UniProtKB - P56636 (CA12_CONMA)
Alpha-conotoxin MII
Functioni
Alpha-conotoxins bind to the nicotinic acetylcholine receptors (nAChR) and inhibit them. This toxin blocks neuronal mammalian nAChRs (alpha-6/alpha-3-beta-2-beta-3 (0.39 nM) > alpha-3-beta-2/CHRNA3-CHRNB2 > alpha-3-beta-4/CHRNA3-CHRNB4 = alpha-4-beta-2/CHRNA4-CHRNB2) (PubMed:15005608, PubMed:20145249).
Also exhibits inhibition of D.melanogaster alpha-7/CHRNA7 nAChRs (PubMed:25466886).
In addition, inhibits alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) nAChR with a higher potency on human (IC50=1.49 nM) than on rat receptors (IC50=31.5 nM) (PubMed:33523678).
Its binding to alpha-3-beta-2/CHRNA3-CHRNB2 nAChR is prevented by alpha-conotoxin Lt1a, suggesting that the two toxins have overlapping binding sites (PubMed:20145249).
In addition, both toxins have distinct nAChR binding mode (PubMed:20145249).
In vivo, inhibits Ehrlich carcinoma growth and increase mouse survival (PubMed:32272633).
These effects are greatly enhanced when the toxin is applied with the non-selective cyclooxygenase inhibitor indomethacin (PubMed:32272633).
10 PublicationsMiscellaneous
GO - Molecular functioni
- acetylcholine receptor inhibitor activity Source: UniProtKB-KW
- ion channel regulator activity Source: UniProtKB-KW
- toxin activity Source: UniProtKB-KW
Keywordsi
Molecular function | Acetylcholine receptor inhibiting toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin |
Protein family/group databases
TCDBi | 8.B.32.1.1, the nicotinic acetylcholine receptor-targeting alpha-conotoxin (a-conotoxin) family |
Names & Taxonomyi
Protein namesi | Recommended name: Alpha-conotoxin MII1 PublicationShort name: Alpha-Ctx MII1 Publication Short name: Alpha-MII1 Publication |
Organismi | Conus magus (Magical cone) |
Taxonomic identifieri | 6492 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Spiralia › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Neogastropoda › Conoidea › Conidae › Conus › Pionoconus |
Organism-specific databases
ConoServeri | 8, MII precursor |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Other locations
- host cell postsynaptic membrane Source: UniProtKB-KW
Keywords - Cellular componenti
SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 49 | G → A: 4.5-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. 1 Publication | 1 | |
Mutagenesisi | 52 | S → A: 4.9-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. 1 Publication | 1 | |
Mutagenesisi | 53 | N → A: >2700-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. 1 Publication | 1 | |
Mutagenesisi | 54 | P → A: 700-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. 1 Publication | 1 | |
Mutagenesisi | 55 | V → A: 2.5-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. 1 Publication | 1 | |
Mutagenesisi | 57 | H → A: 2-fold and ~20-fold decrease in ability to inhibit alpha-6/alpha-3-beta-2-beta-3 and alpha-3-beta-2, respectively. In MII[H9A;L15A]; exhibits preferential loss of activity at alpha-3-beta-2 versus alpha-6/alpha-3-beta-2-beta-3 nAChR, making this analog the most selective alpha-6 ligand known. 2 Publications | 1 | |
Mutagenesisi | 58 | L → A: 1.5-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. 1 Publication | 1 | |
Mutagenesisi | 59 | E → A: 4.6-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. 1 Publication | 1 | |
Mutagenesisi | 60 | H → A: About 2700-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. 1 Publication | 1 | |
Mutagenesisi | 61 | S → A: 2.3-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. 1 Publication | 1 | |
Mutagenesisi | 62 | N → A: No change in ability to inhibit alpha-3-beta-2 nAChR. 1 Publication | 1 | |
Mutagenesisi | 63 | L → A: 2.4-fold and 15-fold decrease in ability to inhibit alpha-6/alpha-3-beta-2-beta-3 and alpha-3-beta-2, respectively. In MII[H9A;L15A]; exhibits preferential loss of activity at alpha-3-beta-2 versus alpha-6/alpha-3-beta-2-beta-3 nAChR, making this analog the most selective alpha-6 ligand thus far reported. 2 Publications | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | Sequence analysisAdd BLAST | 21 | |
PropeptideiPRO_0000034881 | 22 – 48 | 1 PublicationAdd BLAST | 27 | |
PeptideiPRO_0000034882 | 49 – 64 | Alpha-conotoxin MII1 PublicationAdd BLAST | 16 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 50 ↔ 56 | 3 PublicationsImported | ||
Disulfide bondi | 51 ↔ 64 | 3 PublicationsImported | ||
Modified residuei | 64 | Cysteine amide2 Publications | 1 |
Keywords - PTMi
Amidation, Disulfide bondExpressioni
Tissue specificityi
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P56636 |
SMRi | P56636 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P56636 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 52 – 54 | Ser-Xaa-Pro motif, crucial for potent interaction with nAChR1 Publication | 3 |
Domaini
Sequence similaritiesi
Keywords - Domaini
SignalFamily and domain databases
InterProi | View protein in InterPro IPR009958, Conotoxin_a-typ IPR018072, Conotoxin_a-typ_CS |
Pfami | View protein in Pfam PF07365, Toxin_8, 1 hit |
PROSITEi | View protein in PROSITE PS60014, ALPHA_CONOTOXIN, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MGMRMMFTVF LLVVLATTVV SFPSDRASDG RNAAANDKAS DVITLALKGC
60
CSNPVCHLEH SNLCGRRR
Mass spectrometryi
Sequence databases
PIRi | A59046 |
Similar proteinsi
Cross-referencesi
Sequence databases
PIRi | A59046 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1M2C | NMR | - | A | 49-64 | [»] | |
1MII | NMR | - | A | 49-64 | [»] | |
2AJW | NMR | - | A | 49-64 | [»] | |
2AK0 | NMR | - | A | 49-64 | [»] | |
AlphaFoldDBi | P56636 | |||||
SMRi | P56636 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein family/group databases
TCDBi | 8.B.32.1.1, the nicotinic acetylcholine receptor-targeting alpha-conotoxin (a-conotoxin) family |
Organism-specific databases
ConoServeri | 8, MII precursor |
Miscellaneous databases
EvolutionaryTracei | P56636 |
Family and domain databases
InterProi | View protein in InterPro IPR009958, Conotoxin_a-typ IPR018072, Conotoxin_a-typ_CS |
Pfami | View protein in Pfam PF07365, Toxin_8, 1 hit |
PROSITEi | View protein in PROSITE PS60014, ALPHA_CONOTOXIN, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CA12_CONMA | |
Accessioni | P56636Primary (citable) accession number: P56636 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
Last sequence update: | September 5, 2006 | |
Last modified: | May 25, 2022 | |
This is version 107 of the entry and version 3 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
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families