Motif 4 width=26
Element Seqn Id St Int Rpt
GGFECRCYDGYELVDGECVEQLDPCF O35370 344 48 -
GGFECFCYDGYELVDGECVELLDPCF TRBM_MOUSE 344 48 -
GGFECHCYPNYDLVDGECVEPVDPCF TRBM_HUMAN 345 48 -

Motif 5 width=23
Element Seqn Id St Int Rpt
CEYQCQPVNSTHYNCICAEGFAP O35370 373 3 -
CEFQCQPVSPTDYRCICAPGFAP TRBM_MOUSE 373 3 -
CEYQCQPLNQTSYLCVCAEGFAP TRBM_HUMAN 374 3 -

Motif 6 width=19
Element Seqn Id St Int Rpt
PDRCEMFCNETSCPADCDP O35370 400 4 -
PHKCEMFCNETSCPADCDP TRBM_MOUSE 400 4 -
PHRCQMFCNQTACPADCDP TRBM_HUMAN 401 4 -

Motif 7 width=27
Element Seqn Id St Int Rpt
CRNLPGSYECICGPDTALAGQISKDCD O35370 454 35 -
CRNFPGSYECICGPDTALAGQISKDCD TRBM_MOUSE 454 35 -
CHNLPGTFECICGPDSALARHIGTDCD TRBM_HUMAN 455 35 -

Motif 8 width=25
Element Seqn Id St Int Rpt
HSGVLIGISIASLSLVVALLALLCH O35370 516 35 -
HSGVLIGISIASLSLVVALLALLCH TRBM_MOUSE 516 35 -
HSGLLIGISIASLCLVVALLALLCH TRBM_HUMAN 514 32 -

Motif 9 width=25
Element Seqn Id St Int Rpt
RAELEYKCTSSAKEVVLQHVRTDRT O35370 549 8 -
RAELEYKCASSAKEVVLQHVRTDRT TRBM_MOUSE 549 8 -
RAKMEYKCAAPSKEVVLQHVRTERT TRBM_HUMAN 547 8 -