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Protein

Mu-conotoxin KIIIB

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

Functioni

Mu-conotoxin KIIIA-P1: mu-conotoxins block voltage-gated sodium channels (Nav). This toxin potently blocks Nav1.2/SCN2A and Nav1.4/SCN4A (PubMed:17724025, PubMed:19221510, PubMed:21781281, PubMed:21709136, PubMed:25658507). It also moderately blocks Nav1.1/SCN1A, mNav1.6/SCN8A, and Nav1.7/SCN9A (PubMed:17724025, PubMed:21781281, PubMed:21709136, PubMed:21652775, PubMed:23146020, PubMed:25658507). It also shows a very low activity on Nav1.3/SCN3A (PubMed:17724025, PubMed:21781281). This toxin binds a microsite within the pore different from the tetrodotoxin binding site 1 (tested on Nav1.2) (PubMed:19221510). The block is partial, with a residual current that can be completely blocked by TTX (PubMed:19221510). The toxin probably docks at a more superficial site in the outer vestibule of the channel than does TTX (PubMed:19221510). On rNav1.2/SCN2A, it produces a block that is only partially reversible. The block of Nav1.7 is modified when beta-subunits are coexpressed with the alpha subunit (PubMed:23146020). 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) (PubMed:23146020).9 Publications
Mu-conotoxin KIIIA-P2: This toxin potently blocks Nav1.2/SCN2A (Kd=230 nM) and Nav1.4/SCN4A (Kd=830 nM). It also moderately blocks Nav1.7/SCN9A (Kd=1.57 µM). In addition, this toxin may also inhibit other sodium channels, as does Mu-conotoxin KIIIA-P1.1 Publication
Mu-conotoxin KIIIB-P1: This toxin potently blocks Nav1.2/SCN2A (Kd=470 nM). In addition, this toxin may also inhibit other sodium channels, as does Mu-conotoxin KIIIA-P1.1 Publication
Mu-conotoxin KIIIB-P2: This toxin potently blocks Nav1.2/SCN2A (Kd=26 nM). In addition, this toxin may also inhibit other sodium channels, as does Mu-conotoxin KIIIA-P1.1 Publication

Miscellaneous

Has no effect on hNav1.5/SCN5A (PubMed:17724025, PubMed:21781281, PubMed:25658507). Has no effect on hNav1.8/SCN10A (PubMed:21781281).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei11Key residue in the pharmacophore, alpha-helical region1 Publication1
Sitei12Key residue in the pharmacophore, alpha-helical region1 Publication1
Sitei14Key residue in the pharmacophore, alpha-helical region1 Publication1
Sitei15Key residue in the pharmacophore, alpha-helical region1 Publication1
Sitei16Key residue in the pharmacophore, alpha-helical region1 Publication1
Sitei18Key residue in the pharmacophore1 Publication1

GO - Molecular functioni

Keywordsi

Molecular functionIon channel impairing toxin, Neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin

Protein family/group databases

TCDBi8.B.28.1.4. the mu-conotoxin (mu-conotoxin) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Mu-conotoxin KIIIB1 Publication
Cleaved into the following chain:
Mu-conotoxin KIIIA1 Publication
OrganismiConus kinoshitai (Kinoshita's cone)
Taxonomic identifieri376876 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConusAfonsoconus

Organism-specific databases

ConoServeri1694. KIIIA precursor.

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; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi5C → A: Structure similar to wild-type toxin, even with this disulfide bond deletion. 1 Publication1
Mutagenesisi11K → A: Decrease in ability to block Nav1.3, Nav1.4, Nav1.6 and Nav1.7, but not Nav1.2. 21-fold decrease in binding affinity for Nav1.2. 3 Publications1
Mutagenesisi12W → A: Decrease in ability to block both Nav1.2 and Nav1.4. Decrease in binding affinity for Nav1.2, Nav1.4, and Nav1.7. 2 Publications1
Mutagenesisi12W → E: 200-fold decrease in ability to block Nav1.4. Block of Nav1.2 is completely reversible. 2 Publications1
Mutagenesisi12W → Q: 70-fold decrease in ability to block Nav1.4. Block of Nav1.2 is completely reversible. 2 Publications1
Mutagenesisi12W → R: 40-fold decrease in ability to block Nav1.4. Block of Nav1.2 is completely reversible. 2 Publications1
Mutagenesisi13C → A: Structure similar to wild-type toxin, even with this disulfide bond deletion. 1 Publication1
Mutagenesisi14R → A: Decrease in ability to block both Nav1.4 and Nav1.2, and decrease in binding affinity for Nav1.2, Nav1.4, and Nav1.7. 2 Publications1
Mutagenesisi15D → A: Decrease in ability to inhibit both Nav1.4 and Nav1.2. 1 Publication1
Mutagenesisi16H → A: Decrease in ability to inhibit both Nav1.4 and Nav1.2, and potently decreases the binding affinity for Nav1.2, Nav1.4, and Nav1.7. 2 Publications1
Mutagenesisi18R → A: Decrease in ability to inhibit both Nav1.4 and Nav1.2, and the binding affinity for Nav1.2, Nav1.4, and Nav1.7. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_0000442339‹1 – 21 Publication›2
PeptideiPRO_00004423403 – 20Mu-conotoxin KIIIB1 PublicationAdd BLAST18
PeptideiPRO_00002326625 – 20Mu-conotoxin KIIIA1 PublicationAdd BLAST16

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi5 ↔ 20in KIIIA-P2 and KIIIB-P1; alternate1 Publication
Disulfide bondi5 ↔ 19in KIIIA-P1 and KIIIB-P2; alternate1 PublicationImported
Disulfide bondi6 ↔ 13in KIIIA-P1, KIIIA-P2, KIIIB-P1 and KIIIB-P21 PublicationImported
Disulfide bondi8 ↔ 20in KIIIA-P1 and KIIIB-P2; alternate1 PublicationImported
Disulfide bondi8 ↔ 19in KIIIA-P2 and KIIIB-P1; alternate1 Publication
Modified residuei20Cysteine amide1 Publication1

Post-translational modificationi

PubMed:23167564 presents recalculated solution structures for mu-KIIIA-P1 with a new disulfide connectivity (C1-C5, C2-C4, C3-C6). This connectivity differs from that proposed in PubMed:19170536 (C1-C4, C2-C5, C3-C6).1 Publication

Keywords - PTMi

Amidation, Cleavage on pair of basic residues, Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom duct.1 Publication

Interactioni

Subunit structurei

Monomer.1 Publication

Structurei

Secondary structure

122
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi11 – 16Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LXGNMR-A5-20[»]
SMRiP0C195.
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.Curated

Sequence similaritiesi

Belongs to the conotoxin M superfamily.Curated

Sequencei

Sequence statusi: Fragment.

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

P0C195-1 [UniParc]FASTAAdd to basket

« Hide

        10         20 
KRNGCCNCSS KWCRDHSRCC GR
Length:22
Mass (Da):2,560
Last modified:November 22, 2017 - v2
Checksum:i6FA5E01DA18BB629
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11 Publication1

Similar proteinsi

Entry informationi

Entry nameiCM3A_CONKI
AccessioniPrimary (citable) accession number: P0C195
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 18, 2006
Last sequence update: November 22, 2017
Last modified: February 28, 2018
This is version 39 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure