UniProtKB - X5IWS1 (O17J_CONGE)
Protein
Mu-conotoxin GVIIJ
Gene
N/A
Organism
Conus geographus (Geography cone) (Nubecula geographus)
Status
Functioni
Mu-conotoxins block voltage-gated sodium channels (Nav). This toxin (GVIIJ(SSG)) blocks Nav1.1/SCN1A (Kd=11 nM), Nav1.2/SCN2A (Kd=11 nM), Nav1.3/SCN3A (Kd=15 nM), Nav1.4/SCN4A (Kd=4.7 nM), Nav1.6/SCN8A (Kd=360 nM) and Nav1.7/SCN9A (Kd=41 nM) (PubMed:24497506, PubMed:26039939). It binds the channel at the newly described site 8, which is composed by two surfaces whose one contains a non-disulfide-bonded cysteine (which is free to covalently bind the toxin Cys-71) (PubMed:24497506). It is noteworthy that coexpression of subunits beta-2 or beta-4 (but not beta-1 or beta-3) protects rNav1.1-1.7 against block by the toxin, since these subunits (thanks to their extracellular domain) covalently bind to the key cysteine of the channel, thus preventing the covalent binding of the toxin (PubMed:24497506, PubMed:25632083).4 Publications
Miscellaneous
This toxin shows a very low affinity to Nav1.5/SCN5A (Kd=207 µM) and does not show activity on rNav1.8/SCN10A.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 59 | Functionally important residue, that binds to the site 8 of the channel1 Publication | 1 | |
Sitei | 61 | Functionally important residue, that binds to the site 8 of the channel1 Publication | 1 | |
Sitei | 63 | Functionally important residue, that binds to the site 8 of the channel1 Publication | 1 | |
Sitei | 71 | Functionally important residue, that binds to the site 8 of the channel (distinct surface that K-59; R-61 and Y-63)1 Publication | 1 |
GO - Molecular functioni
- ion channel inhibitor activity Source: InterPro
- toxin activity Source: UniProtKB-KW
Keywordsi
Molecular function | Ion channel impairing toxin, Toxin, Voltage-gated sodium channel impairing toxin |
Names & Taxonomyi
Protein namesi | Recommended name: Mu-conotoxin GVIIJ1 PublicationAlternative name(s): Conotoxin muO-GVIIJ1 Publication MuO'section sign'-GVIIJ1 Publication |
Organismi | Conus geographus (Geography cone) (Nubecula geographus) |
Taxonomic identifieri | 6491 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Neogastropoda › Conoidea › Conidae › Conus › Gastridium |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Keywords - Cellular componenti
SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 49 | W → A: 10-fold decrease of affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 52 | D → K: No change in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 53 | P → A: No change in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 56 | T → A: No change in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 59 | K → D: 280-fold decrease of affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 60 | L → A: Small decrease in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 61 | R → D: 133-fold decrease of affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 62 | L → A: No change in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 63 | Y → A: 53-fold decrease of affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 66 | S → A: Small decrease in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 68 | F → A: No change in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 70 | D → N: No change in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 72 | Y → A, D or R: No change or small decrease in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 73 | T → A: No change in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 74 | K → D: 13-fold decrease of affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 74 | K → G or F: No change in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 75 | T → A: Small decrease in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 77 | K → A: No change in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 78 | D → K: No change in affinity to Nav1.2/SCNA2. 1 Publication | 1 | |
Mutagenesisi | 79 | K → D: Small decrease in affinity to Nav1.2/SCNA2. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 22 | Sequence analysisAdd BLAST | 22 | |
PropeptideiPRO_0000438880 | 23 – 47 | 1 PublicationAdd BLAST | 25 | |
ChainiPRO_5004957961 | 48 – 82 | Mu-conotoxin GVIIJ1 PublicationAdd BLAST | 35 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 49 | 6'-bromotryptophan1 Publication | 1 | |
Disulfide bondi | 50 ↔ 65 | Combined sources2 Publications | ||
Modified residuei | 53 | 4-hydroxyproline1 Publication | 1 | |
Disulfide bondi | 57 ↔ 69 | Combined sources2 Publications | ||
Disulfide bondi | 64 ↔ 76 | Combined sources2 Publications | ||
Modified residuei | 71 | S-cysteinyl cysteine1 Publication | 1 |
Post-translational modificationi
Cys-71 is a key residue that tethers to the channel by covalent attachment, leading to nearly irreversible inhibition (k(off) very low) (PubMed:24497506, PubMed:26817840). In order to determine the solution structure without dimerization, this residue was mutated to Cys.2 Publications
Keywords - PTMi
Bromination, Disulfide bond, HydroxylationExpressioni
Tissue specificityi
Expressed by the venom duct.1 Publication
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2N8H | NMR | - | A | 48-82 | [»] | |
SMRi | X5IWS1 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Family & Domainsi
Domaini
The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.1 Publication
The cysteine framework is VI/VII (C-C-CC-C-C).Curated
Sequence similaritiesi
Belongs to the conotoxin O1 superfamily.Curated
Keywords - Domaini
Knottin, SignalFamily and domain databases
InterProi | View protein in InterPro IPR004214 Conotoxin |
Pfami | View protein in Pfam PF02950 Conotoxin, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
X5IWS1-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MKLTCVVIVA ALLLTACQLI TALDCGGTQK HRALRSTIKL SLLRQHRGWC
60 70 80
GDPGATCGKL RLYCCSGFCD CYTKTCKDKS SA
Sequence cautioni
The sequence BAO65619 differs from that shown. Reason: Erroneous termination at position 76. Translated as Cys.Curated
Mass spectrometryi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB910851 mRNA Translation: BAO65619.1 Sequence problems. |
Similar proteinsi
Cross-referencesi
Web resourcesi
Biological Magnetic Resonance Data Bank synthetic GVIIJ[C71S] |
Biological Magnetic Resonance Data Bank synthetic GVIIJ disulfide-linked with cysteamine |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB910851 mRNA Translation: BAO65619.1 Sequence problems. |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2N8H | NMR | - | A | 48-82 | [»] | |
SMRi | X5IWS1 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Protocols and materials databases
Structural Biology Knowledgebase | Search... |
Family and domain databases
InterProi | View protein in InterPro IPR004214 Conotoxin |
Pfami | View protein in Pfam PF02950 Conotoxin, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | O17J_CONGE | |
Accessioni | X5IWS1Primary (citable) accession number: X5IWS1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 15, 2017 |
Last sequence update: | February 15, 2017 | |
Last modified: | October 10, 2018 | |
This is version 20 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Animal Toxin Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencingDocuments
- SIMILARITY comments
Index of protein domains and families - PDB cross-references
Index of Protein Data Bank (PDB) cross-references