true
2000-05-30
2008-07-22
44
TXHN1_GRARO
TX1_GRASP
TXHN1_GRASP
Hanatoxin-1
HaTx1
An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula.
Swartz K.J.
MacKinnon R.
doi:10.1016/0896-6273(95)90184-1
1995
Neuron
15
941-949
PROTEIN SEQUENCE
Venom
Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites.
Swartz K.J.
MacKinnon R.
doi:10.1016/S0896-6273(00)80306-2
1997
Neuron
18
665-673
FUNCTION
Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels.
Swartz K.J.
MacKinnon R.
doi:10.1016/S0896-6273(00)80307-4
1997
Neuron
18
675-682
FUNCTION
Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels.
Li-Smerin Y.
Swartz K.J.
doi:10.1073/pnas.95.15.8585
1998
Proc. Natl. Acad. Sci. U.S.A.
95
8585-8589
FUNCTION
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.
doi:10.1038/nature03873
2005
Nature
436
857-860
MEMBRANE-PARTITIONING
Gating modifier peptides as probes of pancreatic beta-cell physiology.
Herrington J.
doi:10.1016/j.toxicon.2006.09.012
2007
Toxicon
49
231-238
FUNCTION ON PANCREATIC BETA-CELLS
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.
doi:10.1006/jmbi.2000.3609
2000
J. Mol. Biol.
297
771-780
STRUCTURE BY NMR
DISULFIDE BONDS
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 channel, and maybe more (three or four). Can also inhibit calcium channels (Cav2.1 / CACNA1A). Need to partition into the membrane in order to bind to the channel.
Expressed by the venom gland.
The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.
Blockers of Kv2.1 potassium channels, such as hanatoxin, may be a useful approach to the design of novel therapeutic agents for the treatment of type 2 diabetes.
Belongs to the huwentoxin-1 superfamily. Hanatoxin family.
Hanatoxin-1
1
35
Involved in active face
4
6
May be involved in interaction with voltage sensor
3
3
May be involved in interaction with voltage sensor
22
22
Involved in active face
30
30
2
2
16
16
9
9
21
21
15
15
28
28
12
14
17
21
23
25
27
30
PDB
A=1-35
PDBsum
InterPro
Toxin_12
Pfam
Toxin_12
1
2000-05-30
1
4121
ECRYLFGGCK TTSDCCKHLG CKFRDKYCAW DFTFS