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Protein

Alpha-conotoxin ArIA

Gene
N/A
Organism
Conus arenatus (Sand-dusted cone)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. ArIA acts as a competitive inhibitor and is 3-fold more potent on alpha-7 nAChRs (IC50=6 nM) than on alpha-3-beta-2 nAChR (IC50=18 nM).1 Publication
ArIB acts as a competitive inhibitor and is 33-fold more potent on alpha-7 nAChRs (IC50=1.8 nM) than on alpha-3-beta-2 nAChR (IC50=60.1 nM).1 Publication

Miscellaneous

The mutant ArIB[V30L,V35D] is a potent and selective competitive antagonist of rat and human alpha-7 nAChRs, making it an attractive probe for this receptor subtype.2 Publications

GO - Molecular functioni

Keywordsi

Molecular functionAcetylcholine receptor inhibiting toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-conotoxin ArIA1 Publication
Cleaved into the following chain:
Alpha-conotoxin ArIB1 Publication
OrganismiConus arenatus (Sand-dusted cone)
Taxonomic identifieri89451 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri2838 ArIA precursor
3450 Sequence 299 from Patent EP1852440
351 Sequence 300 from patent US 6797808

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi25 – 27NPA → RPP: 8.8-fold decrease in inhibition of alpha-7 and 2.5 increase in inhibition of alpha-3-beta-2 nAChR. 1 Publication3
Mutagenesisi30V → L: 3.4-fold and 1.5-fold increase in inhibition of alpha-7 and alpha-3-beta-2 nAChR (ArIB[V30L]). 5.1-fold increase in inhibition of alpha-7 and 1.2-fold decrease in inhibition of alpha-3-beta-2 nAChR; when associated with A-35 (ArIB[V30L,V35A]). 1.7-fold increase in inhibition of alpha-7 and complete loss of inhibition of alpha-3-beta-2 nAChR; when associated with D-35 (ArIB[V30L,V35D]). 1 Publication1
Mutagenesisi35V → A: 5.1-fold increase in inhibition of alpha-7 and 1.2-fold decrease in inhibition of alpha-3-beta-2 nAChR; when associated with L-30 (ArIB[V30L,V35A]). 1 Publication1
Mutagenesisi35V → D: 1.7-fold increase in inhibition of alpha-7 and complete loss of inhibition of alpha-3-beta-2 nAChR; when associated with L-30 (ArIB[V30L,V35D]). 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_0000363985‹1 – 17By similarityAdd BLAST›17
PeptideiPRO_000036398618 – 36Alpha-conotoxin ArIA1 PublicationAdd BLAST19
PeptideiPRO_000036398720 – 36Alpha-conotoxin ArIB1 PublicationAdd BLAST17

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi22 ↔ 281 Publication
Disulfide bondi23 ↔ 361 Publication
Modified residuei334-hydroxyproline; in ArIA1 Publication1

Keywords - PTMi

Disulfide bond, Hydroxylation

Expressioni

Tissue specificityi

Expressed by the venom duct.Curated

Structurei

3D structure databases

ProteinModelPortaliP0C8R2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

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

InterProiView protein in InterPro
IPR009958 Conotoxin_a-typ
IPR018072 Conotoxin_a-typ_CS
PfamiView protein in Pfam
PF07365 Toxin_8, 1 hit
PROSITEiView protein in PROSITE
PS60014 ALPHA_CONOTOXIN, 1 hit

Sequencei

Sequence statusi: Fragment.

Sequence processingi: The displayed sequence is further processed into a mature form.

P0C8R2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30 
SDGRNVAAKA FHRIGRTIRD ECCSNPACRV NNPHVCRRR
Length:39
Mass (Da):4,437
Last modified:February 10, 2009 - v1
Checksum:iF16F910269E507B6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11

Similar proteinsi

Entry informationi

Entry nameiCAIA_CONAE
AccessioniPrimary (citable) accession number: P0C8R2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 10, 2009
Last sequence update: February 10, 2009
Last modified: April 25, 2018
This is version 25 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

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