P17684 (CKT_CONTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Conantokin-T Short name=Con-T
Organism	Conus tulipa (Fish-hunting cone snail) (Tulip cone)
Taxonomic identifier	6495 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Hypsogastropoda › Neogastropoda › Conoidea › Conidae › Conus

Protein attributes

Sequence length	21 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Conantokins inhibit N-methyl-D-aspartate (NMDA) receptors. This toxin inhibits both NR2A and NR2B subunits of N-methyl-D-aspartate (NMDA) receptor-mediated calcium influx in central nervous system neurons. Induces sleep-like symptoms in young mice and hyperactivity in older mice. Ref.2
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom duct.
Pharmaceutical use	Failed in phase II clinical trial. Was tested by Cognetix Inc. to treat antinociceptive effects in several models of injury-induced pain.
Miscellaneous	The mature peptide does not contain cysteine residue.
Sequence similarities	Belongs to the conotoxin B superfamily.

Ontologies

Keywords
Cellular component	Secreted
Ligand	Calcium
Molecular function	Ion channel impairing toxin Ionotropic glutamate receptor inhibitor Neurotoxin Postsynaptic neurotoxin Toxin
PTM	Amidation Gamma-carboxyglutamic acid
Technical term	3D-structure Direct protein sequencing Pharmaceutical
Gene Ontology (GO)
Cellular_component	other organism postsynaptic membrane 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 – 21

21

Conantokin-T

PRO_0000044504

Sites

Site

5

1

Important for selectivity

Amino acid modifications

Modified residue

3

1

4-carboxyglutamate Ref.1

Modified residue

4

1

4-carboxyglutamate Ref.1

Modified residue

10

1

4-carboxyglutamate Ref.1

Modified residue

14

1

4-carboxyglutamate Ref.1

Modified residue

21

1

Alanine amide Ref.1

Experimental info

Mutagenesis

5

1

Y → F: No loss of inhibition of NR1a/NR2B receptor; little loss of inhibition of NR1a/NR2A receptor. Ref.3

Mutagenesis

5

1

Y → V: Little loss of inhibition of NR1a/NR2B receptor; important loss of inhibition of NR1a/NR2A receptor. Ref.3

Mutagenesis

5

1

Y → W: Little loss of inhibition of NR1a/NR2B receptor; complete loss of inhibition of NR1a/NR2A receptor. Ref.3

Secondary structure

1

.

.

.

.

.

21

Helix Strand Turn

Details...

Helix

2 – 15

14

Helix

17 – 20

4

Sequences

	Sequence		Length	Mass (Da)
	P17684 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: 7F7B893AC4842C38	FASTA	21	2,509
	10 20 GEEEYQKMLE NLREAEVKKN A

References

[1]	"Conantokin-T. A gamma-carboxyglutamate containing peptide with N-methyl-D-aspartate antagonist activity." Haack J.A., Rivier J.E., Parks T.N., Mena E.E., Cruz L.J., Olivera B.M. J. Biol. Chem. 265:6025-6029(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE. Tissue: Venom.
[2]	"Diversity of Conus neuropeptides." Olivera B.M., Rivier J., Clark C., Ramilo C.A., Corpuz G.P., Abogadie F.C., Mena E.E., Woodward S.R., Hillyard D.R., Cruz L.J. Science 249:257-263(1990) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[3]	"The amino acid residue at sequence position 5 in the conantokin peptides partially governs subunit-selective antagonism of recombinant N-methyl-D-aspartate receptors." Klein R.C., Prorok M., Galdzicki Z., Castellino F.J. J. Biol. Chem. 276:26860-26867(2001) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TYR-5, SITE.
[4]	"Powerful antinociceptive effects of the cone snail venom-derived subtype-selective NMDA receptor antagonists conantokins G and T." Malmberg A.B., Gilbert H., McCabe R.T., Basbaum A.I. Pain 101:109-116(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHARMACEUTICAL.
[5]	"The NMR solution structure of the NMDA receptor antagonist, conantokin-T, in the absence of divalent metal ions." Warder S.E., Chen Z., Zhu Y., Prorok M., Castellino F.J., Ni F. FEBS Lett. 411:19-26(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[6]	"Determination of the solution structures of conantokin-G and conantokin-T by CD and NMR spectroscopy." Skjaerbaek N., Nielsen K.J., Lewis R.J., Alewood P.F., Craik D.J. J. Biol. Chem. 272:2291-2299(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.

Cross-references

Sequence databases

PIR

A35225.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ONT	NMR	-	A	1-21	[»]

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ConoServer

1269. Conantokin-T.

Family and domain databases

InterPro

IPR005918. Conantokin_CS.
[Graphical view]

Pfam

PF10550. Toxin_36. 1 hit.
[Graphical view]

PROSITE

PS60025. CONANTOKIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P17684.

Entry information

Entry name

CKT_CONTU

Accession

Primary (citable) accession number: P17684

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	May 1, 2013
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program