| IED ID | IndEnz0002011466 |
| Enzyme Type ID | protease011466 |
| Protein Name |
Zinc metalloproteinase-disintegrin-like jararhagin EC 3.4.24.73 HF2-proteinase JG Jararafibrase I JF I Snake venom metalloproteinase SVMP Cleaved into: Disintegrin-like jararhagin-C Jaracetin Fragment |
| Gene Name | |
| Organism | Bothrops jararaca (Jararaca) (Bothrops jajaraca) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Sauropsida Sauria (diapsids) Lepidosauria (lepidosaurs) Squamata (squamates) Bifurcata (split-tongued squamates) Unidentata Episquamata Toxicofera Serpentes (snakes) Colubroidea Viperidae Crotalinae (pit vipers) Bothrops Bothrops jararaca (Jararaca) (Bothrops jajaraca) |
| Enzyme Sequence | ATRPKGAVQPKYEDAMQYEFKVNGEPVVLHLEKNKGLFSKDYSEIHYSPDGREITTYPPVEDHCYYHGRIENDADSTASISACNGLKGYFKLQRETYFIEPLKLPDSEAHAVFKYENVEKEDEAPKMCGVTQNWKSYEPIKKASQLAFTAEQQRYDPYKYIEFFVVVDQGTVTKNNGDLDKIKARMYELANIVNEIFRYLYMHVALVGLEIWSNGDKITVKPDVDYTLNSFAEWRKTDLLTRKKHDNAQLLTAIDFNGPTIGYAYIGSMCHPKRSVGIVQDYSPINLVVAVIMAHEMGHNLGIHHDTGSCSCGDYPCIMGPTISNEPSKFFSNCSYIQCWDFIMNHNPECIINEPLGTDIISPPVCGNELLEVGEECDCGTPENCQNECCDAATCKLKSGSQCGHGDCCEQCKFSKSGTECRASMSECDPAEHCTGQSSECPADVFHKNGQPCLDNYGYCYNGNCPIMYHQCYALFGADVYEAEDSCFKDNQKGNYYGYCRKENGKKIPCAPEDVKCGRLYCKDNSPGQNNPCKMFYSNDDEHKGMVLPGTKCADGKVCSNGHCVDVATAY |
| Enzyme Length | 571 |
| Uniprot Accession Number | P30431 |
| Absorption | |
| Active Site | ACT_SITE 296; /evidence="ECO:0000255|PROSITE-ProRule:PRU00276, ECO:0000255|PROSITE-ProRule:PRU10095" |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by EDTA, 1,10 phenanthroline and batimastat (a peptidomimetic MMP inhibitor). {ECO:0000269|PubMed:14613713, ECO:0000269|PubMed:15530968}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Cleavage of 10-His-|-Leu-11, 14-Ala-|-Leu-15, 16-Tyr-|-Leu-17 and 24-Phe-|-Phe-25 bonds in insulin B chain.; EC=3.4.24.73; Evidence={ECO:0000269|PubMed:12165326}; |
| DNA Binding | |
| EC Number | 3.4.24.73 |
| Enzyme Function | FUNCTION: Snake venom zinc metalloproteinase-disintegrin-like jararhagin: causes hemorrhage. This is the result of the degradation of sub-endothelial matrix proteins leading to the disruption of the blood vessel endothelium, with accompanying disturbances in platelet function. It is able to degrade von Willebrand factor (vWF) and it hydrolyzes the alpha-chain of fibrinogen (FGA) while leaving the beta and gamma chains unaffected. It inhibits collagen-induced platelet aggregation through the binding to alpha-2/beta-1 integrin (ITGA2/ITGB1) (collagen receptor), and it cleaves the beta-1 subunit of the same integrin, inhibiting platelet interaction and ultimately causing impairment of signal transduction. It has inability to be affected by the plasma inhibitor alpha(2)-macroglobulin. In fibroblasts, it functions as a collagen-mimetic substrate and, in endothelial cells, it causes apoptosis and indirectly inhibits cell proliferation by release of angiostatin-like compounds. It induces a strong pro-inflammatory response characterized by intense leukocyte accumulation and release of cytokines at the site of the injection. Although hemorrhage and edema are a response to the direct effect of this toxin, jararhagin-induced inflammation and necrosis are dependent on macrophages and key pro-inflammatory cytokines or their receptors. It also possesses anti-tumorgenic properties.; FUNCTION: [Disintegrin-like jararhagin-C]: The monomeric form inhibits collagen- and ADP-induced platelet aggregation, but has no effect on glycoprotein Ib-IX-dependent (GP1BA/GP5/GP9) platelet agglutination. Locally activates the early events of an acute inflammatory response as leukocyte rolling and pro-inflammatory cytokine release.; FUNCTION: [Disintegrin-like jararhagin-C]: The dimeric form jaracetin may be a dimeric form of jararhagin-C. It binds to von Willebrand factor (VWF) and induces its interaction with GPIbalpha (GP1BA) (via the vWF A1 domain), resulting in platelet aggregation. Also binds the alpha-2 subunit of the alpha-2/beta-1 (ITGA2/ITGB1) integrin. It potently induces platelet aggregation in citrated platelet-rich plasma. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (2); Disulfide bond (25); Domain (2); Glycosylation (1); Metal binding (18); Modified residue (1); Motif (1); Non-terminal residue (1); Propeptide (1); Site (1) |
| Keywords | Apoptosis;Calcium;Cell adhesion impairing toxin;Direct protein sequencing;Disulfide bond;Fibrinogenolytic toxin;Glycoprotein;Hemorrhagic toxin;Hemostasis impairing toxin;Hydrolase;Metal-binding;Metalloprotease;Platelet aggregation activating toxin;Platelet aggregation inhibiting toxin;Protease;Pyrrolidone carboxylic acid;Secreted;Toxin;Zinc;Zymogen |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted. |
| Modified Residue | MOD_RES 151; /note=Pyrrolidone carboxylic acid (Glu); /evidence=ECO:0000250|UniProtKB:O93523 |
| Post Translational Modification | PTM: The N-terminus of Jararhagin is blocked. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | MOTIF 427..429; /note=D/ECD-tripeptide |
| Gene Encoded By | |
| Mass | 63,983 |
| Kinetics | |
| Metal Binding | METAL 162; /note=Calcium 1; /evidence=ECO:0000250; METAL 246; /note=Calcium 1; /evidence=ECO:0000250; METAL 295; /note=Zinc; catalytic; /evidence=ECO:0000305; METAL 299; /note=Zinc; catalytic; /evidence=ECO:0000305; METAL 305; /note=Zinc; catalytic; /evidence=ECO:0000305; METAL 350; /note=Calcium 1; via carbonyl oxygen; /evidence=ECO:0000250; METAL 353; /note=Calcium 1; /evidence=ECO:0000250; METAL 365; /note=Calcium 2; via carbonyl oxygen; /evidence=ECO:0000250; METAL 368; /note=Calcium 2; /evidence=ECO:0000250; METAL 370; /note=Calcium 2; via carbonyl oxygen; /evidence=ECO:0000250; METAL 372; /note=Calcium 2; /evidence=ECO:0000250; METAL 375; /note=Calcium 2; /evidence=ECO:0000250; METAL 378; /note=Calcium 2; /evidence=ECO:0000250; METAL 429; /note=Calcium 3; /evidence=ECO:0000250; METAL 430; /note=Calcium 3; via carbonyl oxygen; /evidence=ECO:0000250; METAL 432; /note=Calcium 3; /evidence=ECO:0000250; METAL 444; /note=Calcium 3; /evidence=ECO:0000250; METAL 445; /note=Calcium 3; via carbonyl oxygen; /evidence=ECO:0000250 |
| Rhea ID | |
| Cross Reference Brenda | 3.4.24.73; |