P56852 (TXHN1_GRARO) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Kappa-theraphotoxin-Gr1a Short name=Kappa-TRTX-Gr1a Alternative name(s): Hanatoxin-1 Short name=HaTx1
Organism	Grammostola rosea (Chilean rose tarantula) (Grammostola spatulata)
Taxonomic identifier	432528 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Chelicerata › Arachnida › Araneae › Mygalomorphae › Theraphosidae › Grammostola

Protein attributes

Sequence length	35 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inhibits Kv2.1/KCNB1 and Kv4.2/KCND2 voltage-gated potassium channels. Acts as a gating modifier by shifting channel openings to more depolarized voltages and acts via the occupancy of multiple binding sites on the channel. The toxin binding sites are situated on the S3-S4 extracellular linker of the channel. At least two hanatoxin molecules can occupy the Kv2.1/KCNB1 channel, and maybe more (three or four). Can also inhibit calcium channels (Cav2.1/CACNA1A). Needs to partition into the membrane in order to bind to the channel. Ref.2 Ref.3 Ref.4 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.
Sequence similarities	Belongs to the huwentoxin-1 family.

Ontologies

Keywords
Cellular component	Secreted
Domain	Knottin
Molecular function	Calcium channel inhibitor 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	calcium channel inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW 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 – 35

35

Kappa-theraphotoxin-Gr1a

PRO_0000045012

Regions

Region

4 – 6

3

Involved in active face By similarity

Sites

Site

3

1

May be involved in interaction with voltage sensor By similarity

Site

22

1

May be involved in interaction with voltage sensor By similarity

Site

30

1

Involved in active face By similarity

Amino acid modifications

Disulfide bond

2 ↔ 16

Ref.7

Disulfide bond

9 ↔ 21

Ref.7

Disulfide bond

15 ↔ 28

Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

35

Helix Strand Turn

Details...

Helix

12 – 14

3

Beta strand

17 – 21

5

Turn

23 – 25

3

Beta strand

27 – 30

4

Sequences

	Sequence		Length	Mass (Da)
	P56852 [UniParc]. Last modified May 30, 2000. Version 1. Checksum: D401AC8A9B14DB12	FASTA	35	4,121
	10 20 30 ECRYLFGGCK TTSDCCKHLG CKFRDKYCAW DFTFS

References

[1]	"An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula." Swartz K.J., MacKinnon R. Neuron 15:941-949(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE. Tissue: Venom.
[2]	"Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites." Swartz K.J., MacKinnon R. Neuron 18:665-673(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[3]	"Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels." Swartz K.J., MacKinnon R. Neuron 18:675-682(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[4]	"Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels." Li-Smerin Y., Swartz K.J. Proc. Natl. Acad. Sci. U.S.A. 95:8585-8589(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"Voltage-sensor activation with a tarantula toxin as cargo." Phillips L.R., Milescu M., Li-Smerin Y., Mindell J.A., Kim J.I., Swartz K.J. Nature 436:857-860(2005) [PubMed] [Europe PMC] [Abstract] Cited for: MEMBRANE-PARTITIONING.
[6]	"Gating modifier peptides as probes of pancreatic beta-cell physiology." Herrington J. Toxicon 49:231-238(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION ON PANCREATIC BETA-CELLS.
[7]	"Solution structure of hanatoxin1, a gating modifier of voltage-dependent K(+) channels: common surface features of gating modifier toxins." Takahashi H., Kim J.I., Min H.J., Sato K., Swartz K.J., Shimada I. J. Mol. Biol. 297:771-780(2000) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.

Cross-references

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D1H	NMR	-	A	1-35	[»]

ProteinModelPortal

P56852.

SMR

P56852. Positions 1-35.

ModBase

Search...

Protein family/group databases

TCDB

8.B.5.3.6. Na+/K+/Ca2+ channel targeting tarantula huwentoxin (THT) family.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ArachnoServer

AS000342. kappa-theraphotoxin-Gr1a.

Family and domain databases

InterPro

IPR011696. Ion_channel_inhibitory.
[Graphical view]

Pfam

PF07740. Toxin_12. 1 hit.
[Graphical view]

PROSITE

PS60021. HWTX_1. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P56852.

Entry information

Entry name

TXHN1_GRARO

Accession

Primary (citable) accession number: P56852

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 30, 2000
Last modified:	April 3, 2013
This is version 59 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program