| IED ID | IndEnz0002010050 |
| Enzyme Type ID | protease010050 |
| Protein Name |
PI-stichotoxin-Hcr2f PI-SHTX-Hcr2f Kunitz-type serine protease inhibitor HCRG1 |
| Gene Name | |
| Organism | Heteractis crispa (Leathery sea anemone) (Radianthus macrodactylus) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Cnidaria Anthozoa (anthozoans) Hexacorallia Actiniaria (sea anemones) Stichodactylidae Heteractis Heteractis crispa (Leathery sea anemone) (Radianthus macrodactylus) |
| Enzyme Sequence | RGICSEPKVVGPCKAGLRRFYYDSETGECKPFIYGGCKGNKNNFETLHACRGICRA |
| Enzyme Length | 56 |
| Uniprot Accession Number | C0HJU6 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Dual-function toxin that inhibits both serine proteases and voltage-gated potassium channels (PubMed:26404319, PubMed:33158163). Has potent activity on both trypsin (Ki=28 nM) and chymotrypsin (Kd=1.8 nM) (PubMed:26404319). Shows inhibitory activity against 4 of the 7 potassium channels tested (rKv1.1/KCNA1; IC(50)=142.6 nM, hKv1.3/KCNA3; IC(50)=40.7 nM, rKv1.6/KCNA6; IC(50)=154.9 nM and drosophila Shaker; IC(50)=433.1 nM) (PubMed:33158163). Has an anti-inflammatory effect in LPS-activated macrophages in vitro, specifically reducing release of TNF and IL6 but not nitric oxide and reducing expression of IL1B precursor (PubMed:26404319). In contrast to some paralogs, this protein decreases reactive oxygen species (ROS) level in the oxidative stress agent 6-hydroxydopamine (6-OHDA)-induced neurotoxicity model, but does not show cytoprotective activity on neuroblastoma cells (PubMed:33802055). This protein also shows a weak free-radical scavenging activity (PubMed:33802055). In vivo, when tested in a mice model of acute local inflammation, it reduces paw edema during 24 hours. In addition, it also reduces the synthesis of TNF in this model (PubMed:33158163). {ECO:0000269|PubMed:26404319, ECO:0000269|PubMed:33158163}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Chain (1); Disulfide bond (3); Domain (1); Site (1) |
| Keywords | Direct protein sequencing;Disulfide bond;Ion channel impairing toxin;Nematocyst;Potassium channel impairing toxin;Protease inhibitor;Secreted;Serine protease inhibitor;Toxin;Voltage-gated potassium channel impairing toxin |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26404319}. Nematocyst {ECO:0000269|PubMed:26404319}. |
| Modified Residue | |
| Post Translational Modification | PTM: Contains 3 disulfide bonds. {ECO:0000269|PubMed:26404319}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 6,202 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |