P50982 (CA1_CONER) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Alpha-conotoxin EI
Organism	Conus ermineus (Atlantic fish-hunting cone)
Taxonomic identifier	55423 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Hypsogastropoda › Neogastropoda › Conoidea › Conidae › Conus

Protein attributes

Sequence length	62 AA.
Sequence status	Complete.
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. Blocks mammalian nAChR composed of alpha-1/gamma and alpha-1/delta subunits. Blocks central nervous system nAChR composed of alpha-4/beta-2 subunits and peripheral nervous system nAChR composed of alpha-3/beta-4 subunits. Low toxin concentrations potentiate currents in muscle nAChR composed of alpha-1/beta-1/gamma/delta subunits and central nervous system nAChR composed of alpha-4/beta-2 subunits, but not peripheral nervous system nAChR composed of alpha-3/beta-4 subunits. Ref.2 Ref.3
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom duct.
Domain	The cysteine framework is I (CC-C-C).
Sequence similarities	Belongs to the conotoxin A superfamily.
Mass spectrometry	Molecular mass is 2092.9 Da from positions 44 - 61. Determined by LSI. Ref.2

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Acetylcholine receptor inhibiting toxin Neurotoxin Postsynaptic neurotoxin Toxin
PTM	Amidation Disulfide bond Hydroxylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological_process	pathogenesis Inferred from direct assay PubMed 96062516. Source: UniProtKB
Cellular_component	extracellular region Inferred from direct assay PubMed 96062516. Source: UniProtKB other organism postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	acetylcholine receptor inhibitor activity Inferred from direct assay PubMed 96062516. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 16

16

Potential

Propeptide

17 – 43

27

PRO_0000392693

Peptide

44 – 61

18

Alpha-conotoxin EI Ref.2

PRO_0000044458

Amino acid modifications

Modified residue

46

1

4-hydroxyproline Ref.2 Ref.4

Modified residue

61

1

Cysteine amide Ref.2 Ref.4

Disulfide bond

47 ↔ 53

Ref.2 Ref.4

Disulfide bond

48 ↔ 61

Ref.2 Ref.4

Secondary structure

1

.

.

.

.

.

.

.

62

Helix Strand Turn

Details...

Helix

46 – 49

4

Helix

52 – 55

4

Helix

58 – 60

3

Sequences

	Sequence		Length	Mass (Da)
	P50982 [UniParc]. Last modified March 23, 2010. Version 2. Checksum: 7D3E9D3F46B52186	FASTA	62	6,637
	10 20 30 40 50 60 MFTVFLLVVL ATTVGSFTLD RASDGRDAAA NDKASDLIAL TARRDPCCYH PTCNMSNPQI CG

References

[1]	"Alpha conotoxin peptides." Olivera B.M., Layer R.T., Watkins M., Hillyard D.R., Mcintosh M.J., Jones R.M., Schoenfeld R. Patent number JP2003525582, 02-SEP-2003 Cited for: NUCLEOTIDE SEQUENCE.
[2]	"Alpha-conotoxin EI, a new nicotinic acetylcholine receptor antagonist with novel selectivity." Martinez J.S., Olivera B.M., Gray W.R., Craig A.G., Groebe D.R., Abramson S.N., McIntosh J.M. Biochemistry 34:14519-14526(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 44-61, FUNCTION, SYNTHESIS, DISULFIDE BONDS, HYDROXYLATION AT PRO-46, AMIDATION AT CYS-61, MASS SPECTROMETRY. Tissue: Venom.
[3]	"Novel alpha-conotoxins from Conus spurius and the alpha-conotoxin EI share high-affinity potentiation and low-affinity inhibition of nicotinic acetylcholine receptors." Lopez-Vera E., Aguilar M.B., Schiavon E., Marinzi C., Ortiz E., Restano Cassulini R., Batista C.V.F., Possani L.D., Heimer de la Cotera E.P., Peri F., Becerril B., Wanke E. FEBS J. 274:3972-3985(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[4]	"Solution conformation of alpha-conotoxin EI, a neuromuscular toxin specific for the alpha 1/delta subunit interface of torpedo nicotinic acetylcholine receptor." Park K.-H., Suk J.-E., Jacobsen R., Gray W.R., McIntosh J.M., Han K.-H. J. Biol. Chem. 276:49028-49033(2001) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 44-61, HYDROXYLATION AT PRO-46, AMIDATION AT CYS-61, DISULFIDE BONDS.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BD394990 Unassigned DNA. No translation available.

PIR

A58589.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1K64	NMR	-	A	44-61	[»]

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ConoServer

50. EI.

Family and domain databases

InterPro

IPR009958. Conotoxin_a-typ.
IPR018072. Conotoxin_a-typ_CS.
[Graphical view]

Pfam

PF07365. Toxin_8. 1 hit.
[Graphical view]

PROSITE

PS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P50982.

Entry information

Entry name

CA1_CONER

Accession

Primary (citable) accession number: P50982

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	March 23, 2010
Last modified:	May 1, 2013
This is version 57 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program