P50983 (CA1_CONIM) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Alpha-conotoxin ImI Short name=Alpha-CTx ImI
Organism	Conus imperialis (Imperial cone)
Taxonomic identifier	35631 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Hypsogastropoda › Neogastropoda › Conoidea › Conidae › Conus

Protein attributes

Sequence length	17 AA.
Sequence status	Fragment.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian neuronal nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Has no effect on nAChRs composed of alpha-2/beta-2, alpha-3/beta-2, alpha-4/beta-2, alpha-2/beta-4, alpha-3/beta-4, or alpha-4/beta-4 subunits. Acts voltage-independently. Is highly active against the neuromuscular receptor in frog. Ref.2
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom duct.
Domain	The cysteine framework is I (CC-C-C).
Post-translational modification	Not hydroxylated; hydroxylation, on a synthetic hydroxylated ImI, improves its folding but impairs its activity against target receptors.
Sequence similarities	Belongs to the conotoxin A superfamily.

Ontologies

Keywords
Cellular component	Secreted
Molecular function	Acetylcholine receptor inhibiting toxin Neurotoxin Postsynaptic neurotoxin Toxin
PTM	Amidation Cleavage on pair of basic residues Disulfide bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Cellular_component	other organism postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	acetylcholine receptor inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

‹1 – 4

›4

PRO_0000273426

Peptide

5 – 16

12

Alpha-conotoxin ImI Ref.2

PRO_0000034877

Amino acid modifications

Modified residue

16

1

Cysteine amide

Disulfide bond

6 ↔ 12

Ref.2 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10

Disulfide bond

7 ↔ 16

Ref.2 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10

Experimental info

Mutagenesis

9

1

D → L: Reduction of toxicity. Ref.10

Mutagenesis

11

1

R → L: Reduction of toxicity. Ref.10

Mutagenesis

15

1

R → E: No loss of activity. Ref.10

Non-terminal residue

1

1

Secondary structure

1

.

.

.

.

.

.

17

Helix Strand Turn

Details...

Helix

6 – 8

3

Turn

10 – 12

3

Helix

13 – 15

3

Sequences

	Sequence		Length	Mass (Da)
	P50983 [UniParc]. Last modified January 16, 2004. Version 2. Checksum: 9590D9CEA50279CF	FASTA	17	1,938
	10 IVRRGCCSDP RCAWRCG

References

[1]	"Alpha-conotoxins ImI and ImII: similar alpha 7 nicotinic receptor antagonists act at different sites." Ellison M.A., McIntosh J.M., Olivera B.M. J. Biol. Chem. 278:757-764(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SYNTHESIS OF 5-16. Tissue: Venom duct.
[2]	"A nicotinic acetylcholine receptor ligand of unique specificity, alpha-conotoxin ImI." McIntosh J.M., Yoshikami D., Mahe E., Nielsen D.B., Rivier J.E., Gray W.R., Olivera B.M. J. Biol. Chem. 269:16733-16739(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 5-16, FUNCTION, SYNTHESIS OF 5-16, DISULFIDE BONDS. Tissue: Venom.
[3]	"Alpha-conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: preferential inhibition of homomeric alpha 7 and alpha 9 receptors." Johnson D.S., Martinez J., Elgoyhen A.B., Heinemann S.F., McIntosh J.M. Mol. Pharmacol. 48:194-199(1995) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[4]	"Role of hydroxyprolines in the in vitro oxidative folding and biological activity of conotoxins." Lopez-Vera E., Walewska A., Skalicky J.J., Olivera B.M., Bulaj G. Biochemistry 47:1741-1751(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SYNTHESIS OF 5-16, ROLE OF HYDROXYLATION.
[5]	"NMR solution structure of alpha-conotoxin ImI and comparison to other conotoxins specific for neuronal nicotinic acetylcholine receptors." Rogers J.P., Luginbuehl P., Shen G.S., McCabe R.T., Stevens R.C., Wemmer D.E. Biochemistry 38:3874-3882(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 5-16, DISULFIDE BONDS.
[6]	"Solution structure of alpha-conotoxin ImI determined by two-dimensional NMR spectroscopy." Gouda H., Hirono S. Biochim. Biophys. Acta 1431:384-394(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 5-16, DISULFIDE BONDS.
[7]	"NMR spatial structure of alpha-conotoxin ImI reveals a common scaffold in snail and snake toxins recognizing neuronal nicotinic acetylcholine receptors." Maslennikov I.V., Shenkarev Z.O., Zhmak M.N., Ivanov V.T., Methfessel C., Tsetlin V.I., Arseniev A.S. FEBS Lett. 444:275-280(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 5-16, DISULFIDE BONDS.
[8]	"Minimal conformation of the alpha-conotoxin ImI for the alpha7 neuronal nicotinic acetylcholine receptor recognition: correlated CD, NMR and binding studies." Lamthanh H., Jegou-Matheron C., Servent D., Menez A., Lancelin J.-M. FEBS Lett. 454:293-298(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 5-16, DISULFIDE BONDS.
[9]	"Solution structure of alpha-conotoxin ImI by 1H nuclear magnetic resonance." Gehrmann J., Daly N.L., Alewood P.F., Craik D.J. J. Med. Chem. 42:2364-2372(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 5-16, DISULFIDE BONDS.
[10]	"Structure-activity relationships in a peptidic alpha7 nicotinic acetylcholine receptor antagonist." Rogers J.P., Luginbuhl P., Pemberton K., Harty P., Wemmer D.E., Stevens R.C. J. Mol. Biol. 304:911-926(2000) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASP-9; ARG-11 AND ARG-15, STRUCTURE BY NMR OF 5-16 OF THESE THREE MUTANTS, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY159318 Genomic DNA. Translation: AAN78128.1.

PIR

A53709.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CNL	NMR	-	A	5-16	[»]
1E74	NMR	-	A	5-14	[»]
1E75	NMR	-	A	5-16	[»]
1E76	NMR	-	A	5-16	[»]
1G2G	NMR	-	A	5-16	[»]
1IM1	NMR	-	A	5-16	[»]
1IMI	NMR	-	A	5-16	[»]
2BC7	NMR	-	A	7-16	[»]
2BC8	NMR	-	A	8-15	[»]
2BYP	X-ray	2.07	F/G/H/I/J	5-16	[»]
2C9T	X-ray	2.25	K/M/O/P/Q/R/S/T	5-16	[»]

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ConoServer

93. ImI precursor.

Family and domain databases

InterPro

IPR018072. Conotoxin_a-typ_CS.
[Graphical view]

PROSITE

PS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P50983.

Entry information

Entry name

CA1_CONIM

Accession

Primary (citable) accession number: P50983
Secondary accession number(s): Q8I6R4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 16, 2004
Last modified:	May 1, 2013
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program