UniProt functional annotation for P60615



	UniProt functional annotation for P60615

UniProt codes: P60615, P01378.

Organism: Bungarus multicinctus (Many-banded krait).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Serpentes; Colubroidea; Elapidae; Bungarinae; Bungarus.

Function: Binds with high affinity to muscular (tested on Torpedo marmorata, Kd=0.4 nM) and neuronal (tested on chimeric alpha-7/CHRNA7, Kd=0.95 nM) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission (PubMed:9305882). It also shows an activity on GABA(A) receptors (PubMed:16549768, PubMed:25634239). It antagonises GABA-activated currents with high potency when tested on primary hippocampal neurons (PubMed:25634239). It inhibits recombinantly expressed GABA(A) receptors composed of alpha-2-beta-2- gamma-2 (GABRA2-GABRB2-GABRG2) subunits with high potency (62.3% inhibition at 20 uM of toxin) (PubMed:25634239). It also shows a weaker inhibition on GABA(A) receptors composed of alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2) subunits, alpha-4-beta-2-gamma-2 (GABRA4-GABRB2- GABRG2) subunits, and alpha-5-beta-2-gamma-2 (GABRA5-GABRB2-GABRG2) subunits (PubMed:25634239). A very weak inhibition is also observed on GABA(A) receptor composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3- GABRG2) (PubMed:26221036). It has also been shown to bind and inhibit recombinant GABA(A) receptor beta-3/GABRB3 subunit (Kd=about 50 nM) (PubMed:16549768). In addition, it blocks the extracellular increase of dopamine evoked by nicotine only at the higher dose (4.2 uM) (PubMed:9840221). In vivo, when intraperitoneally injected into mice, induces flaccid paralysis of the limbs and respiratory distress, and causes death in a dose-dependent manner. {ECO:0000269|PubMed:16549768, ECO:0000269|PubMed:25634239, ECO:0000269|PubMed:9305882, ECO:0000269|PubMed:9840221}.

Subunit: Monomer in solution, homodimer in crystal state. {ECO:0000269|PubMed:11312275, ECO:0000269|PubMed:11381118, ECO:0000269|PubMed:11790782, ECO:0000269|PubMed:11814338, ECO:0000269|PubMed:12160749}.

Subcellular location: Secreted {ECO:0000269|PubMed:5027709}.

Tissue specificity: Expressed by the venom gland. {ECO:0000305}.

Toxic dose: LD(50) is 0.3 mg/kg by subcutaneous injection.

Miscellaneous: Is identical to Alpha-bungarotoxin (A31) from B.candidus (AC Q7T3J2). {ECO:0000305}.

Similarity: Belongs to the snake three-finger toxin family. Long-chain subfamily. Type II alpha-neurotoxin sub-subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Bungarus multicinctus (Many-banded krait).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Serpentes; Colubroidea; Elapidae; Bungarinae; Bungarus.



Function:		Binds with high affinity to muscular (tested on Torpedo marmorata, Kd=0.4 nM) and neuronal (tested on chimeric alpha-7/CHRNA7, Kd=0.95 nM) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission (PubMed:9305882). It also shows an activity on GABA(A) receptors (PubMed:16549768, PubMed:25634239). It antagonises GABA-activated currents with high potency when tested on primary hippocampal neurons (PubMed:25634239). It inhibits recombinantly expressed GABA(A) receptors composed of alpha-2-beta-2- gamma-2 (GABRA2-GABRB2-GABRG2) subunits with high potency (62.3% inhibition at 20 uM of toxin) (PubMed:25634239). It also shows a weaker inhibition on GABA(A) receptors composed of alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2) subunits, alpha-4-beta-2-gamma-2 (GABRA4-GABRB2- GABRG2) subunits, and alpha-5-beta-2-gamma-2 (GABRA5-GABRB2-GABRG2) subunits (PubMed:25634239). A very weak inhibition is also observed on GABA(A) receptor composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3- GABRG2) (PubMed:26221036). It has also been shown to bind and inhibit recombinant GABA(A) receptor beta-3/GABRB3 subunit (Kd=about 50 nM) (PubMed:16549768). In addition, it blocks the extracellular increase of dopamine evoked by nicotine only at the higher dose (4.2 uM) (PubMed:9840221). In vivo, when intraperitoneally injected into mice, induces flaccid paralysis of the limbs and respiratory distress, and causes death in a dose-dependent manner. {ECO:0000269\|PubMed:16549768, ECO:0000269\|PubMed:25634239, ECO:0000269\|PubMed:9305882, ECO:0000269\|PubMed:9840221}.


Subunit:		Monomer in solution, homodimer in crystal state. {ECO:0000269\|PubMed:11312275, ECO:0000269\|PubMed:11381118, ECO:0000269\|PubMed:11790782, ECO:0000269\|PubMed:11814338, ECO:0000269\|PubMed:12160749}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:5027709}.
Tissue specificity:		Expressed by the venom gland. {ECO:0000305}.
Toxic dose:		LD(50) is 0.3 mg/kg by subcutaneous injection.
Miscellaneous:		Is identical to Alpha-bungarotoxin (A31) from B.candidus (AC Q7T3J2). {ECO:0000305}.
Similarity:		Belongs to the snake three-finger toxin family. Long-chain subfamily. Type II alpha-neurotoxin sub-subfamily. {ECO:0000305}.