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Alpha-conotoxin RgIA

Conus regius (Crown cone)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli


Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin specifically inhibits the alpha-9-alpha-10 (CHRNA9-CHRNA10) nAChR (PubMed:16445293, PubMed:21888386, PubMed:22774872, PubMed:25740413, PubMed:18242183, PubMed:18295795). It interacts with the alpha-10+/alpha-9-interface of the receptor (PubMed:25740413). It shows a two order of magnitude species difference potency for the rat versus human alpha-9-alpha-10 nAChR, due to the Thr-86 located in the alpha-9 nAChR subunit (PubMed:22774872). This toxin also shows inhibition of high voltage-activated (HVA) calcium channels by acting on GABA(B) receptors (GABBR1 and GABBR2) (PubMed:18945902, PubMed:21888386). In vivo, this toxin produces an acute antinociceptive effect in peripheral nerve-injured rats, which may be related to the inhibition of immune cell buildup at the site of nerve injury (PubMed:17101979). In addition, when intramuscularly injected into rats following chronic constriction injury of the sciatic nerve, this toxin protects peripheral nervous tissues as well as prevents central maladaptive plasticity by inhibiting glial cell activation (PubMed:25008370).9 Publications


This toxin shows a weak activity on alpha-7 nAChR (IC50 is 3310-4660 nM) (PubMed:16445293, PubMed:18295795). It also shows a very weak activity on alpha-2-beta-2, alpha-2-beta-4, alpha-3-beta-4, alpha-3-beta-2, alpha-4-beta-2, alpha-4-beta-4 and alpha-6/alpha-3-beta-2-beta-3 nAChRs (IC50 are > 10000 nM) (PubMed:16445293).2 Publications


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei24Key residue for potent inhibition of the CHRNA9-CHRNA10 nAChr1 Publication1
Sitei25Key residue for potent inhibition of the CHRNA9-CHRNA10 nAChR1 Publication1
Sitei26Binds to the Pro-224 and Asp-225 of the rat nAChR CHRNA10 subunit1 Publication1
Sitei26Key residue for potent inhibition of the CHRNA9-CHRNA10 nAChR1 Publication1
Sitei28Key residue for potent inhibition of the CHRNA9-CHRNA10 nAChR1 Publication1
Sitei30Binds to the Glu-221 of the rat nAChR CHRNA10 subunit1 Publication1

GO - Molecular functioni


Molecular functionAcetylcholine receptor inhibiting toxin, G-protein coupled receptor impairing toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-conotoxin RgIA2 Publications
OrganismiConus regius (Crown cone)
Taxonomic identifieri101314 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConusStephanoconus

Organism-specific databases

ConoServeri593. RgIA precursor.

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


Pathology & Biotechi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi23S → A: 1.7-fold less potent to inhibit both CHRNA9-CHRNA10 and CHRNA7 nAChR. 1 Publication1
Mutagenesisi24D → E: 783-fold and 8.3-fold less potent to inhibit CHRNA9-CHRNA10 and CHRNA7 nAChR, respectively. 1 Publication1
Mutagenesisi25P → V: 480-fold and 5.8-fold less potent to inhibit CHRNA9-CHRNA10 and CHRNA7 nAChR, respectively. 1 Publication1
Mutagenesisi26R → K: 1523-fold and 14.2-fold less potent to inhibit CHRNA9-CHRNA10 and CHRNA7 nAChR, respectively. 1 Publication1
Mutagenesisi28R → A: 1511-fold less potent to inhibit the CHRNA9-CHRNA10 nAChR and 5.8-fold more potent to inhibit the CHRNA7 nAChR. 1 Publication1
Mutagenesisi29Y → W: 1.3-fold less potent to inhibit the CHRNA9-CHRNA10 nAChR and 1.1-fold more potent to inhibit the CHRNA7 nAChR. 1 Publication1
Mutagenesisi32R → GGAAGAG: With cyclization, improvement in the stability, small increase in inhibition of human CHRNA9/rat CHRNA10 nAChR and no change in GABA(B)/N-type calicum channels (cRgIA-7). 1 Publication1
Mutagenesisi32Missing : With C-31 amidated, no change in potency to inhibit the CHRNA9-CHRNA10 nAChR and 2.8-fold more potent to inhibit the CHRNA7 nAChR. Similar inhibition of human CHRNA9/rat CHRNA10 nAChR and increase in inhibition of GABA(B)/N-type calicum channels (RgIA[delR]). 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_0000234829‹1 – 19By similarityAdd BLAST›19
PeptideiPRO_000023483020 – 32Alpha-conotoxin RgIA9 PublicationsAdd BLAST13

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi21 ↔ 272 PublicationsImported
Disulfide bondi22 ↔ 312 PublicationsImported

Post-translational modificationi

The disulfide bond CysI-CysIII is important for alpha-9-alpha-10 subtype inhibition, whereas the bond CysII-CysIV contributes to GABA(B) modulation.1 Publication
The cis-[2,8]-dicarba analog is significantly more stable and less susceptible to proteolytic degradation than native RgIA.1 Publication

Keywords - PTMi

Disulfide bond


Tissue specificityi

Expressed by the venom duct.Curated


Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi22 – 24Combined sources3
Helixi25 – 27Combined sources3
Turni29 – 31Combined sources3

3D structure databases

Select the link destinations:
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum

Miscellaneous databases


Family & Domainsi


The cysteine framework is I (CC-C-C). Alpha4/3 pattern.Curated

Sequence similaritiesi

Belongs to the conotoxin A superfamily.Curated

Family and domain databases

InterProiView protein in InterPro
IPR018072. Conotoxin_a-typ_CS.
PROSITEiView protein in PROSITE
PS60014. ALPHA_CONOTOXIN. 1 hit.


Sequence statusi: Fragment.

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

P0C1D0-1 [UniParc]FASTAAdd to basket

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        10         20         30 
Mass (Da):3,725
Last modified:May 16, 2006 - v1

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11 Publication1

Sequence databases

Select the link destinations:
Links Updated
DQ239610 Genomic DNA. Translation: ABB55879.1.

Similar proteinsi

Entry informationi

Entry nameiCA1A_CONRE
AccessioniPrimary (citable) accession number: P0C1D0
Secondary accession number(s): Q1WJB2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 16, 2006
Last modified: January 31, 2018
This is version 39 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program



Has the same mature sequence than Reg1e (AC P85011). RgIA could therefore be the precursor of Reg1e, except that RgIA does not have the C-terminal Gly residue required for C-terminal amidation of Reg1e.Curated

Keywords - Technical termi