TXHN1_GRARO
ID TXHN1_GRARO Reviewed; 85 AA.
AC P56852; M5AYA3;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 2.
DT 25-MAY-2022, entry version 84.
DE RecName: Full=Kappa-theraphotoxin-Gr1a {ECO:0000305};
DE Short=Kappa-TRTX-Gr1a {ECO:0000305};
DE AltName: Full=Hanatoxin-1;
DE Short=HaTx1;
DE Flags: Precursor;
OS Grammostola rosea (Chilean rose tarantula) (Grammostola spatulata).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Grammostola.
OX NCBI_TaxID=432528;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RA Kimura T., Kubo T.;
RT "Grammostola spatulata venom gland cDNA.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 51-85, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX 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 of a
RT Chilean tarantula.";
RL Neuron 15:941-949(1995).
RN [3]
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 through
RT multiple binding sites.";
RL Neuron 18:665-673(1997).
RN [4]
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 voltage-
RT dependent K+ channels.";
RL Neuron 18:675-682(1997).
RN [5]
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 voltage-
RT gated Ca2+ and K+ channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8585-8589(1998).
RN [6]
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 [7]
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 physiology.";
RL Toxicon 49:231-238(2007).
RN [8]
RP STRUCTURE BY NMR OF 51-85, AND DISULFIDE BONDS.
RX 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-dependent
RT K(+) channels: common surface features of gating modifier toxins.";
RL J. Mol. Biol. 297:771-780(2000).
CC -!- FUNCTION: Inhibits Kv2.1/KCNB1 and Kv4.2/KCND2 voltage-gated potassium
CC channels. Acts as a gating modifier by shifting channel openings to
CC more depolarized voltages and acts via the occupancy of multiple
CC binding sites on the channel. The toxin binding sites are situated on
CC the S3-S4 extracellular linker of the channel. At least two hanatoxin
CC molecules can occupy the Kv2.1/KCNB1 channel, and maybe more (three or
CC four). Can also inhibit calcium channels (Cav2.1/CACNA1A). Needs to
CC partition into the membrane in order to bind to the channel.
CC {ECO:0000269|PubMed:17101164, ECO:0000269|PubMed:9136774,
CC ECO:0000269|PubMed:9136775, ECO:0000269|PubMed:9671721}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7576642}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:7576642}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:10731427}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 09 (HaTx)
CC subfamily. {ECO:0000305}.
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DR EMBL; AB200991; BAN13487.1; -; mRNA.
DR PDB; 1D1H; NMR; -; A=51-85.
DR PDBsum; 1D1H; -.
DR AlphaFoldDB; P56852; -.
DR SMR; P56852; -.
DR TCDB; 8.B.5.3.6; the na(+)/k(+)/ca(2+) channel targeting tarantula huwentoxin (tht) family.
DR ArachnoServer; AS000342; kappa-theraphotoxin-Gr1a.
DR ArachnoServer; AS002037; kappa-theraphotoxin-Gr1e.
DR EvolutionaryTrace; P56852; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR011696; Huwentoxin-1.
DR Pfam; PF07740; Toxin_12; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium channel impairing toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin;
KW Potassium channel impairing toxin; Secreted; Signal; Toxin;
KW Voltage-gated calcium channel impairing toxin;
KW Voltage-gated potassium channel impairing toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..49
FT /evidence="ECO:0000305|PubMed:7576642"
FT /id="PRO_0000452535"
FT PEPTIDE 50..84
FT /note="Kappa-theraphotoxin-Gr1a"
FT /evidence="ECO:0000269|PubMed:7576642"
FT /id="PRO_0000045012"
FT REGION 53..55
FT /note="Involved in active face"
FT /evidence="ECO:0000250"
FT SITE 52
FT /note="May be involved in interaction with voltage sensor"
FT /evidence="ECO:0000250"
FT SITE 71
FT /note="May be involved in interaction with voltage sensor"
FT /evidence="ECO:0000250"
FT SITE 79
FT /note="Involved in active face"
FT /evidence="ECO:0000250"
FT DISULFID 51..65
FT /evidence="ECO:0000269|PubMed:10731427,
FT ECO:0007744|PDB:1D1H"
FT DISULFID 58..70
FT /evidence="ECO:0000269|PubMed:10731427,
FT ECO:0007744|PDB:1D1H"
FT DISULFID 64..77
FT /evidence="ECO:0000269|PubMed:10731427,
FT ECO:0007744|PDB:1D1H"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:1D1H"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:1D1H"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:1D1H"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:1D1H"
SQ SEQUENCE 85 AA; 9528 MW; 23CB3A3819B30970 CRC64;
MKTSVFAAIL GLALFAVLCS GSELQEKDLK ETLLSAIMET ALEAQPEERE CRYLFGGCKT
TSDCCKHLGC KFRDKYCAWD FTFSK
