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UniProt functional annotation for X5IWS1 | ||
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| UniProt code: X5IWS1. |
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| Organism: | |
Conus geographus (Geography cone) (Nubecula geographus). |
| Taxonomy: | |
Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda; Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Gastridium. |
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| Function: | |
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). {ECO:0000269|PubMed:24497506, ECO:0000269|PubMed:25632083, ECO:0000269|PubMed:26039939, ECO:0000269|PubMed:26817840}. |
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| Subcellular location: | |
Secreted {ECO:0000269|PubMed:24662800}. |
| Tissue specificity: | |
Expressed by the venom duct. {ECO:0000305|PubMed:24662800}. |
| Domain: | |
The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. {ECO:0000269|PubMed:26817840}. |
| Domain: | |
The cysteine framework is VI/VII (C-C-CC-C-C). {ECO:0000305}. |
| Ptm: | |
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. {ECO:0000269|PubMed:24497506, ECO:0000269|PubMed:26817840}. |
| Mass spectrometry: | |
Mass=3934.49; Method=MALDI; Evidence={ECO:0000269|PubMed:24497506}; |
| Miscellaneous: | |
This toxin shows a very low affinity to Nav1.5/SCN5A (Kd=207 uM) and does not show activity on rNav1.8/SCN10A. {ECO:0000269|PubMed:24497506}. |
| Similarity: | |
Belongs to the conotoxin O1 superfamily. {ECO:0000305}. |
| Sequence caution: | |
Sequence=BAO65619.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; |
Annotations taken from UniProtKB at the EBI.