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UniProt functional annotation for P45697 | ||
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| UniProt code: P45697. |
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| Organism: | |
Mesobuthus martensii (Manchurian scorpion) (Buthus martensii). |
| Taxonomy: | |
Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus. |
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| Function: | |
Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels thereby blocking neuronal transmission. This toxin is active against both mammals and insects, and is classified as an alpha-like toxin. It is active on Nav1.2/SCN2A (EC(50)=139-252 nM), Nav1.3/SCN3A (EC(50)=565 nM), Nav1.4/SCN4A and Nav1.5/SCN5A (EC(50)=195-500 nM), Nav1.6/SCN8A (EC(50)=214 nM), and drosophila DmNav1 (EC(50)=30 nM) (PubMed:11322948, PubMed:12705833, PubMed:15677695, PubMed:19162162, PubMed:20678086). In mNav1.6/SCN8A, the toxin induces a large increase in both transient and persistent currents, which correlates with a prominent reduction in the fast component of inactivating current (PubMed:20678086). In rNav1.2/SCN2A and rNav1.3/SCN3A, toxin-increased currents is much smaller (PubMed:19162162, PubMed:20678086). Moreover, the toxin only accelerates the slow inactivation development and delay recovery of mNav1.6/SCN8A through binding to the channel in the open state (PubMed:20678086). Is 6-fold more toxic than BmK-M2. In vivo, intrahippocampal injection into rat induces epileptiform responses (PubMed:16229835). In addition, intraplantar injection into rat induces spontaneous nociception and hyperalgesia (PubMed:14554105). {ECO:0000269|PubMed:11322948, ECO:0000269|PubMed:12705833, ECO:0000269|PubMed:14554105, ECO:0000269|PubMed:15677695, ECO:0000269|PubMed:16229835, ECO:0000269|PubMed:19162162, ECO:0000269|PubMed:20678086}. |
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| Subcellular location: | |
Secreted {ECO:0000269|PubMed:8896191}. |
| Tissue specificity: | |
Expressed by the venom gland. {ECO:0000305|PubMed:8896191}. |
| Domain: | |
Has the structural arrangement of an alpha-helix connected to antiparallel beta-sheets by disulfide bonds (CS-alpha/beta). {ECO:0000269|PubMed:10493862, ECO:0000269|PubMed:15321715, ECO:0000269|PubMed:16209876}. |
| Toxic dose: | |
LD(50) is 0.75 mg/kg by intravenous injection into mice. {ECO:0000269|PubMed:12705833}. |
| Toxic dose: | |
LD(50) is 0.53 mg/kg by intravenous injection into tail mice. {ECO:0000269|PubMed:12705833, ECO:0000269|PubMed:15677695}. |
| Miscellaneous: | |
Exists in two forms, due to cis-trans isomerization at 28-Pro-His-29. {ECO:0000269|PubMed:15321715}. |
| Miscellaneous: | |
Has insignificant effect on Nav1.2/SCN2A. {ECO:0000269|PubMed:12705833, ECO:0000269|PubMed:15677695}. |
| Similarity: | |
Belongs to the long (4 C-C) scorpion toxin superfamily. Sodium channel inhibitor family. Alpha subfamily. {ECO:0000305}. |
| Sequence caution: | |
Sequence=AAA69557.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; |
Annotations taken from UniProtKB at the EBI.