Evidence 1
Activity
Activity
Neurotoxin
FUNCTION: Inhibits many voltage-gated sodium channels and one voltage-gated calcium channel (Cav2.2/CACNA1B (IC(50)=400 nM), Nav1.2/SCN2A (IC(50)=3-70 nM), Nav1.1/SCN1A (IC(50)=523-1060 nM), Nav1.7/SCN9A (IC(50)=129.1-5120 nM), Nav1.4/SCN4A (IC(50)=263-888 nM or >10 uM) and Nav1.5/SCN5A (IC(50)=188-323 nM or >10 uM)) (PubMed:16267209, PubMed:27129258, PubMed:28880874, PubMed:29703751). It acts by shifting the voltage dependence of channel activation to more depolarized potentials and by blocking the inward component of the sodium current (PubMed:16267209). It shows moderate affinity for lipid bilayers (PubMed:29703751). On Nav1.7/SCN9A, it has been shown to interact with the S3-S4 loop of domain DII (site 4) (PubMed:27129258). Is significantly more potent against Nav1.2/SCN2A than the other Nav channel subtypes (PubMed:16267209). In vivo, this toxin causes general ataxia, lack of response to stimuli, and semiparalysis (PubMed:16267209). After a few minutes, the mice are unable to stand, and breathing is reduced in rhythm and intensity (PubMed:16267209). Symptoms gradually increase with progressive slowing of breathing and flaccid paralysis, death occurred within 10 to 20 minutes post injection (PubMed:16267209). Animals remain totally flaccid, and no symptoms of excitatory neurotoxicity are observed (PubMed:16267209). {ECO:0000269|PubMed:16267209, ECO:0000269|PubMed:27129258, ECO:0000269|PubMed:28880874, ECO:0000269|PubMed:29703751}.
Target
voltage-gated sodium channel (Nav)
voltage-gated calcium channel (Cav)
Source & Reference
NA
UniProtKB/Swiss-Prot Tox-Prot
Other
Ceratogyrus marshalli (Straighthorned baboon tarantula) (Ceratogyrus cornuatus)
Neurotoxin
Calcium channel impairing toxin
Ion channel impairing toxin
Voltage-gated calcium channel impairing toxin
Voltage-gated sodium channel impairing toxin
Inhibits many voltage-gated sodium channels and one voltage-gated calcium channel (Cav2.2/CACNA1B (IC(50)=400 nM), Nav1.2/SCN2A (IC(50)=3-70 nM), Nav1.1/SCN1A (IC(50)=523-1060 nM), Nav1.7/SCN9A (IC(50)=129.1-5120 nM), Nav1.4/SCN4A (IC(50)=263-888 nM or >10 uM) and Nav1.5/SCN5A (IC(50)=188-323 nM or >10 uM)) (PubMed:16267209, PubMed:27129258, PubMed:28880874, PubMed:29703751). It acts by shifting the voltage dependence of channel activation to more depolarized potentials and by blocking the inward component of the sodium current (PubMed:16267209).
Beta-theraphotoxin-Cm1a (Beta-TRTX-Cm1a) (CcoTx-I) (Ceratotoxin-1) (CcoTx1)
spider
Neurotoxin 10 (Hwtx-1) family, 04 (CcoTx1) subfamily
Evidence at protein level
3D-structure
Amidation
Calcium channel impairing toxin
Direct protein sequencing
Disulfide bond
Ion channel impairing toxin
Knottin
Neurotoxin
Pharmaceutical
Secreted
Toxin
Voltage-gated calcium channel impairing toxin
Voltage-gated sodium channel impairing toxin
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:16267209}.