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UniProtKB/Swiss-Prot entry P56852


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name TXHN1_GRARO
Primary accession number P56852
Secondary accession numbers None
Integrated into Swiss-Prot on May 30, 2000
Sequence was last modified on May 30, 2000 (Sequence version 1)
Annotations were last modified on    July 22, 2008 (Entry version 44)
Name and origin of the protein
Protein name Hanatoxin-1
Synonym HaTx1
Gene name None
From
Grammostola rosea (Chilean rose tarantula) (Grammostola spatulata) [TaxID: 432528] 
Taxonomy Eukaryota; Metazoa; Arthropoda; Chelicerata; Arachnida; Araneae; Mygalomorphae; Theraphosidae; Grammostola.
Protein existence 1: Evidence at protein level;
References
[1]
PROTEIN SEQUENCE.
TISSUE=Venom;
DOI=10.1016/0896-6273(95)90184-1; PubMed=7576642 [NCBI, ExPASy, EBI, Israel, Japan]
Swartz K.J., MacKinnon R.;
"An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula.";
Neuron 15:941-949(1995).
[2]
FUNCTION.
DOI=10.1016/S0896-6273(00)80306-2; PubMed=9136774 [NCBI, ExPASy, EBI, Israel, Japan]
Swartz K.J., MacKinnon R.;
"Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites.";
Neuron 18:665-673(1997).
[3]
FUNCTION.
DOI=10.1016/S0896-6273(00)80307-4; PubMed=9136775 [NCBI, ExPASy, EBI, Israel, Japan]
Swartz K.J., MacKinnon R.;
"Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels.";
Neuron 18:675-682(1997).
[4]
FUNCTION.
DOI=10.1073/pnas.95.15.8585; PubMed=9671721 [NCBI, ExPASy, EBI, Israel, Japan]
Li-Smerin Y., Swartz K.J.;
"Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels.";
Proc. Natl. Acad. Sci. U.S.A. 95:8585-8589(1998).
[5]
MEMBRANE-PARTITIONING.
DOI=10.1038/nature03873; PubMed=16094370 [NCBI, ExPASy, EBI, Israel, Japan]
Phillips L.R., Milescu M., Li-Smerin Y., Mindell J.A., Kim J.I., Swartz K.J.;
"Voltage-sensor activation with a tarantula toxin as cargo.";
Nature 436:857-860(2005).
[6]
FUNCTION ON PANCREATIC BETA-CELLS.
DOI=10.1016/j.toxicon.2006.09.012; PubMed=17101164 [NCBI, ExPASy, EBI, Israel, Japan]
Herrington J.;
"Gating modifier peptides as probes of pancreatic beta-cell physiology.";
Toxicon 49:231-238(2007).
[7]
STRUCTURE BY NMR, AND DISULFIDE BONDS.
DOI=10.1006/jmbi.2000.3609; PubMed=10731427 [NCBI, ExPASy, EBI, Israel, Japan]
Takahashi H., Kim J.I., Min H.J., Sato K., Swartz K.J., Shimada I.;
"Solution structure of hanatoxin1, a gating modifier of voltage-dependent K(+) channels: common surface features of gating modifier toxins.";
J. Mol. Biol. 297:771-780(2000).
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 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.
  • 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.
  • MISCELLANEOUS: 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.
  • SIMILARITY: Belongs to the huwentoxin-1 superfamily. Hanatoxin family.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
3D structure databases
PDB
1D1H; NMR; -; A=1-35.[ExPASy / RCSB / EBI]
PDBsum 1D1H; -.
ModBase P56852.
Family and domain databases
InterPro IPR011696; Toxin_12.
Graphical view of domain structure.
Pfam PF07740; Toxin_12; 1.
Pfam graphical view of domain structure.
BLOCKS P56852.
Other
ProtoNet P56852.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Calcium channel inhibitor; Direct protein sequencing; Ionic channel inhibitor; Knottin; Neurotoxin; Potassium channel inhibitor; Secreted; Toxin.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom  To Length Description FTId
PEPTIDE   1   35  35     Hanatoxin-1. PRO_0000045012
REGION   4    6  3     Involved in active face (By similarity). 
SITE   3    3  1     May be involved in interaction with voltage sensor (By similarity). 
SITE   22   22  1     May be involved in interaction with voltage sensor (By similarity). 
SITE   30   30  1     Involved in active face (By similarity). 
DISULFID   2   16         
DISULFID   9   21         
DISULFID   15   28         
HELIX   12   14  3      
STRAND   17   21  5      
TURN   23   25  3      
STRAND   27   30  4      
Sequence information
Length: 35 AA [This is the length of the unprocessed precursor] Molecular weight: 4121 Da [This is the MW of the unprocessed precursor] CRC64: D401AC8A9B14DB12 [This is a checksum on the sequence]
        10         20         30 
ECRYLFGGCK TTSDCCKHLG CKFRDKYCAW DFTFS 

P56852 in FASTA format

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