P37300 (CO7C_CONMA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Omega-conotoxin MVIIC Alternative name(s): SNX-230
Organism	Conus magus (Magus cone) (Magician's cone snail)
Taxonomic identifier	6492 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Hypsogastropoda › Neogastropoda › Conoidea › Conidae › Conus

Protein attributes

Sequence length	29 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	Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels (Cav). This toxin preferentially blocks P/Q-type calcium channels (Cav2.1/CACNA1A). Ref.1
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).
Post-translational modification	Not hydroxylated; hydroxylation, on a synthetic hydroxylated MVIIC, has a significant impact on the oxidative folding but not on the biological activity.
Sequence similarities	Belongs to the conotoxin O1 superfamily.

Ontologies

Keywords
Cellular component	Secreted
Domain	Knottin
Molecular function	Calcium channel inhibitor Ion channel impairing toxin Neurotoxin Presynaptic neurotoxin Toxin
PTM	Amidation Disulfide bond
Technical term	3D-structure
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

Propeptide

‹1 – 2

›2

PRO_0000034916

Peptide

3 – 28

26

Omega-conotoxin MVIIC

PRO_0000034917

Sites

Site

15

1

Important for calcium channel binding

Amino acid modifications

Modified residue

28

1

Cysteine amide

Disulfide bond

3 ↔ 18

Ref.4 Ref.5

Disulfide bond

10 ↔ 22

Ref.4 Ref.5

Disulfide bond

17 ↔ 28

Ref.4 Ref.5

Experimental info

Mutagenesis

15

1

Y → A: High decrease in binding. Ref.2

Non-terminal residue

1

1

Secondary structure

1

.

.

.

.

.

29

Helix Strand Turn

Details...

Turn

12 – 15

4

Beta strand

17 – 20

4

Sequences

	Sequence		Length	Mass (Da)
	P37300 [UniParc]. Last modified October 1, 1994. Version 1. Checksum: AC7A68948474728A	FASTA	29	3,071
	10 20 TRCKGKGAPC RKTMYDCCSG SCGRRGKCG

References

[1]	"A new Conus peptide ligand for mammalian presynaptic Ca2+ channels." Hillyard D.R., Monje V.D., Mintz I.M., Bean B.P., Nadasdi L., Ramachandran J., Miljanich G.P., Azimi-Zoonooz A., McIntosh J.M., Cruz L.J., Imperial J.S., Olivera B.M. Neuron 9:69-77(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 3-28, FUNCTION.
[2]	"Tyr13 is essential for the binding of omega-conotoxin MVIIC to the P/Q-type calcium channel." Kim J.-I., Takahashi M., Martin-Moutot N., Seagar M.J., Ohtake A., Sato K. Biochem. Biophys. Res. Commun. 214:305-309(1995) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TYR-15.
[3]	"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 3-28, ROLE OF HYDROXYLATION.
[4]	"Solution structure of omega-conotoxin MVIIC, a high affinity ligand of P-type calcium channels, using 1H NMR spectroscopy and complete relaxation matrix analysis." Farr-Jones S., Miljanich G.P., Nadasdi L., Ramachandran J., Basus V.J. J. Mol. Biol. 248:106-124(1995) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 3-28, DISULFIDE BONDS.
[5]	"Structure-activity relationships of omega-conotoxins MVIIA, MVIIC and 14 loop splice hybrids at N and P/Q-type calcium channels." Nielsen K.J., Adams D., Thomas L., Bond T., Alewood P.F., Craik D.J., Lewis R.J. J. Mol. Biol. 289:1405-1421(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 3-28, DISULFIDE BONDS.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S40826 mRNA. Translation: AAB22674.1.

PIR

JH0699.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CNN	NMR	-	A	3-28	[»]
1OMN	NMR	-	A	3-28	[»]
1V4Q	NMR	-	A	3-26	[»]

ProteinModelPortal

P37300.

SMR

P37300. Positions 3-28.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ConoServer

822. MVIIC precursor.

Family and domain databases

InterPro

IPR012321. Conotoxin_omega-typ_CS.
[Graphical view]

PROSITE

PS60004. OMEGA_CONOTOXIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P37300.

Entry information

Entry name

CO7C_CONMA

Accession

Primary (citable) accession number: P37300

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 1, 1994
Last modified:	April 3, 2013
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program