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UniProtKB - P0DL68 (CA1A_CONLM)
Protein
Alpha-conotoxin LsIA
Gene
N/A
Organism
Conus limpusi (Cone snail)
Status
Functioni
Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This globular toxin inhibits human alpha-7/CHRNA7 (IC50=0.3-10.1 nM), rat alpha-3-beta-2/CHRNA3-CHRNB2 (IC50=10.3 nM) and rat alpha-3-alpha-5-beta-2/CHRNA3-CHRNB5-CHRNB2 (IC50=31.2 nM).
2 PublicationsMiscellaneous
Shows a weak inhibition of alpha-3-beta-4/CHRNA3-CHRNB4 nAChR and does not inhibit alpha-9-alpha-10/CHRNA9-CHRNA10, alpha-4-beta-2/CHRNA4-CHRNB2 and alpha-4-beta-4/CHRNA4-CHRNB4 nAChR.1 Publication
The synthetic ribbon toxin is much less potent that the globular toxin (IC50=41 nM compared to 0.3 nM).1 Publication
GO - Molecular functioni
- acetylcholine receptor inhibitor activity Source: UniProtKB-KW
- toxin activity Source: UniProtKB-KW
Keywordsi
Molecular function | Acetylcholine receptor inhibiting toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin |
Names & Taxonomyi
Protein namesi | Recommended name: Alpha-conotoxin LsIA1 Publication |
Organismi | Conus limpusi (Cone snail) |
Taxonomic identifieri | 1967283 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Spiralia › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Neogastropoda › Conoidea › Conidae › Conus › Eremiconus |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Other locations
- host cell postsynaptic membrane Source: UniProtKB-KW
Keywords - Cellular componenti
SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1 – 2 | Missing : 9-fold and 4.4-fold decrease in ability to inhibit alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-7/CHRNA7 nAChR subunits, respectively. 1 Publication | 2 | |
Mutagenesisi | 1 | Missing : 5.5-fold and 2.3-fold decrease in potency at alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-7/CHRNA7 nAChR subunits, respectively. 1 Publication | 1 | |
Mutagenesisi | 5 | S → AS: 160-fold decrease in ability to inhibit alpha-7/CHRNA7 nAChR subunit. 1 Publication | 1 | |
Mutagenesisi | 5 | S → R: No change in ability to inhibit alpha-7/CHRNA7 nAChR subunit. 1 Publication | 1 | |
Mutagenesisi | 6 | N → RN: 26-fold decrease in ability to inhibit alpha-7/CHRNA7 nAChR subunit. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
PeptideiPRO_0000439831 | 1 – 17 | Alpha-conotoxin LsIA1 PublicationAdd BLAST | 17 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 3 ↔ 9 | 1 Publication | ||
Disulfide bondi | 4 ↔ 17 | 1 Publication | ||
Modified residuei | 17 | Cysteine amide1 Publication | 1 |
Post-translational modificationi
Amidation at Cys-17 plays a critical role, since a C-terminally carboxylated analog is 3-fold less potent at the alpha-7/CHRNA7 nAChR subtype and 3-fold more potent at the alpha-3-beta-2/CHRNA3-CHRNB2 subtype.1 Publication
Keywords - PTMi
Amidation, Disulfide bondExpressioni
Tissue specificityi
Expressed by the venom duct.1 Publication
Structurei
3D structure databases
AlphaFoldDBi | P0DL68 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 5 – 7 | Ser-Xaa-Pro motif, crucial for potent interaction with nAChRBy similarity | 3 |
Domaini
The cysteine framework is I (CC-C-C). Alpha4/7 pattern.Curated
Sequence similaritiesi
Belongs to the conotoxin A superfamily.Curated
Family and domain databases
InterProi | View protein in InterPro IPR009958, Conotoxin_a-typ IPR018072, Conotoxin_a-typ_CS |
Pfami | View protein in Pfam PF07365, Toxin_8, 1 hit |
i Sequence
Sequence statusi: Complete.
Mass spectrometryi
Molecular mass is 1746.6 Da. Determined by MALDI. 1 Publication
Cross-referencesi
3D structure databases
AlphaFoldDBi | P0DL68 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Family and domain databases
InterProi | View protein in InterPro IPR009958, Conotoxin_a-typ IPR018072, Conotoxin_a-typ_CS |
Pfami | View protein in Pfam PF07365, Toxin_8, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CA1A_CONLM | |
Accessioni | P0DL68Primary (citable) accession number: P0DL68 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 10, 2017 |
Last sequence update: | May 10, 2017 | |
Last modified: | May 25, 2022 | |
This is version 12 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Animal Toxin Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencingDocuments
- SIMILARITY comments
Index of protein domains and families