ID   TX1A_GRAIH              Reviewed;          29 AA.
AC   C0HJJ7;
DT   02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT   02-DEC-2020, sequence version 1.
DT   25-MAY-2022, entry version 4.
DE   RecName: Full=Beta/kappa-theraphotoxin-Gi1a {ECO:0000303|PubMed:32717411};
DE            Short=Beta/kappa-TRTX-Gi1a {ECO:0000303|PubMed:32717411};
DE   AltName: Full=GiTx1 {ECO:0000303|PubMed:32717411};
OS   Grammostola iheringi (Argentinean black tarantula) (Eurypelma iheringii).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Mygalomorphae; Theraphosidae; Grammostola.
OX   NCBI_TaxID=1496261;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY,
RP   3D-STRUCTURE MODELING, LETHAL DOSE, AND BIOASSAY.
RC   TISSUE=Venom;
RX   PubMed=32717411; DOI=10.1016/j.biochi.2020.07.008;
RA   Montandon G.G., Cassoli J.S., Peigneur S., Braga T.V.,
RA   Moreira Dos Santos D., Bittencourt Paiva A.L., Ricardo de Moraes E.,
RA   Kushmerick C., Borges M.H., Richardson M., Monteiro de Castro Pimenta A.,
RA   Kjeldsen F., Vasconcelos Diniz M.R., Tytgat J., Elena de Lima M.;
RT   "GiTx1(beta/kappa-theraphotoxin-Gi1a), a novel toxin from the venom of
RT   Brazilian tarantula Grammostola iheringi (Mygalomorphae, Theraphosidae):
RT   isolation, structural assessments and activity on voltage-gated ion
RT   channels.";
RL   Biochimie 176:138-149(2020).
CC   -!- FUNCTION: Inhibits mammalian and insect voltage-gated sodium and
CC       potassium voltage-gated channels. Inhibits the mammalian sodium
CC       channels rNav1.2/SCN2A, rNav1.3/SCN3A, rNav1.4/SCN4A, hNav1.5/SCN5A,
CC       mNav1.6/SCN8A (IC(50)=156.39 nM), hNav1.8/SCN10A, the arachnid sodium
CC       channel VdNav (IC(50)=124.05 nM), as well as the potassium channels
CC       Kv11.1/KCNH2/ERG1 (IC(50)=3.7 uM) and rKv4.3/KCND3. In vivo, is lethal
CC       on insects (tested on flies M.domestica). When tested on mice, it shows
CC       very low toxicity, causing reversible paralyzes at the first hour after
CC       intracerebroventricular injection. {ECO:0000269|PubMed:32717411}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:32717411}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:32717411}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000250|UniProtKB:P83476}.
CC   -!- MASS SPECTROMETRY: Mass=3585.2; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:32717411};
CC   -!- TOXIC DOSE: LD(50) is 20.9 mg/kg by intrathoracic injections into adult
CC       house flies (Musca domestica). {ECO:0000269|PubMed:32717411}.
CC   -!- MISCELLANEOUS: This toxin does not inhibit the potassium channels
CC       Shaker-IR (with inactivation domain removed) and the rat Kv2.1/KCNB1.
CC       {ECO:0000269|PubMed:32717411}.
CC   -!- SIMILARITY: Belongs to the phrixotoxin family. {ECO:0000305}.
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DR   AlphaFoldDB; C0HJJ7; -.
DR   SMR; C0HJJ7; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Knottin; Neurotoxin; Potassium channel impairing toxin; Secreted; Toxin;
KW   Voltage-gated potassium channel impairing toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   PEPTIDE         1..29
FT                   /note="Beta/kappa-theraphotoxin-Gi1a"
FT                   /evidence="ECO:0000269|PubMed:32717411"
FT                   /id="PRO_0000451459"
FT   DISULFID        2..16
FT                   /evidence="ECO:0000250|UniProtKB:P83476"
FT   DISULFID        9..21
FT                   /evidence="ECO:0000250|UniProtKB:P83476"
FT   DISULFID        15..25
FT                   /evidence="ECO:0000250|UniProtKB:P83476"
SQ   SEQUENCE   29 AA;  3594 MW;  E4FDA646A9BB313C CRC64;
     SCQKWMWTCD QKRPCCEDMV CKLWCKIIK