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Protein

Alpha-conotoxin ArIA

Gene
N/A
Organism
Conus arenatus (Sand-dusted cone)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-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

GO - Biological processi

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

  • Secreted By similarity

GO - Cellular componenti

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

Cross-referencesi

3D structure databases

ProteinModelPortaliP0C8R2.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

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

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.
ProtoNetiSearch...

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: May 10, 2017
This is version 23 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.