ID   KAX6D_HETSP             Reviewed;          34 AA.
AC   P84094;
DT   05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   05-SEP-2006, sequence version 1.
DT   25-MAY-2022, entry version 54.
DE   RecName: Full=Potassium channel toxin alpha-KTx 6.13;
DE   AltName: Full=Spinoxin {ECO:0000303|Ref.1, ECO:0000303|Ref.2};
OS   Heterometrus spinifer (Asia giant forest scorpion) (Malaysian black
OS   scorpion).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Iurida; Scorpionoidea; Scorpionidae; Heterometrinae;
OC   Heterometrus.
OX   NCBI_TaxID=118530;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, AND AMIDATION AT CYS-34.
RC   TISSUE=Venom;
RA   Nirthanan S., Huys I., Sugahara Y., Gopalakrishnakone P., Sato K.,
RA   Tytgat J.;
RL   Submitted (JUL-2004) to UniProtKB.
RN   [2]
RP   SYNTHESIS, AND FUNCTION.
RA   Sugahara Y., Nirthanan S., Huys I., Kobayashi K., Kohno T., Tytgat J.,
RA   Gopalakrishnakone P., Sato K.;
RT   "Synthesis and characterization of spinoxin, a novel peptide toxin from the
RT   Malaysian black scorpion.";
RL   (In) Ueki M. (eds.);
RL   Peptide science 2003 - The Proceedings of the 40th Symposium on Japanese
RL   peptide symposium, pp.283-284, Protein Research Foundation, Osaka (2004).
RN   [3]
RP   PHARMACOLOGICAL CHARACTERIZATION.
RX   PubMed=18687312; DOI=10.1016/j.bcp.2008.07.008;
RA   Abdel-Mottaleb Y., Corzo G., Martin-Eauclaire M.F., Satake H., Ceard B.,
RA   Peigneur S., Nambaru P., Bougis P.E., Possani L.D., Tytgat J.;
RT   "A common 'hot spot' confers hERG blockade activity to alpha-scorpion
RT   toxins affecting K+ channels.";
RL   Biochem. Pharmacol. 76:805-815(2008).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND DISULFIDE BONDS.
RA   Nirthanan S., Yamaguchi Y., Sugahara Y., Peigneur S., Nose T.,
RA   Kobayashi K., Kohno T., Gopalakrishnakone P., Sato K., Tytgat J.;
RT   "Delineating a potassium channel blocking mini-peptide from spinoxin
RT   (alphaKTx6.13), a new Kv1 channel toxin from Heterometrus spinifer scorpion
RT   venom.";
RL   Submitted (MAY-2016) to UniProtKB.
RN   [5]
RP   FUNCTION, AND SYNTHESIS.
RX   PubMed=31276191; DOI=10.1002/1873-3468.13530;
RA   Kasheverov I.E., Oparin P.B., Zhmak M.N., Egorova N.S., Ivanov I.A.,
RA   Gigolaev A.M., Nekrasova O.V., Serebryakova M.V., Kudryavtsev D.S.,
RA   Prokopev N.A., Hoang A.N., Tsetlin V.I., Vassilevski A.A., Utkin Y.N.;
RT   "Scorpion toxins interact with nicotinic acetylcholine receptors.";
RL   FEBS Lett. 593:2779-2789(2019).
CC   -!- FUNCTION: Antagonist of Kv1/KCNA potassium channels (Ref.1, Ref.2).
CC       Shows a weak interaction with muscle-type nicotinic acetylcholine
CC       receptors (nAChR), since it inhibits alpha-bungarotoxin binding to both
CC       muscle-type nAChR from T.californica (IC(50)=490 nM) (PubMed:31276191).
CC       This suggests it probably weakly inhibits nAChR (PubMed:31276191).
CC       {ECO:0000269|PubMed:31276191, ECO:0000269|Ref.1, ECO:0000269|Ref.2}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.1}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC   -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to a
CC       beta-sheet by disulfide bonds (CSalpha/beta).
CC   -!- MISCELLANEOUS: Does not inhibit ERG1/Kv11.1/KCNH2 potassium channels
CC       (PubMed:18687312). May not inhibit neuronal human alpha-7 nAChR, since
CC       it does not inhibit alpha-7 alpha-bungarotoxin binding (IC(50)>>20 uM)
CC       (PubMed:31276191). {ECO:0000269|PubMed:18687312,
CC       ECO:0000269|PubMed:31276191}.
CC   -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC       channel inhibitor family. Alpha-KTx 06 subfamily. {ECO:0000305}.
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DR   AlphaFoldDB; P84094; -.
DR   SMR; P84094; -.
DR   EvolutionaryTrace; P84094; -.
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   Gene3D; 3.30.30.10; -; 1.
DR   InterPro; IPR036574; Scorpion_toxin-like_sf.
DR   InterPro; IPR001947; Scorpion_toxinS_K_inh.
DR   Pfam; PF00451; Toxin_2; 1.
DR   SUPFAM; SSF57095; SSF57095; 1.
DR   PROSITE; PS01138; SCORP_SHORT_TOXIN; 1.
PE   1: Evidence at protein level;
KW   Amidation; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Neurotoxin; Potassium channel impairing toxin;
KW   Secreted; Toxin; Voltage-gated potassium channel impairing toxin.
FT   CHAIN           1..34
FT                   /note="Potassium channel toxin alpha-KTx 6.13"
FT                   /evidence="ECO:0000269|Ref.1"
FT                   /id="PRO_0000248273"
FT   SITE            23
FT                   /note="Basic residue of the functional dyad"
FT                   /evidence="ECO:0000250|UniProtKB:Q10726"
FT   SITE            32
FT                   /note="Aromatic residue of the functional dyad"
FT                   /evidence="ECO:0000250|UniProtKB:Q10726"
FT   MOD_RES         34
FT                   /note="Cysteine amide"
FT                   /evidence="ECO:0000269|Ref.1"
FT   DISULFID        3..24
FT                   /evidence="ECO:0000269|Ref.4"
FT   DISULFID        9..29
FT                   /evidence="ECO:0000269|Ref.4"
FT   DISULFID        13..31
FT                   /evidence="ECO:0000269|Ref.4"
FT   DISULFID        19..34
FT                   /evidence="ECO:0000269|Ref.4"
SQ   SEQUENCE   34 AA;  3709 MW;  BE9142E067B6BD26 CRC64;
     IRCSGSRDCY SPCMKQTGCP NAKCINKSCK CYGC