$VAR1 = undef;

Summary for peptidase S01.217: thrombin

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Substrates Pharma

Names
MEROPS Name	thrombin
Other names	coagulation 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
Holotype	thrombin (Homo sapiens), Uniprot accession P00734 (peptidase unit: 364-620), MERNUM MER0000188
History	Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.

Activity
Catalytic type	Serine
Peplist	Included in the Peplist with identifier PL00311
NC-IUBMB	Subclass 3.4 (Peptidases) >> Sub-subclass 3.4.21 (Serine endopeptidases) >> Peptidase 3.4.21.5
Enzymology	BRENDA database
Proteolytic events	CutDB database (49 cleavages)
Activity status	human: active (Le Bonniec, 2004) mouse: active (Sun et al., 1998)
Biotechnology	Reagent for cleavage of recombinant fusion proteins. Salmon thrombin has been proposed for application in mammalian wound healing (Michaud et al., 2002).
Physiology	Causes 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).
Knockout	Thrombin-deficient mice were found to be prone to fatal hemorrhagic events (Sun et al., 1998).
Pharmaceutical relevance	Thrombosis 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	KEGG	Complement and coagulation cascades
	KEGG	Neuroactive ligand-receptor interaction
	KEGG	Pathways in cancer
	KEGG	Regulation of actin cytoskeleton
Other databases	WIKIPEDIA	http://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	-/-/palg/Rsag/-/-/- (based on 195 cleavages)

Specificity matrix

Amino acid	P4	P3	P2	P1	P1'	P2'	P3'	P4'
Gly	14	15	20	0	26	8	23	16
Pro	14	3	79	0	0	8	10	9
Ala	36	15	21	0	28	17	10	13
Val	12	11	18	0	7	16	9	17
Leu	18	7	21	1	12	18	20	11
Ile	12	15	7	0	7	9	10	11
Met	10	4	1	0	1	2	1	0
Phe	6	5	4	0	4	14	3	6
Tyr	4	4	0	0	1	9	2	3
Trp	2	2	0	0	0	0	0	1
Ser	9	17	4	0	49	8	16	19
Thr	4	15	5	0	12	11	8	15
Cys	0	6	0	0	0	4	0	2
Asn	3	9	5	0	0	3	5	10
Gln	10	9	6	0	2	13	14	6
Asp	0	9	0	0	0	0	1	2
Glu	1	5	0	0	0	3	4	3
Lys	6	12	0	25	2	13	16	13
Arg	2	18	0	167	9	9	11	7
His	2	4	1	2	9	4	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	-	-	-	-	xIPRxxxx	ACC-Dabcyl	Sun et al., 2007
Homo sapiens	wild type	-	M/T/R	P/L	-	S	F/Y	R/K	-	xMPxSFRx	Abz-EDDnp	Bianchini et al., 2002
Homo sapiens	recombinant	-	-	-	-	-	F/W	K/W	-	xxxxxFKx	Abz-Dnp	Le Bonniec et al., 1996
Homo sapiens	recombinant	-	-	-	-	S	N/broad	R/broad	G/S	xxxSNRG	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