P01522 (CO16A_CONGE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Omega-conotoxin GVIA Alternative name(s): SNX-124 Shaker peptide Cleaved into the following 2 chains: Omega-conotoxin GVIB Omega-conotoxin GVIC
Organism	Conus geographus (Geography cone) (Nubecula geographus)
Taxonomic identifier	6491 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Mollusca › Gastropoda › Caenogastropoda › Hypsogastropoda › Neogastropoda › Conoidea › Conidae › Conus

Protein attributes

Sequence length	73 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	Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav).
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom duct.
Domain	The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. The cysteine framework is VI/VII (C-C-CC-C-C).
Sequence similarities	Belongs to the conotoxin O1 superfamily.

Ontologies

Keywords
Cellular component	Secreted
Domain	Knottin Signal
Molecular function	Calcium channel inhibitor Ionic channel inhibitor Neurotoxin Presynaptic neurotoxin Toxin
PTM	Amidation Disulfide bond Hydroxylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	pathogenesis Inferred from electronic annotation. Source: InterPro
Cellular component	other organism presynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	calcium channel 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

Signal peptide

1 – 22

22

Potential

Propeptide

23 – 45

23

PRO_0000034906

Peptide

46 – 73

28

Omega-conotoxin GVIB Ref.3

PRO_0000034907

Peptide

46 – 72

27

Omega-conotoxin GVIA Ref.2

PRO_0000034908

Peptide

46 – 71

26

Omega-conotoxin GVIC

PRO_0000034909

Amino acid modifications

Modified residue

49

1

4-hydroxyproline Ref.2

Modified residue

55

1

4-hydroxyproline Ref.2

Modified residue

66

1

4-hydroxyproline Ref.2

Modified residue

72

1

Tyrosine amide; in form omega-conotoxin GVIA

Disulfide bond

46 ↔ 61

Ref.4 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Disulfide bond

53 ↔ 64

Ref.4 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Disulfide bond

60 ↔ 71

Ref.4 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Experimental info

Mutagenesis

47

1

K → A: Strong decrease in activity. Ref.5 Ref.7

Mutagenesis

58

1

Y → A: Strong decrease in activity. Ref.6 Ref.7

Mutagenesis

58

1

Y → F: Decrease in affinity. Ref.6 Ref.7

Mutagenesis

62

1

R → A: Decrease in potency, but not in affinity. Ref.5 Ref.7

Mutagenesis

67

1

Y → A: Decrease in potency, but not in affinity. Ref.7

Mutagenesis

69

1

K → A: Decrease in potency, but not in affinity. Ref.5 Ref.7

Mutagenesis

70

1

R → A: No change in activity. Ref.5

Secondary structure

1

.

.

.

.

.

73

Helix Strand Turn

Details...

Beta strand

60 – 62

3

Turn

66 – 69

4

Sequences

	Sequence		Length	Mass (Da)
	P01522 [UniParc]. Last modified February 1, 1994. Version 2. Checksum: 51A8C8FA630F7175	FASTA	73	7,851
	10 20 30 40 50 60 MKLTCVVIVA VLLLTACQLI TADDSRGTQK HRALGSTTEL SLSTRCKSPG SSCSPTSYNC 70 CRSCNPYTKR CYG

References

[1]	"Precursor structure of omega-conotoxin GVIA determined from a cDNA clone." Colledge C.J., Hunsperger J.P., Imperial J.S., Hillyard D.R. Toxicon 30:1111-1116(1992) [PubMed: 1440648] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Purification and sequence of a presynaptic peptide toxin from Conus geographus venom." Olivera B.M., McIntosh J.M., Cruz L.J., Luque F.A., Gray W.R. Biochemistry 23:5087-5090(1984) [PubMed: 6509012] [Abstract] Cited for: PROTEIN SEQUENCE OF 46-72 (GVIA).
[3]	"Peptide neurotoxins from fish-hunting cone snails." Olivera B.M., Gray W.R., Zeikus R.D., McIntosh J.M., Varga J., Rivier J.E., de Santos V., Cruz L.J. Science 230:1338-1343(1985) [PubMed: 4071055] [Abstract] Cited for: PROTEIN SEQUENCE OF 46-73 (GVIB AND GVIC).
[4]	"Synthesis and secondary-structure determination of omega-conotoxin GVIA: a 27-peptide with three intramolecular disulfide bonds." Nishiuchi Y., Kumagaye K., Noda Y., Watanabe T.X., Sakakibara S. Biopolymers 25:S61-S68(1986) [PubMed: 3779030] [Abstract] Cited for: SYNTHESIS OF 46-72 (GVIA), DISULFIDE BONDS.
[5]	"Role of basic residues for the binding of omega-conotoxin GVIA to N-type calcium channels." Sato K., Park N.G., Kohno T., Maeda T., Kim J.-I., Kato R., Takahashi M. Biochem. Biophys. Res. Commun. 194:1292-1296(1993) [PubMed: 8394704] [Abstract] Cited for: MUTAGENESIS OF LYS-47; ARG-62; LYS-69 AND ARG-70.
[6]	"Hydroxyl group of Tyr13 is essential for the activity of omega-conotoxin GVIA, a peptide toxin for N-type calcium channel." Kim J.-I., Takahashi M., Ogura A., Kohno T., Kudo Y., Sato K. J. Biol. Chem. 269:23876-23878(1994) [PubMed: 7929033] [Abstract] Cited for: MUTAGENESIS OF TYR-58.
[7]	"Structure-function relationships of omega-conotoxin GVIA. Synthesis, structure, calcium channel binding, and functional assay of alanine-substituted analogues." Lew M.J., Flinn J.P., Pallaghy P.K., Murphy R., Whorlow S.L., Wright C.E., Norton R.S., Angus J.A. J. Biol. Chem. 272:12014-12023(1997) [PubMed: 9115267] [Abstract] Cited for: SYNTHESIS OF 46-72 (GVIA), MUTAGENESIS OF LYS-47; TYR-58; ARG-62; TYR-67 AND LYS-69, STRUCTURE BY NMR OF 46-72 (GVIA).
[8]	"Three-dimensional structure of omega-conotoxin GVIA determined by 1H NMR." Sevilla P., Bruix M., Santoro J., Gago F., Garcia A.G., Rico M. Biochem. Biophys. Res. Commun. 192:1238-1244(1993) [PubMed: 8343203] [Abstract] Cited for: STRUCTURE BY NMR OF 46-72 (GVIA), DISULFIDE BONDS.
[9]	"Solution structure of omega-conotoxin GVIA using 2-D NMR spectroscopy and relaxation matrix analysis." Davis J.H., Bradley E.K., Miljanich G.P., Nadasdi L., Ramachandran J., Basus V.J. Biochemistry 32:7396-7405(1993) [PubMed: 8338837] [Abstract] Cited for: STRUCTURE BY NMR OF 46-72 (GVIA), DISULFIDE BONDS.
[10]	"Three-dimensional structure in solution of the calcium channel blocker omega-conotoxin." Pallaghy P.K., Duggan B.M., Pennington M.W., Norton R.S. J. Mol. Biol. 234:405-420(1993) [PubMed: 8230223] [Abstract] Cited for: STRUCTURE BY NMR OF 46-72 (GVIA), DISULFIDE BONDS.
[11]	"Solution structure of the calcium channel antagonist omega-conotoxin GVIA." Skalicky J.J., Metzler W.J., Ciesla D.J., Galdes A., Pardi A. Protein Sci. 2:1591-1603(1993) [PubMed: 8251934] [Abstract] Cited for: STRUCTURE BY NMR OF 46-72 (GVIA), DISULFIDE BONDS.
[12]	"Refined solution structure of omega-conotoxin GVIA: implications for calcium channel binding." Pallaghy P.K., Norton R.S. J. Pept. Res. 53:343-351(1999) [PubMed: 10231724] [Abstract] Cited for: STRUCTURE BY NMR OF 46-72 (GVIA), DISULFIDE BONDS.
[13]	"Structure-activity relationships of omega-conotoxins at N-type voltage-sensitive calcium channels." Nielsen K.J., Schroeder T., Lewis R.J. J. Mol. Recognit. 13:55-70(2000) [PubMed: 10822250] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M84612 mRNA. Translation: AAA81590.1.

PIR

NTKN6G. A44006.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OMC	NMR	-	A	46-72	[»]
1TR6	NMR	-	A	46-72	[»]
1TTL	NMR	-	A	46-72	[»]
2CCO	NMR	-	A	46-72	[»]

ProteinModelPortal

P01522.

SMR

P01522. Positions 46-72.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ConoServer

820. GVIA precursor.

Family and domain databases

InterPro

IPR004214. Conotoxin.
IPR012321. Conotoxin_omega-typ_CS.
[Graphical view]

Pfam

PF02950. Conotoxin. 1 hit.
[Graphical view]

PROSITE

PS60004. OMEGA_CONOTOXIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

CO16A_CONGE

Accession

Primary (citable) accession number: P01522

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	February 1, 1994
Last modified:	November 16, 2011
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program