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Protein

Alpha-conotoxin RgIA

Gene
N/A
Organism
Conus regius (Crown cone)
Status
Reviewed-Annotation score: Annotation score: 5 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. 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

Sites

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

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 lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri593. RgIA precursor.

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

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

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.

Cross-referencesi

Sequence databases

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

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...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri593. RgIA precursor.

Miscellaneous databases

EvolutionaryTraceiP0C1D0.

Family and domain databases

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

Entry informationi

Entry nameiCXA1A_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: March 15, 2017
This is version 36 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

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

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

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.