P56636 · CA12_CONMA
- ProteinAlpha-conotoxin MII
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
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).
Miscellaneous
There are currently a number of patents describing the use of this peptide in therapeutic applications.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | host cell postsynaptic membrane | |
Molecular Function | acetylcholine receptor inhibitor activity | |
Molecular Function | ion channel regulator activity | |
Molecular Function | toxin activity |
Keywords
- Molecular function
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameAlpha-conotoxin MII
- Short namesAlpha-Ctx MII ; Alpha-MII
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Spiralia > Lophotrochozoa > Mollusca > Gastropoda > Caenogastropoda > Neogastropoda > Conoidea > Conidae > Conus > Pionoconus
Accessions
- Primary accessionP56636
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 49 | 4.5-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. | ||||
Sequence: G → A | ||||||
Mutagenesis | 52 | 4.9-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. | ||||
Sequence: S → A | ||||||
Mutagenesis | 53 | >2700-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. | ||||
Sequence: N → A | ||||||
Mutagenesis | 54 | 700-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. | ||||
Sequence: P → A | ||||||
Mutagenesis | 55 | 2.5-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. | ||||
Sequence: V → A | ||||||
Mutagenesis | 57 | 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. | ||||
Sequence: H → A | ||||||
Mutagenesis | 58 | 1.5-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. | ||||
Sequence: L → A | ||||||
Mutagenesis | 59 | 4.6-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. | ||||
Sequence: E → A | ||||||
Mutagenesis | 60 | About 2700-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. | ||||
Sequence: H → A | ||||||
Mutagenesis | 61 | 2.3-fold decrease in ability to inhibit alpha-3-beta-2 nAChR. | ||||
Sequence: S → A | ||||||
Mutagenesis | 62 | No change in ability to inhibit alpha-3-beta-2 nAChR. | ||||
Sequence: N → A | ||||||
Mutagenesis | 63 | 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. | ||||
Sequence: L → A |
PTM/Processing
Features
Showing features for signal, propeptide, peptide, disulfide bond, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-21 | |||||
Sequence: MGMRMMFTVFLLVVLATTVVS | ||||||
Propeptide | PRO_0000034881 | 22-48 | ||||
Sequence: FPSDRASDGRNAAANDKASDVITLALK | ||||||
Peptide | PRO_0000034882 | 49-64 | Alpha-conotoxin MII | |||
Sequence: GCCSNPVCHLEHSNLC | ||||||
Disulfide bond | 50↔56 | |||||
Sequence: CCSNPVC | ||||||
Disulfide bond | 51↔64 | |||||
Sequence: CSNPVCHLEHSNLC | ||||||
Modified residue | 64 | Cysteine amide | ||||
Sequence: C |
Keywords
- PTM
Expression
Tissue specificity
Expressed by the venom duct.
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 52-54 | Ser-Xaa-Pro motif, crucial for potent interaction with nAChR | ||||
Sequence: SNP |
Domain
The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
Sequence similarities
Belongs to the conotoxin A superfamily.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length68
- Mass (Da)7,357
- Last updated2006-09-05 v3
- ChecksumFBD9AB40E6F277DF
Mass Spectrometry
Keywords
- Technical term