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Entry version 45 (18 Sep 2019)
Sequence version 1 (16 May 2006)
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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

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

This toxin target two types of receptors, the nicotinic acetylcholine receptor (nAChR) and the G-protein-coupled receptor GABA(B). It 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 (Cav2.2) 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
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>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

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

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

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Alpha-conotoxin RgIA2 Publications
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiConus regius (Crown cone)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri101314 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaNeogastropodaConoideaConidaeConusStephanoconus

Organism-specific databases

ConoServer: Cone snail toxin database

More...
ConoServeri
593 RgIA precursor

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section describes the use of a protein as a pharmaceutical drug. It indicates the name of the drug, the name of the firm that commercializes it and explains in a few words in which context the drug is used. In some cases, drugs that are under development are also described.<p><a href='/help/pharmaceutical_use' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>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

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.<p><a href='/help/propep' target='_top'>More...</a></p>PropeptideiPRO_0000234829‹1 – 19By similarityAdd BLAST›19
<p>This subsection of the ‘PTM / Processing’ section describes the position and length of an active peptide in the mature protein.<p><a href='/help/peptide' target='_top'>More...</a></p>PeptideiPRO_000023483020 – 32Alpha-conotoxin RgIA9 PublicationsAdd BLAST13

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi21 ↔ 272 PublicationsImported
Disulfide bondi22 ↔ 312 PublicationsImported

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed by the venom duct.Curated

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

132
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P0C1D0

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P0C1D0

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the conotoxin A superfamily.Curated

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR018072 Conotoxin_a-typ_CS

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS60014 ALPHA_CONOTOXIN, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Fragment.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i4EC5B132037316F7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section is used for sequence fragments to indicate that the residue at the extremity of the sequence is not the actual terminal residue in the complete protein sequence.<p><a href='/help/non_ter' target='_top'>More...</a></p>Non-terminal residuei11 Publication1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
DQ239610 Genomic DNA Translation: ABB55879.1

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>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:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
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[»]
6HY7X-ray2.26B20-32[»]
SMRiP0C1D0
ModBaseiSearch...
PDBe-KBiSearch...

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

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiCA1A_CONRE
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P0C1D0
Secondary accession number(s): Q1WJB2
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 16, 2006
Last modified: September 18, 2019
This is version 45 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>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
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