UniProt functional annotation for P50983



	UniProt functional annotation for P50983

UniProt code: P50983.

Organism: Conus imperialis (Imperial cone).

Taxonomy: Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda; Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Stephanoconus.

Function: Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks neuronal alpha-3-beta-2/CHRNA3-CHRNB2 (human and rat), alpha-7/CHRNA7 (human and rat), and alpha-3-beta-4/CHRNA3-CHRNB4 (human) nAChRs (PubMed:8206995, PubMed:15609996, PubMed:19131337). Acts voltage-independently (PubMed:15609996). Competes with alpha- bungarotoxin for binding to the receptor (PubMed:12384509, PubMed:15609996). Binds to a different site than alpha-conotoxin ImII (PubMed:15609996). Is highly active against the neuromuscular receptor in frog (PubMed:8206995). Also exhibits inhibition of D.melanogaster alpha-7 nAChRs (PubMed:25466886). {ECO:0000269|PubMed:12384509, ECO:0000269|PubMed:15609996, ECO:0000269|PubMed:19131337, ECO:0000269|PubMed:25466886, ECO:0000269|PubMed:8206995}.

Subcellular location: Secreted {ECO:0000269|PubMed:8206995}.

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

Domain: The cysteine framework is I (CC-C-C). Alpha4/3 pattern. {ECO:0000305}.

Ptm: Not hydroxylated; hydroxylation improves its folding but impairs its activity against target receptors. {ECO:0000269|PubMed:18189422}.

Mass spectrometry: Mass=1351.48; Method=Unknown; Note=Monoisotopic mass.; Evidence={ECO:0000269|PubMed:8206995};

Miscellaneous: This toxin is a substrate for a multienzyme complex that regulates its folding and assembly. This complex is composed of protein-disulfide isomerase (PDI), peptidyl-prolyl cis-trans isomerase (PPI) and immunoglobulin-binding protein (BiP). PDI catalyzes the oxidation and reduction of disulfide bonds. Oxidative folding rates are further increased in the presence of PPI with the maximum effect observed in the presence of both enzymes. In contrast, BiP is only observed to assist folding in the presence of microsomes, suggesting that additional cofactors are involved. This toxin has been observed in the venom as globular (disulfide pattern C1-C3 and C2-C4) and ribbon form (C1-C4 and C2-C3). {ECO:0000269|PubMed:22891240}.

Miscellaneous: Does not inhibit alpha-2-beta-2, alpha-4-beta-2, alpha- 2-beta-4, alpha-3-beta-4, and alpha-4-beta-4 subunits (PubMed:7651351, PubMed:15609996). Has also no effect on muscle nAChRs alpha-1-beta-1- delta-epsilon (PubMed:15609996). {ECO:0000269|PubMed:15609996, ECO:0000269|PubMed:7651351}.

Similarity: Belongs to the conotoxin A superfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Conus imperialis (Imperial cone).
Taxonomy:		Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda; Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Stephanoconus.



Function:		Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks neuronal alpha-3-beta-2/CHRNA3-CHRNB2 (human and rat), alpha-7/CHRNA7 (human and rat), and alpha-3-beta-4/CHRNA3-CHRNB4 (human) nAChRs (PubMed:8206995, PubMed:15609996, PubMed:19131337). Acts voltage-independently (PubMed:15609996). Competes with alpha- bungarotoxin for binding to the receptor (PubMed:12384509, PubMed:15609996). Binds to a different site than alpha-conotoxin ImII (PubMed:15609996). Is highly active against the neuromuscular receptor in frog (PubMed:8206995). Also exhibits inhibition of D.melanogaster alpha-7 nAChRs (PubMed:25466886). {ECO:0000269\|PubMed:12384509, ECO:0000269\|PubMed:15609996, ECO:0000269\|PubMed:19131337, ECO:0000269\|PubMed:25466886, ECO:0000269\|PubMed:8206995}.


Subcellular location:		Secreted {ECO:0000269\|PubMed:8206995}.
Tissue specificity:		Expressed by the venom duct. {ECO:0000305}.
Domain:		The cysteine framework is I (CC-C-C). Alpha4/3 pattern. {ECO:0000305}.
Ptm:		Not hydroxylated; hydroxylation improves its folding but impairs its activity against target receptors. {ECO:0000269\|PubMed:18189422}.
Mass spectrometry:		Mass=1351.48; Method=Unknown; Note=Monoisotopic mass.; Evidence={ECO:0000269\|PubMed:8206995};
Miscellaneous:		This toxin is a substrate for a multienzyme complex that regulates its folding and assembly. This complex is composed of protein-disulfide isomerase (PDI), peptidyl-prolyl cis-trans isomerase (PPI) and immunoglobulin-binding protein (BiP). PDI catalyzes the oxidation and reduction of disulfide bonds. Oxidative folding rates are further increased in the presence of PPI with the maximum effect observed in the presence of both enzymes. In contrast, BiP is only observed to assist folding in the presence of microsomes, suggesting that additional cofactors are involved. This toxin has been observed in the venom as globular (disulfide pattern C1-C3 and C2-C4) and ribbon form (C1-C4 and C2-C3). {ECO:0000269\|PubMed:22891240}.
Miscellaneous:		Does not inhibit alpha-2-beta-2, alpha-4-beta-2, alpha- 2-beta-4, alpha-3-beta-4, and alpha-4-beta-4 subunits (PubMed:7651351, PubMed:15609996). Has also no effect on muscle nAChRs alpha-1-beta-1- delta-epsilon (PubMed:15609996). {ECO:0000269\|PubMed:15609996, ECO:0000269\|PubMed:7651351}.
Similarity:		Belongs to the conotoxin A superfamily. {ECO:0000305}.