Summary for peptidase S01.217: thrombin

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS Namethrombin
Other namescoagulation factor II, F2 g.p. (Homo sapiens) (activated), fibrinogenase, meizothrombin, prothrombin
Domain architecture
MEROPS Classification
Classification Clan PA >> Subclan PA(S) >> Family S1 >> Subfamily A >> S01.217
Holotypethrombin (Homo sapiens), Uniprot accession P00734 (peptidase unit: 364-620), MERNUM MER0000188
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeSerine
PeplistIncluded in the Peplist with identifier PL00311
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.21 (Serine endopeptidases) >> Peptidase 3.4.21.5
EnzymologyBRENDA database
Proteolytic eventsCutDB database (49 cleavages)
Activity statushuman: active (Le Bonniec, 2004)
mouse: active (Sun et al., 1998)
BiotechnologyReagent for cleavage of recombinant fusion proteins. Salmon thrombin has been proposed for application in mammalian wound healing (Michaud et al., 2002).
PhysiologyCauses clotting of blood by limited proteolysis of fibrinogen. Genetic variant (G20210A) may be thrombotic risk factor. Thrombin also contributes to the activation of factor XIII by cleaving the activation peptide at the R37-G38 peptide bond (Isetti & Maurer, 2004).
KnockoutThrombin-deficient mice were found to be prone to fatal hemorrhagic events (Sun et al., 1998).
Pharmaceutical relevanceThrombosis is the most common cause of death in the industrialized world and, whether through venous thromboembolism, myocardial infarction or stroke, ultimately involves the inappropriate activity of thrombin (Huntington & Baglin, 2003). Thrombin is therefore an important drug target (Bostrom et al., 2003).
Pathways KEGGComplement and coagulation cascades
KEGGNeuroactive ligand-receptor interaction
KEGGPathways in cancer
KEGGRegulation of actin cytoskeleton
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Thrombin
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/pag/RScissile bondsag/-/-/- (based on 186 cleavages)
weblogo
Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 14 14 20 0 25 8 20 16
Pro 14 3 75 0 1 8 10 9
Ala 33 15 21 1 28 16 9 13
Val 11 11 16 0 5 16 10 17
Leu 15 7 19 1 10 18 20 11
Ile 11 15 7 0 7 9 9 11
Met 10 4 1 0 1 2 1 0
Phe 7 5 4 0 3 13 3 5
Tyr 4 4 0 0 1 9 2 3
Trp 2 2 0 0 0 0 0 1
Ser 9 14 3 0 45 8 16 17
Thr 3 15 4 0 11 10 8 14
Cys 0 6 0 0 0 4 0 1
Asn 3 8 5 0 0 3 5 8
Gln 10 9 7 0 2 11 13 6
Asp 0 8 0 1 0 0 1 2
Glu 1 5 0 0 0 3 2 3
Lys 6 11 1 23 2 11 15 13
Arg 1 17 0 159 10 8 10 5
His 2 3 0 1 9 3 6 4
Specificity from combinatorial peptides
 
Organism comment P4 P3 P2 P1 P1' P2' P3' P4' optimal substrate fluorophore or acceptor-donor pair Reference
Homo sapiens recombinant n/L/I T/W/broad P R - - - - nTPR ACC Harris et al., 2000
Homo sapiens recombinant n/I/V/broad K/R/Q/V P/A R - - - - nKPR AMC Edwards et al., 2000
Homo sapiens recombinant n/I/L/broad K/R/Q/L P/A R - - - - nKPR AMC Furlong et al., 2002
Bos taurus wild type - I/S/T P/R/N/I R/K/N/Q - - - - xIPR+xxxx ACC-Dabcyl Sun et al., 2007
Homo sapiens wild type - M/T/R P/L - S F/Y R/K - xMPx+SFRx Abz-EDDnp Bianchini et al., 2002
Homo sapiens recombinant - - - - - F/W K/W - xxxx+xFKx Abz-Dnp Le Bonniec et al., 1996
Homo sapiens recombinant - - - - S N/broad R/broad G/S xxx+SNRG AMC-Dnp Petrassi et al., 2005
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
F2 11p11-q12 ENSG00000180210 2147 F2 176930
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
F2 2:E1 ENSMUSG00000027249 14061 MGI:88380