P18511 (CO16A_CONTE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Delta-conotoxin TxVIA Short name=TxIA Alternative name(s): Conotoxin King-Kong 0 Short name=KK-0
Organism	Conus textile (Cloth-of-gold cone)
Taxonomic identifier	6494 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Hypsogastropoda › Neogastropoda › Conoidea › Conidae › Conus

Protein attributes

Sequence length	78 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	Delta-conotoxins bind to site 6 of voltage-gated sodium channels (Nav) and inhibit the inactivation process. Binding of this toxin is strongly calcium-dependent but not voltage-dependent. The binding site is most likely on the extracellular side of the sodium channel. Binds receptor sites on both mollusk and rat central nervous system, but despite its high affinity binding to rat sodium channel, it has no functional effect in vivo and in vitro on it. Has also no effect on Gambusia fish. Is important in mollusk for the paralysis of the prey. Upon injection of the peptide, a subordinate lobster assumes an exaggerated dominant posture (of a 'King-Kong' lobster!).
Subcellular location	Secreted Ref.4.
Tissue specificity	Expressed by the venom duct. Ref.4
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).
Miscellaneous	Veratridine increases the rate of dissociation in a dose-dependent manner.
Sequence similarities	Belongs to the conotoxin O1 superfamily.
Mass spectrometry	Molecular mass is 3034.2±0.05 Da from positions 52 - 78. Determined by ESI. Without oxidation at Met-59. Ref.4 Molecular mass is 3050.189±0.05 Da from positions 52 - 78. Determined by ESI. With oxidation at Met-59. Ref.4

Ontologies

Keywords
Cellular component	Secreted
Domain	Knottin Signal
Molecular function	Ion channel impairing toxin Neurotoxin Sodium channel inhibitor Toxin
PTM	Cleavage on pair of basic residues Disulfide bond
Technical term	3D-structure Direct protein sequencing
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_0000034900

Peptide

52 – 78

27

Delta-conotoxin TxVIA Ref.2 Ref.3 Ref.4

PRO_0000034901

Sites

Site

59

1

Susceptible to oxidation

Amino acid modifications

Disulfide bond

53 ↔ 68

Ref.4 Ref.7 Ref.8

Disulfide bond

60 ↔ 72

Ref.4 Ref.7 Ref.8

Disulfide bond

67 ↔ 77

Ref.4 Ref.7 Ref.8

Secondary structure

1

.

.

.

.

.

78

Helix Strand Turn

Details...

Beta strand

62 – 64

3

Beta strand

67 – 70

4

Sequences

	Sequence		Length	Mass (Da)
	P18511 [UniParc]. Last modified November 1, 1990. Version 1. Checksum: C5CBFD462AD40A35	FASTA	78	8,760
	10 20 30 40 50 60 MKLTCMMIVA VLFLTAWTFA TADDPRNGLG NLFSNAHHEM KNPEASKLNK RWCKQSGEMC 70 NLLDQNCCDG YCIVLVCT

References

[1]	"Constant and hypervariable regions in conotoxin propeptides." Woodward S.R., Cruz L.J., Olivera B.M., Hillyard D.R. EMBO J. 9:1015-1020(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"A molluscivorous Conus toxin: conserved frameworks in conotoxins." Hillyard D.R., Olivera B.M., Woodward S.R., Corpuz G.P., Gray W.R., Ramilo C.A., Cruz L.J. Biochemistry 28:358-361(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 52-78.
[3]	"Mollusc-specific toxins from the venom of Conus textile neovicarius." Fainzilber M., Gordon D., Hasson A., Spira M.E., Zlotkin E. Eur. J. Biochem. 202:589-595(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 52-78. Strain: Neovicarius.
[4]	"Rapid sensitive analysis of cysteine rich peptide venom components." Ueberheide B.M., Fenyo D., Alewood P.F., Chait B.T. Proc. Natl. Acad. Sci. U.S.A. 106:6910-6915(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 52-78, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MASS SPECTROMETRY, DISULFIDE BONDS, OXIDATION AT MET-59. Tissue: Venom.
[5]	"Alteration of sodium currents by new peptide toxins from the venom of a molluscivorous Conus snail." Hasson A., Fainzilber M., Gordon D., Zlotkin E., Spira M.E. Eur. J. Neurosci. 5:56-64(1993) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[6]	"A new neurotoxin receptor site on sodium channels is identified by a conotoxin that affects sodium channel inactivation in molluscs and acts as an antagonist in rat brain." Fainzilber M., Kofman O., Zlotkin E., Gordon D. J. Biol. Chem. 269:2574-2580(1994) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[7]	"Delta-conotoxin GmVIA, a novel peptide from the venom of Conus gloriamaris." Shon K.-J., Hasson A., Spira M.E., Cruz L.J., Gray W.R., Olivera B.M. Biochemistry 33:11420-11425(1994) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS. Tissue: Venom.
[8]	"Three-dimensional solution structure of the sodium channel agonist/antagonist delta-conotoxin TxVIA." Kohno T., Sasaki T., Kobayashi K., Fainzilber M., Sato K. J. Biol. Chem. 277:36387-36391(2002) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X53283 mRNA. Translation: CAA37377.1.

PIR

S12513.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FU3	NMR	-	A	52-78	[»]

ProteinModelPortal

P18511.

SMR

P18511. Positions 52-78.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ConoServer

598. TxVIA precursor.

Family and domain databases

InterPro

IPR004214. Conotoxin.
IPR012322. Conotoxin_d-typ_CS.
[Graphical view]

Pfam

PF02950. Conotoxin. 1 hit.
[Graphical view]

PROSITE

PS60005. DELTA_CONOTOXIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P18511.

Entry information

Entry name

CO16A_CONTE

Accession

Primary (citable) accession number: P18511

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	May 1, 2013
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program