ID   TXHN1_GRARO             Reviewed;          35 AA.
AC   P56852;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 1.
DT   22-JUL-2008, entry version 44.
DE   RecName: Full=Hanatoxin-1;
DE            Short=HaTx1;
OS   Grammostola rosea (Chilean rose tarantula) (Grammostola spatulata).
OC   Eukaryota; Metazoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Mygalomorphae; Theraphosidae; Grammostola.
OX   NCBI_TaxID=432528;
RN   [1]
RP   PROTEIN SEQUENCE.
RC   TISSUE=Venom;
RX   MEDLINE=96049141; PubMed=7576642; DOI=10.1016/0896-6273(95)90184-1;
RA   Swartz K.J., MacKinnon R.;
RT   "An inhibitor of the Kv2.1 potassium channel isolated from the venom
RT   of a Chilean tarantula.";
RL   Neuron 15:941-949(1995).
RN   [2]
RP   FUNCTION.
RX   PubMed=9136774; DOI=10.1016/S0896-6273(00)80306-2;
RA   Swartz K.J., MacKinnon R.;
RT   "Hanatoxin modifies the gating of a voltage-dependent K+ channel
RT   through multiple binding sites.";
RL   Neuron 18:665-673(1997).
RN   [3]
RP   FUNCTION.
RX   PubMed=9136775; DOI=10.1016/S0896-6273(00)80307-4;
RA   Swartz K.J., MacKinnon R.;
RT   "Mapping the receptor site for hanatoxin, a gating modifier of
RT   voltage-dependent K+ channels.";
RL   Neuron 18:675-682(1997).
RN   [4]
RP   FUNCTION.
RX   PubMed=9671721; DOI=10.1073/pnas.95.15.8585;
RA   Li-Smerin Y., Swartz K.J.;
RT   "Gating modifier toxins reveal a conserved structural motif in
RT   voltage-gated Ca2+ and K+ channels.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:8585-8589(1998).
RN   [5]
RP   MEMBRANE-PARTITIONING.
RX   PubMed=16094370; DOI=10.1038/nature03873;
RA   Phillips L.R., Milescu M., Li-Smerin Y., Mindell J.A., Kim J.I.,
RA   Swartz K.J.;
RT   "Voltage-sensor activation with a tarantula toxin as cargo.";
RL   Nature 436:857-860(2005).
RN   [6]
RP   FUNCTION ON PANCREATIC BETA-CELLS.
RX   PubMed=17101164; DOI=10.1016/j.toxicon.2006.09.012;
RA   Herrington J.;
RT   "Gating modifier peptides as probes of pancreatic beta-cell
RT   physiology.";
RL   Toxicon 49:231-238(2007).
RN   [7]
RP   STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX   MEDLINE=20198324; PubMed=10731427; DOI=10.1006/jmbi.2000.3609;
RA   Takahashi H., Kim J.I., Min H.J., Sato K., Swartz K.J., Shimada I.;
RT   "Solution structure of hanatoxin1, a gating modifier of voltage-
RT   dependent K(+) channels: common surface features of gating modifier
RT   toxins.";
RL   J. Mol. Biol. 297:771-780(2000).
CC   -!- FUNCTION: Inhibits Kv2.1 (KCNB1) and Kv4.2 (KCND2) voltage-gated
CC       potassium channels. Acts as a gating modifier by shifting channel
CC       openings to more depolarized voltages and acts via the occupancy
CC       of multiple binding sites on the channel. The toxin binding sites
CC       are situated on the S3-S4 extracellular linker of the channel. At
CC       least two hanatoxin molecules can occupy the Kv2.1 channel, and
CC       maybe more (three or four). Can also inhibit calcium channels
CC       (Cav2.1 / CACNA1A). Need to partition into the membrane in order
CC       to bind to the channel.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC   -!- MISCELLANEOUS: Blockers of Kv2.1 potassium channels, such as
CC       hanatoxin, may be a useful approach to the design of novel
CC       therapeutic agents for the treatment of type 2 diabetes.
CC   -!- SIMILARITY: Belongs to the huwentoxin-1 superfamily. Hanatoxin
CC       family.
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DR   PDB; 1D1H; NMR; -; A=1-35.
DR   PDBsum; 1D1H; -.
DR   InterPro; IPR011696; Toxin_12.
DR   Pfam; PF07740; Toxin_12; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Calcium channel inhibitor; Direct protein sequencing;
KW   Ionic channel inhibitor; Knottin; Neurotoxin;
KW   Potassium channel inhibitor; Secreted; Toxin.
FT   PEPTIDE       1     35       Hanatoxin-1.
FT                                /FTId=PRO_0000045012.
FT   REGION        4      6       Involved in active face (By similarity).
FT   SITE          3      3       May be involved in interaction with
FT                                voltage sensor (By similarity).
FT   SITE         22     22       May be involved in interaction with
FT                                voltage sensor (By similarity).
FT   SITE         30     30       Involved in active face (By similarity).
FT   DISULFID      2     16
FT   DISULFID      9     21
FT   DISULFID     15     28
FT   HELIX        12     14
FT   STRAND       17     21
FT   TURN         23     25
FT   STRAND       27     30
SQ   SEQUENCE   35 AA;  4121 MW;  D401AC8A9B14DB12 CRC64;
     ECRYLFGGCK TTSDCCKHLG CKFRDKYCAW DFTFS
//