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UniProtKB - P0C8R2 (CA1A_CONAE)
Protein
Alpha-conotoxin ArIA
Gene
N/A
Organism
Conus arenatus (Sand-dusted cone)
Status
Functioni
Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin acts as a competitive inhibitor and is 3-fold more potent on alpha-7/CHRNA7 nAChRs (IC50=6 nM) than on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR (IC50=18 nM).
1 PublicationActs as a competitive inhibitor and is 33-fold more potent on alpha-7/CHRNA7 nAChRs (IC50=1.8 nM) than on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR (IC50=60.1 nM).
1 PublicationMiscellaneous
The mutant ArIB[V30L,V35D] is a potent and selective competitive antagonist of rat and human alpha-7/CHRNA7 nAChRs, making it an attractive probe for this receptor subtype.2 Publications
GO - Molecular functioni
- acetylcholine receptor inhibitor activity Source: UniProtKB-KW
- ion channel regulator activity Source: UniProtKB-KW
- toxin activity Source: UniProtKB-KW
Keywordsi
Molecular function | Acetylcholine receptor inhibiting toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin |
Names & Taxonomyi
Protein namesi | Recommended name: Alpha-conotoxin ArIA1 PublicationCleaved into the following chain: Alpha-conotoxin ArIB1 Publication |
Organismi | Conus arenatus (Sand-dusted cone) |
Taxonomic identifieri | 89451 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Spiralia › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Neogastropoda › Conoidea › Conidae › Conus › |
Organism-specific databases
ConoServeri | 2838, ArIA precursor 3450, Sequence 299 from Patent EP1852440 351, Sequence 300 from patent US 6797808 |
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 | 25 – 27 | NPA → RPP: 8.8-fold decrease in inhibition of alpha-7/CHRNA7 and 2.5 increase in inhibition of alpha-3-beta-2/CHRNA3-CHRNB2 nAChR. 1 Publication | 3 | |
Mutagenesisi | 30 | V → L: 3.4-fold and 1.5-fold increase in inhibition of alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNA2 nAChR (ArIB[V30L]). 5.1-fold increase in inhibition of alpha-7/CHRNA7 and 1.2-fold decrease in inhibition of alpha-3-beta-2/CHRNA3-CHRNB2 nAChR; when associated with A-35 (ArIB[V30L,V35A]). 1.7-fold increase in inhibition of alpha-7/CHRNA7 and complete loss of inhibition of alpha-3-beta-2/CHRNA3-CHRNB2 nAChR; when associated with D-35 (ArIB[V30L,V35D]). 1 Publication | 1 | |
Mutagenesisi | 35 | V → A: 5.1-fold increase in inhibition of alpha-7/CHRNA7 and 1.2-fold decrease in inhibition of alpha-3-beta-2/CHRNA3-CHRNB2 nAChR; when associated with L-30 (ArIB[V30L,V35A]). 1 Publication | 1 | |
Mutagenesisi | 35 | V → D: 1.7-fold increase in inhibition of alpha-7/CHRNA7 and complete loss of inhibition of alpha-3-beta-2/CHRNA3-CHRNB2 nAChR; when associated with L-30 (ArIB[V30L,V35D]). 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
PropeptideiPRO_0000363985 | ‹1 – 17 | By similarityAdd BLAST | ›17 | |
PeptideiPRO_0000363986 | 18 – 36 | Alpha-conotoxin ArIA1 PublicationAdd BLAST | 19 | |
PeptideiPRO_0000363987 | 20 – 36 | Alpha-conotoxin ArIB1 PublicationAdd BLAST | 17 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 22 ↔ 28 | 1 Publication | ||
Disulfide bondi | 23 ↔ 36 | 1 Publication | ||
Modified residuei | 33 | 4-hydroxyproline; in ArIA1 Publication | 1 |
Keywords - PTMi
Disulfide bond, HydroxylationExpressioni
Tissue specificityi
Expressed by the venom duct.1 Publication
Structurei
3D structure databases
AlphaFoldDBi | P0C8R2 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 24 – 26 | 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 |
PROSITEi | View protein in PROSITE PS60014, ALPHA_CONOTOXIN, 1 hit |
i Sequence
Sequence statusi: Fragment.
: The displayed sequence is further processed into a mature form. Sequence processingi
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Non-terminal residuei | 1 | 1 |
Similar proteinsi
Cross-referencesi
3D structure databases
AlphaFoldDBi | P0C8R2 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Organism-specific databases
ConoServeri | 2838, ArIA precursor 3450, Sequence 299 from Patent EP1852440 351, Sequence 300 from patent US 6797808 |
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 |
PROSITEi | View protein in PROSITE PS60014, ALPHA_CONOTOXIN, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CA1A_CONAE | |
Accessioni | P0C8R2Primary (citable) accession number: P0C8R2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 10, 2009 |
Last sequence update: | February 10, 2009 | |
Last modified: | May 25, 2022 | |
This is version 34 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Animal Toxin Annotation Program |