ID   NTA_AVIPU               Reviewed;          36 AA.
AC   P0DQJ6;
DT   11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT   11-DEC-2019, sequence version 1.
DT   25-MAY-2022, entry version 7.
DE   RecName: Full=Mu/kappa-theraphotoxin-Ap1a {ECO:0000303|PubMed:30149017};
DE            Short=Mu/kappa-TRTX-Ap1a {ECO:0000303|PubMed:30149017};
DE   AltName: Full=Avicularia purpurea;
OS   Avicularia purpurea (Ecuadorian purple pinktoe tarantula).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Mygalomorphae; Theraphosidae; Avicularia.
OX   NCBI_TaxID=2652666;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, SYNTHESIS, AMIDATION AT PHE-36, SUBCELLULAR
RP   LOCATION, MASS SPECTROMETRY, AND 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: Inhibitor of voltage-gated potassium and sodium channels.
CC       Among other potassium channels, it selectively inhibits
CC       Kv10.1/KCNH1/EAG1 (IC(50)=236 nM) by shifting the voltage dependence of
CC       channel activation in a depolarising direction, it shows a maximum
CC       inhibition of 80% at saturating concentrations, it shows fast on-rates,
CC       and is poorly reversible. It also slightly affects channel
CC       inactivation, when the membrane is highly depolarised (>+80 mV). It
CC       shows similar potency on Nav1.7/SCN9A (IC(50)=222 nM) and lower potency
CC       on Nav1.2/SCN2A (IC(50)=519 nM). {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:0000305|PubMed:30149017}.
CC   -!- MASS SPECTROMETRY: Mass=4220.077; 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 Nav1.5/SCN5A (IC(50)=2565), and
CC       Kv11.1/KCNH2/ERG1 (IC(50)=8197 nM). {ECO:0000269|PubMed:30149017}.
CC   -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family.
CC       {ECO:0000305}.
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DR   AlphaFoldDB; P0DQJ6; -.
DR   SMR; P0DQJ6; -.
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   Amidation; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Knottin; Pharmaceutical;
KW   Potassium channel impairing toxin; Secreted; Toxin;
KW   Voltage-gated potassium channel impairing toxin.
FT   CHAIN           1..36
FT                   /note="Mu/kappa-theraphotoxin-Ap1a"
FT                   /evidence="ECO:0000269|PubMed:30149017"
FT                   /id="PRO_0000448841"
FT   MOD_RES         36
FT                   /note="Phenylalanine amide"
FT                   /evidence="ECO:0000269|PubMed:30149017"
FT   DISULFID        3..18
FT                   /evidence="ECO:0000250|UniProtKB:A0A3F2YLP5"
FT   DISULFID        10..23
FT                   /evidence="ECO:0000250|UniProtKB:A0A3F2YLP5"
FT   DISULFID        17..30
FT                   /evidence="ECO:0000250|UniProtKB:A0A3F2YLP5"
SQ   SEQUENCE   36 AA;  4230 MW;  A4240EFB7F4DCB2E CRC64;
     GDCHKFWGWC RDEPDPCCEH LTCSTKHGWC VWDGSF