Alpha-conotoxin LvIA precursor - Conus lividus (Livid cone)

Functionⁱ

Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks alpha-3-beta-2/CHRNA3-CHRNB2 nAChR with high selectivity (IC₅₀=8.67 nM (on rat) and 17.5 (on human)) (PubMed:24398291). Has also weaker activity on alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) (IC₅₀=108 nM (on rat)), alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) (IC₅₀=121 nM (on rat)), alpha-3-beta-4 (CHRNA3-CHRNB4) (IC₅₀=148 nM (on rat)), and alpha-7/CHRNA7 nAChRs (IC₅₀=3000 nM (on rat)) (PubMed:24398291). When tested on mouse with hot-plate tests, this toxin significantly increases the base pain threshold and shows analgesic effects (PubMed:26742048).2 Publications

Miscellaneous

Does not block alpha-9-alpha-10/CHRNA9-CHRNA10, alpha-2-beta-2/CHRNA2-CHRNB2, alpha-2-beta-4/CHRNA2-CHRNB4, alpha-3-beta-4/CHRNA3-CHRNB4, alpha-4-beta-2/CHRNA4-CHRNB2, alpha-4-beta-4/CHRNA4-CHRNB4, alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3), alpha-6-beta-4/CHRNA6-CHRNB4, and alpha-1-beta-1-epsilon-delta/CHRNA1-CHRNB1-CHRNE-CHRND.2 Publications

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Siteⁱ	31	May play a crucial role for the selectivity for alpha-3-beta-2 nAChR1 Publication		1

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 LvIA2 Publications Short name: Alpha-CTx LvIA2 Publications
Organismⁱ	Conus lividus (Livid cone)
Taxonomic identifierⁱ	89426 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Neogastropoda › Conoidea › Conidae › Conus › Lividoconus

Keywords - Cellular componentⁱ

Secreted

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	29 – 30	NV → RA: Shows inhibition on alpha-3-beta-2 (IC(50)=3.3 nM), beta-3-alpha-6-beta-2-alpha-4-beta-2 (IC(50)=11.4 nM), alpha-6/alpha-3-beta-2-beta-3 (IC(50)=13.5 nM), alpha-4-beta-2 (IC(50)=195 nM), alpha-6/alpha-3-beta-4 (IC(50)=1000 nM) nAChRs. Does not inhibit alpha-3-beta-4, beta-4-alpha-3-beta-4-alpha-3-alpha-5, and alpha-4-beta-4 nAChRs. 1 Publication		2

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
PropeptideⁱPRO_0000430172	‹1 – 20	By similarityAdd BLAST		›20
PeptideⁱPRO_0000430173	21 – 36	Alpha-conotoxin LvIA1 PublicationAdd BLAST		16

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Disulfide bondⁱ	22 ↔ 28	Combined sources1 Publication
Disulfide bondⁱ	23 ↔ 36	Combined sources1 Publication
Modified residueⁱ	36	Cysteine amide1 Publication	1

Keywords - PTMⁱ

Amidation, Cleavage on pair of basic residues, Disulfide bond

Expressionⁱ

Tissue specificityⁱ

Expressed by the venom duct.Curated

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	22 – 24	Combined sources	3
Helixⁱ	26 – 31	Combined sources	6
Turnⁱ	33 – 35	Combined sources	3

Show more details

3D structure databases

SMRⁱ	L8BU87
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domainⁱ

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

Sequence similaritiesⁱ

Belongs to the conotoxin A superfamily.Curated

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: Fragment.

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

L8BU87-1 [UniParc]FASTA Add to basket

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        10         20         30 
FRGRDAAAKA SGLVGLTDRR GCCSHPACNV DHPEICG

Length:37

Mass (Da):3,841

Last modified:April 3, 2013 - v1

Checksum:ⁱB5501D068E48873C

GO

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Non-terminal residueⁱ	1			1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	HF566436 Genomic DNA Translation: CCP46959.1

Select the link destinations:
EMBLⁱ
GenBankⁱ
DDBJⁱ

Links Updated

HF566436 Genomic DNA Translation: CCP46959.1

Similar proteinsⁱ

50% Identity

Protein	Similar proteins		Species	Score	Length	Source
L8BU87	Alpha-conotoxin (Fragment)		CONLI		33	UniRef50_L8BU87
Alpha-conotoxin (Fragment)		Conus sanguinolentus		33
Alpha-conotoxin (Fragment)		CONDD		33
Alpha-conotoxin-like (Fragment)		CONTE		38
Alpha-conotoxin-like (Fragment)		CONDD		33
+1

Cross-referencesⁱ

Web resourcesⁱ

Biological Magnetic Resonance Data Bank

synthetic Alpha-conotoxin LvIA

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	HF566436 Genomic DNA Translation: CCP46959.1

Select the link destinations:
EMBLⁱ
GenBankⁱ
DDBJⁱ

Links Updated

HF566436 Genomic DNA Translation: CCP46959.1

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
	2MDQ	NMR	-	A	21-36	[»]
	5XGL	X-ray	3.44	C/E/F/H/J	21-36	[»]
SMRⁱ	L8BU87
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

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	CA1A_CONLI
Accessionⁱ	L8BU87Primary (citable) accession number: L8BU87
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	September 3, 2014
	Last sequence update:	April 3, 2013
	Last modified:	November 7, 2018
	This is version 21 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Animal Toxin Annotation Program

UniProtKB

UniParc

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Supporting data

UniProtKB - L8BU87 (CA1A_CONLI)

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Alpha-conotoxin LvIA

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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

Sites

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Extracellular region or secreted

Extracellular region or secreted

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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

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<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

Family and domain databases

Experimental Info

Sequence databases

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Sequence databases

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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

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ