| IED ID |
IndEnz0002009456 |
| Enzyme Type ID |
protease009456 |
| Protein Name |
Kunitz-type neurotoxin MitTx-alpha
|
| Gene Name |
|
| Organism |
Micrurus tener tener (Texas coral snake) |
| 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
Elapidae
Elapinae
Micrurus (coral snakes)
Micrurus tener (Texas coral snake)
Micrurus tener tener (Texas coral snake)
|
| Enzyme Sequence |
MSSGGLLLLLGLLTLCAELTPVSSQIRPAFCYEDPPFFQKCGAFVDSYYFNRSRITCVHFFYGQCDVNQNHFTTMSECNRVCHG |
| Enzyme Length |
84 |
| Uniprot Accession Number |
G9I929 |
| Absorption |
|
| Active Site |
|
| Activity Regulation |
|
| Binding Site |
|
| Calcium Binding |
|
| catalytic Activity |
|
| DNA Binding |
|
| EC Number |
|
| Enzyme Function |
FUNCTION: MitTx, a heteromeric complex between Kunitz- and phospholipase-A2-like proteins, potently, persistently and selectively activates rat and chicken acid-sensing ion channel ASIC1 (PubMed:22094702, PubMed:24507937). Both alternatively spliced rat isoforms ASIC1a and ASIC1b are activated, with a higher potency for ASIC1a (EC(50)=9.4 nM) vs ASIC1b (EC(50)=23 nM) (PubMed:22094702). The rat ASIC3 subtype is also sensitive to the heterodimer, but with a lower potency (EC(50)=830 nM) (PubMed:22094702). On rat ASIC2a, the toxin shows a very weak activation, but produces a remarkable potentiation (>100-fold) of protons when the extracellular pH drops below neutrality (PubMed:22094702). Moderate and weak activations are also observed on the heterotrimers Asic1a-Asic2a and Asic1a-Asic3 (expressed in CHO cells), respectively (PubMed:22094702). The binding sites of the beta subunit of MitTx and the spider psalmotoxin-1 overlap, explaining why these toxins are mutually exclusive (PubMed:22094702. PubMed:24507937). In vivo, the heterodimer elicits robust pain-related behavior in mice by activation of ASIC1 channels on capsaicin-sensitive nerve fibers (PubMed:22094702). {ECO:0000269|PubMed:22094702, ECO:0000269|PubMed:24507937}. |
| Temperature Dependency |
|
| PH Dependency |
|
| Pathway |
|
| nucleotide Binding |
|
| Features |
Beta strand (4); Chain (1); Disulfide bond (3); Domain (1); Helix (2); Modified residue (1); Signal peptide (1); Turn (1) |
| Keywords |
3D-structure;Direct protein sequencing;Disulfide bond;Ion channel impairing toxin;Protease inhibitor;Proton-gated sodium channel impairing toxin;Pyrrolidone carboxylic acid;Secreted;Serine protease inhibitor;Signal;Toxin |
| Interact With |
|
| Induction |
|
| Subcellular Location |
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22094702}. |
| Modified Residue |
MOD_RES 25; /note=Pyrrolidone carboxylic acid; /evidence=ECO:0000269|PubMed:22094702 |
| Post Translational Modification |
|
| Signal Peptide |
SIGNAL 1..24; /evidence=ECO:0000269|PubMed:22094702 |
| Structure 3D |
X-ray crystallography (3) |
| Cross Reference PDB |
4NTW;
4NTX;
4NTY;
|
| Mapped Pubmed ID |
- |
| Motif |
|
| Gene Encoded By |
|
| Mass |
9,498 |
| Kinetics |
|
| Metal Binding |
|
| Rhea ID |
|
| Cross Reference Brenda |
|