Q26443 (CO16B_CONMR) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Mu-conotoxin MrVIB Alternative name(s): CGX-1002
Organism	Conus marmoreus (Marble cone)
Taxonomic identifier	42752 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Mollusca › Gastropoda › Caenogastropoda › Hypsogastropoda › Neogastropoda › Conoidea › Conidae › Conus

Protein attributes

Sequence length	82 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	Mu-conotoxins block voltage-gated sodium channels. Has a preference for Nav1.4/SCN4A over Nav1.2/SCN2A sodium channels. Blocks Nav channels by interacting mainly with the C-terminal part of the pore loop of domain-3. Also blocks fast-inactivating calcium current. Blocks Nav1.8/SCN10A sodium channels and has potent and long-lasting local anesthetic effects. Can also block propagation of action potentials in A- and C-fibers in sciatic nerve as well as skeletal muscle in isolated preparations. Ref.4 Ref.5
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).
Pharmaceutical use	Is under preclinical trial by Cognetix Inc under the name CGX-1002 as a local anesthetic agent.
Sequence similarities	Belongs to the conotoxin O1 superfamily.
Mass spectrometry	Molecular mass is 3404.8 Da from positions 52 - 82. Determined by LSI. Ref.1 Molecular mass is 3404.9 Da from positions 52 - 82. Determined by ESI. Ref.2

Ontologies

Keywords
Cellular component	Secreted
Domain	Knottin Signal
Molecular function	Ionic channel inhibitor Neurotoxin Sodium channel inhibitor Toxin
PTM	Cleavage on pair of basic residues Disulfide bond
Technical term	3D-structure Direct protein sequencing Pharmaceutical
Gene Ontology (GO)
Biological process	pathogenesis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	sodium 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 – 49

27

PRO_0000034902

Peptide

52 – 82

31

Mu-conotoxin MrVIB Ref.1 Ref.2

PRO_0000034903

Amino acid modifications

Disulfide bond

53 ↔ 71

Ref.3

Disulfide bond

60 ↔ 76

Ref.3

Disulfide bond

70 ↔ 81

Ref.3

Secondary structure

1

.

.

.

82

Helix Strand Turn

Details...

Beta strand

69 – 71

3

Sequences

	Sequence		Length	Mass (Da)
	Q26443 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: B617F8652A48F5D6	FASTA	82	9,210
	10 20 30 40 50 60 MKLTCMMIVA VLFLTAWTLV MADDSNNGLA NHFLKSRDEM EDPEASKLEK RACSKKWEYC 70 80 IVPILGFVYC CPGLICGPFV CV

References

[1]	"A new family of conotoxins that blocks voltage-gated sodium channels." McIntosh J.M., Hasson A., Spira M.E., Gray W.R., Li W., Marsh M., Hillyard D.R., Olivera B.M. J. Biol. Chem. 270:16796-16802(1995) [PubMed: 7622492] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 52-82, MASS SPECTROMETRY. Tissue: Venom.
[2]	"New sodium channel-blocking conotoxins also affect calcium currents in Lymnaea neurons." Fainzilber M., van der Schors R., Lodder J.C., Li K.W., Geraerts W.P., Kits K.S. Biochemistry 34:5364-5371(1995) [PubMed: 7727394] [Abstract] Cited for: PROTEIN SEQUENCE OF 52-82, CHARACTERIZATION, MASS SPECTROMETRY. Tissue: Venom.
[3]	"Structures of muO-conotoxins from Conus marmoreus. Inhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian sensory neurons." Daly N.L., Ekberg J.A., Thomas L., Adams D.J., Lewis R.J., Craik D.J. J. Biol. Chem. 279:25774-25782(2004) [PubMed: 15044438] [Abstract] Cited for: STRUCTURE BY NMR OF 52-82, DISULFIDE BONDS.
[4]	"Synthetic muO-conotoxin MrVIB blocks TTX-resistant sodium channel NaV1.8 and has a long-lasting analgesic activity." Bulaj G., Zhang M.M., Green B.R., Fiedler B., Layer R.T., Wei S., Nielsen J.S., Low S.J., Klein B.D., Wagstaff J.D., Chicoine L., Harty T.P., Terlau H., Yoshikami D., Olivera B.M. Biochemistry 45:7404-7414(2006) [PubMed: 16752929] [Abstract] Cited for: SYNTHESIS OF 52-82, FUNCTION.
[5]	"The muO-conotoxin MrVIA inhibits voltage-gated sodium channels by associating with domain-3." Zorn S., Leipold E., Hansel A., Bulaj G., Olivera B.M., Terlau H., Heinemann S.H. FEBS Lett. 580:1360-1364(2006) [PubMed: 16458302] [Abstract] Cited for: SYNTHESIS OF 52-82, FUNCTION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S78990 mRNA. Translation: AAB34916.1.

PIR

B58586.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RMK	NMR	-	A	52-82	[»]

ProteinModelPortal

Q26443.

SMR

Q26443. Positions 52-82.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ConoServer

597. MrVIB precursor.

Family and domain databases

InterPro

IPR004214. Conotoxin.
[Graphical view]

Pfam

PF02950. Conotoxin. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

CO16B_CONMR

Accession

Primary (citable) accession number: Q26443

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1996
Last modified:	November 16, 2011
This is version 73 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program