Alpha-conotoxin MII precursor - Conus magus (Magus cone)

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 > alpha-3-beta-4 = alpha-4-beta-2).5 Publications

Miscellaneous

There are currently a number of patents describing the use of this peptide in therapeutic applications.

GO - Molecular functionⁱ

acetylcholine receptor inhibitor activity Source: InterPro
toxin activity Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Acetylcholine receptor inhibiting toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin

Molecular function

Acetylcholine receptor inhibiting toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Alpha-conotoxin MII1 Publication Short name: Alpha-Ctx MII1 Publication Short name: Alpha-MII1 Publication
Organismⁱ	Conus magus (Magus cone) (Magician's cone snail)
Taxonomic identifierⁱ	6492 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Neogastropoda › Conoidea › Conidae › Conus › Pionoconus

Organism-specific databases

ConoServerⁱ	8 MII precursor

ConoServerⁱ

8 MII precursor

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Secreted

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	49	G → A: 4.5-fold decrease in inhibition of alpha-3/beta-2 nAChR. 1 Publication	1
Mutagenesisⁱ	52	S → A: 4.9-fold decrease in inhibition of alpha-3/beta-2 nAChR. 1 Publication	1
Mutagenesisⁱ	53	N → A: >2700-fold decrease in inhibition of alpha-3/beta-2 nAChR. 1 Publication	1
Mutagenesisⁱ	54	P → A: 700-fold decrease in inhibition of alpha-3/beta-2 nAChR. 1 Publication	1
Mutagenesisⁱ	55	V → A: 2.5-fold decrease in inhibition of 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 inhibition of alpha-3/beta-2 nAChR. 1 Publication	1
Mutagenesisⁱ	59	E → A: 4.6-fold decrease in inhibition of alpha-3/beta-2 nAChR. 1 Publication	1
Mutagenesisⁱ	60	H → A: About 2700-fold decrease in inhibition of alpha-3/beta-2 nAChR. 1 Publication	1
Mutagenesisⁱ	61	S → A: 2.3-fold decrease in inhibition of alpha-3/beta-2 nAChR. 1 Publication	1
Mutagenesisⁱ	62	N → A: No change in inhibition of 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	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	Length
Disulfide bondⁱ	50 ↔ 56	3 PublicationsImported
Disulfide bondⁱ	51 ↔ 64	3 PublicationsImported
Modified residueⁱ	64	Cysteine amide2 Publications	1

Keywords - PTMⁱ

Amidation, Disulfide bond

Expressionⁱ

Tissue specificityⁱ

Expressed by the venom duct.1 Publication

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Turnⁱ	50 – 52	Combined sources	3
Helixⁱ	54 – 59	Combined sources	6
Helixⁱ	61 – 63	Combined sources	3

Show more details

3D structure databases

ProteinModelPortalⁱ	P56636
SMRⁱ	P56636
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P56636

EvolutionaryTraceⁱ

P56636

Family & Domainsⁱ

Domainⁱ

The cysteine framework is I (CC-C-C). Alpha4/7 pattern.Curated

Sequence similaritiesⁱ

Belongs to the conotoxin A superfamily.Curated

Keywords - Domainⁱ

Signal

Family and domain databases

InterProⁱ	View protein in InterPro IPR009958 Conotoxin_a-typ IPR018072 Conotoxin_a-typ_CS
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF07365 Toxin_8, 1 hit
PROSITEⁱ	View protein in PROSITE PS60014 ALPHA_CONOTOXIN, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

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

P56636-1 [UniParc]FASTA Add to basket

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        10         20         30         40         50
MGMRMMFTVF LLVVLATTVV SFPSDRASDG RNAAANDKAS DVITLALKGC 
        60 
CSNPVCHLEH SNLCGRRR

Length:68

Mass (Da):7,357

Last modified:September 5, 2006 - v3

Checksum:ⁱFBD9AB40E6F277DF

GO

Mass spectrometryⁱ

Molecular mass is 1710.6 Da from positions 49 - 64. Determined by LSI. 1 Publication

Sequence databases

PIRⁱ	A59046

PIRⁱ

A59046

Protein	Similar proteins		Species	Score	Length	Source
P56636	Alpha-conotoxin-like Sm1.3		CONSE		63	UniRef90_P56636
A-conotoxin (Fragment)		Conus sp. n. 1 NP-2014		68
Conopeptide (Fragment)		CONLV		39

Protein	Similar proteins		Species	Score	Length	Source
P56636	Alpha-conotoxin-like Sm1.3		CONSE		63	UniRef50_P56636
Alpha-conotoxin Pu14.1		CONPL		69
Alpha-conotoxin-like Ca1.2		CONCB		68
Alpha-conotoxin-like Mr1.3		CONMR		68
Alpha-conotoxin S1	)	CONST		64
+127

Cross-referencesⁱ

Sequence databases

PIRⁱ	A59046

PIRⁱ

A59046

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...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	[»]
ProteinModelPortalⁱ	P56636
SMRⁱ	P56636
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Organism-specific databases

ConoServerⁱ	8 MII precursor

ConoServerⁱ

8 MII precursor

Miscellaneous databases

EvolutionaryTraceⁱ	P56636

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
ProtoNetⁱ	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:	September 12, 2018
	This is version 94 of the entry and version 3 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Animal Toxin Annotation Program

UniProtKB

UniParc

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Annotation systems

Supporting data

UniProtKB - P56636 (CA12_CONMA)

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Alpha-conotoxin MII

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted

Extracellular region or secreted

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Family and domain databases

<p>This subsection of the ‘Sequence’ section reports information derived from mass spectrometry experiments done on the entire protein or on biologically active derived peptide(s).<p><a href='/help/mass_spectrometry' target='_top'>More...</a></p>Mass spectrometryi

Sequence databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protocols and materials databases

Organism-specific databases

Miscellaneous databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Mass spectrometryⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ