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Protein

Mu-conotoxin KIIIA

Gene
N/A
Organism
Conus kinoshitai (Kinoshita's cone)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Mu-conotoxins block voltage-gated sodium channels (Nav). This toxin potently blocks rNav1.2/SCN2A and rNav1.4/SCN4A. It also moderately blocks rNav1.1/SCN1A, rNav1.3/SCN3A, rNav1.5/SCN5A, mNav1.6/SCN8A, and rNav1.7/SCN9A. On rNav1.2/SCN2A, it produces a block that is only partially reversible. The block of SCN9A is modified when beta-subunits are coexpressed with the alpha subunit. Hence, blocks of channels containing beta-1 and beta-3 subunits are more potent (compared to channels without beta subunits), whereas blocks of channels containing beta-2 and beta-4 subunits are less potent (compared to channels without beta subunits).7 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei7 – 71Key residue in the pharmacophore, alpha-helical region
Sitei8 – 81Key residue in the pharmacophore, alpha-helical region
Sitei10 – 101Key residue in the pharmacophore, alpha-helical region
Sitei11 – 111Key residue in the pharmacophore, alpha-helical region
Sitei12 – 121Key residue in the pharmacophore, alpha-helical region
Sitei14 – 141Key residue in the pharmacophore

Keywords - Molecular functioni

Ion channel impairing toxin, Neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Mu-conotoxin KIIIA
OrganismiConus kinoshitai (Kinoshita's cone)
Taxonomic identifieri376876 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri1694. KIIIA precursor.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1 – 11C → A: Structure similar to wild-type toxin, even with this disulfide bond deletion. 1 Publication
Mutagenesisi7 – 71K → A: Attenuates the activity against rNav1.4/SCN4A but not rNav1.2/SCN2A. 2 Publications
Mutagenesisi8 – 81W → A: Attenuates the activity against both rNav1.4/SCN4A and rNav1.2/SCN2A. Attenuates the binding affinity of rNav1.2/SCN2A, rNav1.4/SCN2A, and rNav1.7/SCN9A. 2 Publications
Mutagenesisi8 – 81W → E: 200-fold reduction of activity toward rNav1.4/SCN4A. Block of rNav1.2/SCN2A is completely reversible. 2 Publications
Mutagenesisi8 – 81W → Q: 70-fold reduction of activity toward rNav1.4/SCN4A. Block of rNav1.2/SCN2A is completely reversible. 2 Publications
Mutagenesisi8 – 81W → R: 40-fold reduction of activity toward rNav1.4/SCN4A. Block of rNav1.2/SCN2A is completely reversible. 2 Publications
Mutagenesisi9 – 91C → A: Structure similar to wild-type toxin, even with this disulfide bond deletion. 1 Publication
Mutagenesisi10 – 101R → A: Attenuates the activity against both rNav1.4/SCN4A and rNav1.2/SCN2A, and the binding affinity of rNav1.2/SCN2A, rNav1.4/SCN4A, and rNav1.7/SCN9A. 2 Publications
Mutagenesisi11 – 111D → A: Attenuates the activity against both rNav1.4/SCN4A and rNav1.2/SCN2A. 1 Publication
Mutagenesisi12 – 121H → A: Attenuates the activity against both rNav1.4/SCN4A and rNav1.2/SCN2A, and potently decreases the binding affinity of rNav1.2/SCN2A, rNav1.4/SCN4A, and rNav1.7/SCN9A. 2 Publications
Mutagenesisi14 – 141R → A: Attenuates the activity against both rNav1.4/SCN4A and rNav1.2/SCN2A, and the binding affinity of rNav1.2/SCN2A, rNav1.4/SCN4A, and rNav1.7/SCN9A. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Peptidei1 – 1616Mu-conotoxin KIIIAPRO_0000232662Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi1 ↔ 91 Publication
Disulfide bondi2 ↔ 151 Publication
Disulfide bondi4 ↔ 161 Publication
Modified residuei16 – 161Cysteine amide

Keywords - PTMi

Amidation, Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom duct.

Interactioni

Subunit structurei

Monomer.1 Publication

Structurei

Secondary structure

1
18
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi7 – 126Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LXGNMR-A1-16[»]
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The cysteine framework is III (CC-C-C-CC). Classified in the M-5 branch, since 5 residues stand between the fourth and the fifth cysteine residues.

Sequence similaritiesi

Belongs to the conotoxin M superfamily.Curated

Sequencei

Sequence statusi: Complete.

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

P0C195-1 [UniParc]FASTAAdd to basket

« Hide

        10 
CCNCSSKWCR DHSRCCGR
Length:18
Mass (Da):2,104
Last modified:April 18, 2006 - v1
Checksum:i6FA593BD458C3C39
GO

Cross-referencesi

Web resourcesi

Biological Magnetic Resonance Data Bank

Mu-conotoxin KIIIA entry

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LXGNMR-A1-16[»]
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri1694. KIIIA precursor.

Family and domain databases

ProtoNetiSearch...

Entry informationi

Entry nameiCM3A_CONKI
AccessioniPrimary (citable) accession number: P0C195
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 18, 2006
Last sequence update: April 18, 2006
Last modified: January 7, 2015
This is version 31 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

Has no effect on hNav1.5/SCN5A and hNav1.8/SCN10A.1 Publication

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.