Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Alpha-conotoxin RgIA

Gene
N/A
Organism
Conus regius (Crown 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. This toxin specifically inhibits the alpha-9-alpha-10 (CHRNA9-CHRNA10) nAChR, with preference for rat receptors (PubMed:16445293, PubMed:21888386, PubMed:22774872, PubMed:25740413, PubMed:28223528, 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).10 Publications

Miscellaneous

The cis-[2,8]-dicarba analog is significantly more stable and less susceptible to proteolytic degradation than native RgIA.1 Publication
Replacement of Arg-28 by a Citrulline residue strongly increases the potency on human CHRNA9-CHRNA10 nAChR. Replacement of Tyr-29 by a monoido-Tyr (3-I-Y) residue very strongly increases the potency on human CHRNA9-CHRNA10 nAChR.1 Publication
The synthetic variant RgIA4 (S23T; R28Citrulline; Y29(3-I-Y); R30Q; R32Y) is very potent on human CHRNA9-CHRNA10 (IC50=1.5 nM) and the most selective among all other synthetic variants tested (IC50>10 µM on all receptors tested, and (IC50=1.8 µM) on alpha-7/CHRNA9 nAChR).1 Publication
This toxin shows a weak activity on alpha-7 nAChR (IC50=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>10 µM) (PubMed:16445293).2 Publications

Caution

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei24Key residue for potent inhibition of the rat CHRNA9-CHRNA10 nAChR1 Publication1
Sitei25Key residue for potent inhibition of the rat 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 rat CHRNA9-CHRNA10 nAChR1 Publication1
Sitei28Key residue for potent inhibition of the rat CHRNA9-CHRNA10 nAChR1 Publication1
Sitei30Binds to the Glu-221 of the rat nAChR CHRNA10 subunit1 Publication1

GO - Molecular functioni

Keywordsi

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

Secreted

Pathology & Biotechi

Pharmaceutical usei

The derivative RgIA4 (S23T; R28Citrulline; Y29(3-I-Y); R30Q; R32Y) is under preclinical studies by Kineta under the name KCP-400. It is tested to prevent chronic cancer chemotherapy-induced neuropathic pain.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi23S → A: 1.7-fold less potent to inhibit both rat CHRNA9-CHRNA10 and CHRNA7 nAChR. 1 Publication1
Mutagenesisi23S → T: Extremely important increase in potency on human CHRNA9-CHRNA10 nAChR. 1 Publication1
Mutagenesisi24D → E: 783-fold and 8.3-fold less potent to inhibit rat CHRNA9-CHRNA10 and CHRNA7 nAChR, respectively. 1 Publication1
Mutagenesisi25P → V: 480-fold and 5.8-fold less potent to inhibit rat CHRNA9-CHRNA10 and CHRNA7 nAChR, respectively. 1 Publication1
Mutagenesisi26R → K: 1523-fold and 14.2-fold less potent to inhibit rat CHRNA9-CHRNA10 and CHRNA7 nAChR, respectively. 1 Publication1
Mutagenesisi28R → A: 1511-fold less potent to inhibit the rat CHRNA9-CHRNA10 nAChR and 5.8-fold more potent to inhibit the rat CHRNA7 nAChR. 1 Publication1
Mutagenesisi28R → K: No significant change in potency on human CHRNA9-CHRNA10 nAChR. 1 Publication1
Mutagenesisi29Y → W: 1.3-fold less potent to inhibit the rat CHRNA9-CHRNA10 nAChR and 1.1-fold more potent to inhibit the rat CHRNA7 nAChR. 1 Publication1
Mutagenesisi29Y → W: Relatively important increase in potency on human CHRNA9-CHRNA10 nAChR. 1 Publication1
Mutagenesisi30R → Q: Extremely important increase in potency on human CHRNA9-CHRNA10 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
Mutagenesisi32R → K: No significant change in potency on human CHRNA9-CHRNA10 nAChR. 1 Publication1
Mutagenesisi32R → Q: No significant change in potency on human CHRNA9-CHRNA10 nAChR. 1 Publication1
Mutagenesisi32R → Y: Extremely important increase in potency on human CHRNA9-CHRNA10 nAChR. 1 Publication1
Mutagenesisi32Missing : With C-31 amidated, no change in potency to inhibit the rat CHRNA9-CHRNA10 nAChR and 2.8-fold more potent to inhibit the rat 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

Keywords - PTMi

Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom duct.Curated

Structurei

Secondary structure

132
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:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JUQNMR-A20-32[»]
2JURNMR-A20-32[»]
2JUSNMR-A20-32[»]
2JUTNMR-A20-32[»]
2MTONMR-A20-32[»]
2MTTNMR-A20-30[»]
SMRiP0C1D0
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0C1D0

Family & Domainsi

Domaini

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

Sequencei

Sequence statusi: Fragment.

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

P0C1D0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30 
SNKRKNAAML DMIAQHAIRG CCSDPRCRYR CR
Length:32
Mass (Da):3,725
Last modified:May 16, 2006 - v1
Checksum:i4EC5B132037316F7
GO

Experimental Info

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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: April 25, 2018
This is version 40 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Pharmaceutical

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health