P82228 (TJT1C_HADVE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Kappa-hexatoxin-Hv1c Short name=Kappa-HXTX-Hv1c Alternative name(s): Janus-atracotoxin-Hv1c Short name=Janus-AcTx-Hv1c Kappa-atracotoxin-Hv1c Short name=Kappa-AcTx-Hv1c
Organism	Hadronyche versuta (Blue mountains funnel-web spider) (Atrax versutus)
Taxonomic identifier	6904 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Chelicerata › Arachnida › Araneae › Mygalomorphae › Hexathelidae › Hadronyche

Protein attributes

Sequence length	37 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This excitatory toxin inhibits insect calcium-activated potassium channels (Slo-type). Pan-neuronal expression in Drosophila is lethal but flies engineered to express the toxin only in clock neurons have defects in circadian rhythm but a normal lifespan. Ref.1 Ref.4 Ref.5 Ref.6
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Domain	The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.
Toxic dose	LD50 of recombinant toxin is 320 +-20 pmol/g (according to Ref.2) or 91 +-5 pmol/g (according to Ref.3) when injected into house flies (Musca domestica). Ref.2 Ref.3
Sequence similarities	Belongs to the janus-atracotoxin family.

Ontologies

Keywords
Cellular component	Secreted
Domain	Knottin
Molecular function	Ion channel impairing toxin Neurotoxin Potassium channel inhibitor Toxin
PTM	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	potassium 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

Peptide

1 – 37

37

Kappa-hexatoxin-Hv1c

PRO_0000044998

Sites

Site

2

1

Important for the neurotoxic activity

Site

8

1

Critical for the neurotoxic activity

Site

9

1

Critical for the neurotoxic activity

Site

13

1

Critical for the neurotoxic activity

Site

14

1

Critical for the neurotoxic activity

Site

29

1

Important for the neurotoxic activity

Site

31

1

Critical for the neurotoxic activity

Amino acid modifications

Disulfide bond

3 ↔ 17

Disulfide bond

10 ↔ 22

Disulfide bond

13 ↔ 14

Disulfide bond

16 ↔ 32

Experimental info

Mutagenesis

1 – 2

2

Missing: 73-fold decrease in toxicity to flies. Ref.2 Ref.3

Mutagenesis

1

1

Missing: No change in toxicity. Ref.3

Mutagenesis

2

1

I → A: 7-fold decrease in toxicity to flies. Ref.2

Mutagenesis

8

1

R → A: 98-fold decrease in toxicity to flies. Ref.2

Mutagenesis

8

1

R → E: 270-fold decrease in toxicity to flies. Ref.2

Mutagenesis

9

1

P → A: 269-fold decrease in toxicity to flies. Ref.2

Mutagenesis

13 – 14

2

CC → SS: 423-fold decrease in toxicity to flies.

Mutagenesis

29

1

V → A: 13-fold decrease in toxicity to flies. Ref.2

Mutagenesis

31

1

Y → A: 162-fold decrease in toxicity to flies. Ref.2

Mutagenesis

31

1

Y → F: 1.8-fold decrease in toxicity to flies. Ref.2

Mutagenesis

35 – 37

3

Missing: No change in toxicity to flies.

Mutagenesis

36 – 37

2

Missing: No change in toxicity.

Secondary structure

1

.

.

.

.

.

37

Helix Strand Turn

Details...

Beta strand

20 – 24

5

Beta strand

30 – 34

5

Sequences

	Sequence		Length	Mass (Da)
	P82228 [UniParc]. Last modified May 30, 2000. Version 1. Checksum: E4DDF046CC750FFC	FASTA	37	3,768
	10 20 30 AICTGADRPC AACCPCCPGT SCKAESNGVS YCRKDEP

References

[1]	"Discovery and characterization of a family of insecticidal neurotoxins with a rare vicinal disulfide bridge." Wang X.-H., Connor M., Smith R., Maciejewski M.W., Howden M.E.H., Nicholson G.M., Christie M.J., King G.F. Nat. Struct. Biol. 7:505-513(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE, FUNCTION, STRUCTURE BY NMR. Tissue: Venom.
[2]	"Scanning mutagenesis of a Janus-faced atracotoxin reveals a bipartite surface patch that is essential for neurotoxic function." Maggio F., King G.F. J. Biol. Chem. 277:22806-22813(2002) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ILE-2; ARG-8; PRO-9; 13-CYS-CYS-14; VAL-29 AND TYR-31, LETHAL DOSE.
[3]	"Role of the structurally disordered N- and C-terminal residues in the Janus-faced atracotoxins." Maggio F., King G.F. Toxicon 40:1355-1361(2002) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ALA-1; 1-ALA-ILE-2 AND 36-GLU-PRO-37, LETHAL DOSE.
[4]	"A model genetic system for testing the in vivo function of peptide toxins." Tedford H.W., Maggio F., Reenan R.A., King G. Peptides 28:51-56(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"Phase coupling of a circadian neuropeptide with rest/activity rhythms detected using a membrane-tethered spider toxin." Wu Y., Cao G., Pavlicek B., Luo X., Nitabach M.N. PLoS Biol. 6:E273-E273(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"The Janus-faced atracotoxins are specific blockers of invertebrate K(Ca) channels." Gunning S.J., Maggio F., Windley M.J., Valenzuela S.M., King G.F., Nicholson G.M. FEBS J. 275:4045-4059(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.

Cross-references

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DL0	NMR	-	A	1-37	[»]

ProteinModelPortal

P82228.

SMR

P82228. Positions 1-37.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ArachnoServer

AS000174. kappa-hexatoxin-Hv1c.

Family and domain databases

InterPro

IPR012499. Toxin_16.
[Graphical view]

Pfam

PF07945. Toxin_16. 1 hit.
[Graphical view]

PROSITE

PS60020. J_ACTX. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P82228.

Entry information

Entry name

TJT1C_HADVE

Accession

Primary (citable) accession number: P82228

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 30, 2000
Last modified:	April 3, 2013
This is version 57 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program