ID   NTA_AVIAU               Reviewed;          36 AA.
AC   A0A3F2YLP5;
DT   11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT   11-DEC-2019, sequence version 2.
DT   25-MAY-2022, entry version 13.
DE   RecName: Full=Kappa-theraphotoxin-Aa1a {ECO:0000303|PubMed:30149017};
DE            Short=Kappa-TRTX-Aa1a {ECO:0000303|PubMed:30149017};
DE   AltName: Full=Avicularia aurantiaca;
OS   Avicularia aurantiaca (Yellow-banded pinktoe tarantula).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Mygalomorphae; Theraphosidae; Avicularia.
OX   NCBI_TaxID=2652665;
RN   [1]
RP   PROTEIN SEQUENCE, STRUCTURE BY NMR, FUNCTION, SYNTHESIS, DISULFIDE BOND,
RP   AMIDATION AT ILE-36, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND
RP   PHARMACEUTICAL.
RC   TISSUE=Venom;
RX   PubMed=30149017; DOI=10.1016/j.bcp.2018.08.038;
RA   Ma L., Chin Y.K.Y., Dekan Z., Herzig V., Chow C.Y., Heighway J., Lam S.W.,
RA   Guillemin G.J., Alewood P.F., King G.F.;
RT   "Novel venom-derived inhibitors of the human EAG channel, a putative
RT   antiepileptic drug target.";
RL   Biochem. Pharmacol. 158:60-72(2018).
CC   -!- FUNCTION: Selective inhibitor of voltage-gated potassium channel
CC       Kv10.1/KCNH1/EAG1 (IC(50)=637 nM). It acts by shifting the voltage
CC       dependence of channel activation in a depolarising direction. It shows
CC       a 100% inhibition at saturating concentrations, shows fast on-rates and
CC       is reversible. It also slightly affects channel inactivation, when the
CC       membrane is highly depolarised (>+80 mV).
CC       {ECO:0000269|PubMed:30149017}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:30149017}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:30149017}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000269|PubMed:30149017}.
CC   -!- MASS SPECTROMETRY: Mass=4148.217; Method=MALDI; Note=Monoisotopic
CC       mass.; Evidence={ECO:0000269|PubMed:30149017};
CC   -!- PHARMACEUTICAL: Could be used as informative lead for the development
CC       of novel antiepileptic drugs, as well as pharmacological tool for
CC       probing Kv10.1/KCNH1/EAG1 function. {ECO:0000305|PubMed:30149017}.
CC   -!- MISCELLANEOUS: Weakly inhibits Nav1.2/SCN2A (IC(50)=1449 nM),
CC       Nav1.7/SCN9A (IC(50)=1528 nM), Nav1.5/SCN5A (IC(50)=7316), and
CC       Kv11.1/KCNH2/ERG1 (IC(50)=8511 nM). {ECO:0000269|PubMed:30149017}.
CC   -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family.
CC       {ECO:0000305}.
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DR   PDB; 5WLX; NMR; -; A=1-36.
DR   PDBsum; 5WLX; -.
DR   AlphaFoldDB; A0A3F2YLP5; -.
DR   BMRB; A0A3F2YLP5; -.
DR   SMR; A0A3F2YLP5; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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; Amidation; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Pharmaceutical;
KW   Potassium channel impairing toxin; Secreted; Toxin;
KW   Voltage-gated potassium channel impairing toxin.
FT   CHAIN           1..36
FT                   /note="Kappa-theraphotoxin-Aa1a"
FT                   /evidence="ECO:0000269|PubMed:30149017"
FT                   /id="PRO_0000448842"
FT   MOD_RES         36
FT                   /note="Isoleucine amide"
FT                   /evidence="ECO:0000269|PubMed:30149017"
FT   DISULFID        3..18
FT                   /evidence="ECO:0000269|PubMed:30149017,
FT                   ECO:0007744|PDB:5WLX"
FT   DISULFID        10..23
FT                   /evidence="ECO:0000269|PubMed:30149017,
FT                   ECO:0007744|PDB:5WLX"
FT   DISULFID        17..30
FT                   /evidence="ECO:0000269|PubMed:30149017,
FT                   ECO:0007744|PDB:5WLX"
FT   TURN            25..27
FT                   /evidence="ECO:0007829|PDB:5WLX"
SQ   SEQUENCE   36 AA;  4158 MW;  B5802DF9E8E06B84 CRC64;
     GDCHKFLGWC RGEKDPCCEH LTCHVKHGWC VWDGTI