P01519 (CA1A_CONGE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Alpha-conotoxin GIA Cleaved into the following chain: Alpha-conotoxin GI Alternative name(s): G1
Organism	Conus geographus (Geography cone) (Nubecula geographus)
Taxonomic identifier	6491 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Hypsogastropoda › Neogastropoda › Conoidea › Conidae › Conus

Protein attributes

Sequence length	15 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. The higher affinity site for alpha-conotoxin GI is the alpha/delta site on mouse muscle-derived BC3H-1 receptor, and the other site (alpha/gamma site) on nicotinic receptors from Torpedo californica electric organ.
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 GI, 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 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

Peptide

1 – 15

15

Alpha-conotoxin GIA

PRO_0000034873

Peptide

1 – 13

13

Alpha-conotoxin GI

PRO_0000034874

Amino acid modifications

Modified residue

13

1

Cysteine amide; in alpha-conotoxin GI

Modified residue

15

1

Lysine amide; in form alpha-conotoxin GIA

Disulfide bond

2 ↔ 7

Ref.2 Ref.3 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Disulfide bond

3 ↔ 13

Ref.2 Ref.3 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Experimental info

Mutagenesis

9

1

R → A: Reduction in affinity for both alpha/delta and alpha/gamma sites on BC3H-1 receptors and loss of affinity for both alpha/delta and alpha/gamma sites on Torpedo receptors (in GI). Ref.6

Secondary structure

1

.

.

.

15

Helix Strand Turn

Details...

Helix

5 – 10

6

Sequences

	Sequence		Length	Mass (Da)
	P01519 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 2AE73EE90F8C2E19	FASTA	15	1,628
	10 ECCNPACGRH YSCGK

References

[1]	"Peptide toxins from Conus geographus venom." Gray W.R., Luque A., Olivera B.M., Barrett J., Cruz L.J. J. Biol. Chem. 256:4734-4740(1981) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE.
[2]	"Primary and secondary structure of conotoxin GI, a neurotoxic tridecapeptide from a marine snail." Nishiuchi Y., Sakakibara S. FEBS Lett. 148:260-262(1982) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS IN GI, SYNTHESIS OF GI.
[3]	"Conotoxin GI: disulfide bridges, synthesis, and preparation of iodinated derivatives." Gray W.R., Luque F.A., Galyean R., Atherton E., Sheppard R.C., Stone B.L., Reyes A., Alford J., McIntosh M., Olivera B.M., Cruz L.J., Rivier J. Biochemistry 23:2796-2802(1984) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS IN GI, SYNTHESIS OF GI.
[4]	"The alpha-conotoxins GI and MI distinguish between the nicotinic acetylcholine receptor agonist sites while SI does not." Hann R.M., Pagan O.R., Eterovic V.A. Biochemistry 33:14058-14063(1994) [PubMed] [Europe PMC] [Abstract] Cited for: COMPARISON WITH ALPHA-CONOTOXIN SI AND ALPHA-CONOTOXIN MI.
[5]	"Alpha-conotoxins selectively inhibit one of the two acetylcholine binding sites of nicotinic receptors." Groebe D.R., Dumm J.M., Levitan E.S., Abramson S.N. Mol. Pharmacol. 48:105-111(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PHARMACOLOGICAL CHARACTERIZATION ON MOUSE MUSCLE-DERIVED BC3H-1 CELLS AND TORPEDO ELECTRIC ORGAN.
[6]	"Determinants involved in the affinity of alpha-conotoxins GI and SI for the muscle subtype of nicotinic acetylcholine receptors." Groebe D.R., Gray W.R., Abramson S.N. Biochemistry 36:6469-6474(1997) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ARG-9.
[7]	"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, ROLE OF HYDROXYLATION.
[8]	"Three-dimensional structure of the alpha-conotoxin GI at 1.2-A resolution." Guddat L.W., Martin J.A., Shan L., Edmundson A.B., Gray W.R. Biochemistry 35:11329-11335(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF GI, DISULFIDE BONDS.
[9]	"Solution conformation of conotoxin GI determined by 1H nuclear magnetic resonance spectroscopy and distance geometry calculations." Kobayashi Y., Ohkubo T., Kyogoku Y., Nishiuchi Y., Sakakibara S., Braun W., Go N. Biochemistry 28:4853-4860(1989) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF GI, DISULFIDE BONDS.
[10]	"Solution structures of alpha-conotoxin G1 determined by two-dimensional NMR spectroscopy." Pardi A., Galdes A., Florance J., Maniconte D. Biochemistry 28:5494-5501(1989) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF GI, DISULFIDE BONDS.
[11]	"Two distinct structures of alpha-conotoxin GI in aqueous solution." Maslennikov I.V., Sobol A.G., Gladky K.V., Lugovskoy A.A., Ostrovsky A.G., Tsetlin V.I., Ivanov V.T., Arseniev A.S. Eur. J. Biochem. 254:238-247(1998) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF GI, DISULFIDE BONDS.
[12]	"Structure determination of the three disulfide bond isomers of alpha-conotoxin GI: a model for the role of disulfide bonds in structural stability." Gehrmann J., Alewood P.F., Craik D.J. J. Mol. Biol. 278:401-415(1998) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF GI, DISULFIDE BONDS.
[13]	"NMR solution conformation of an antitoxic analogue of alpha-conotoxin GI: identification of a common nicotinic acetylcholine receptor alpha(1)-subunit binding surface for small ligands and alpha-conotoxins." Mok K.H., Han K.H. Biochemistry 38:11895-11904(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF AN ANTITOXIC ANALOG OF GI, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

PIR

NTKNAG. A01782.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NOT	X-ray	1.20	A	1-13	[»]
1QS3	NMR	-	A	4-12	[»]
1XGA	NMR	-	A	1-13	[»]
1XGB	NMR	-	A	1-13	[»]
1XGC	NMR	-	A	1-13	[»]
2FR9	NMR	-	A	1-11	[»]
2FRB	NMR	-	A	1-13	[»]

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ConoServer

74. GI.
22. GIA.

Family and domain databases

InterPro

IPR018072. Conotoxin_a-typ_CS.
[Graphical view]

PROSITE

PS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P01519.

Entry information

Entry name

CA1A_CONGE

Accession

Primary (citable) accession number: P01519

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 1, 2013
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program