ID   KA211_TITSE             Reviewed;          63 AA.
AC   P86270; A0A218QXC6; A0A7S8MV48;
DT   26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT   03-AUG-2022, sequence version 2.
DT   03-AUG-2022, entry version 30.
DE   RecName: Full=Potassium channel toxin alpha-KTx 21.1 {ECO:0000303|PubMed:21600910};
DE   AltName: Full=Tityustoxin-15 {ECO:0000305|PubMed:21600910};
DE            Short=Ts15 {ECO:0000303|PubMed:21600910};
DE   Flags: Precursor;
OS   Tityus serrulatus (Brazilian scorpion).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Tityus.
OX   NCBI_TaxID=6887;
RN   [1] {ECO:0000312|EMBL:JAW07003.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Telson;
RX   PubMed=29561852; DOI=10.1371/journal.pone.0193739;
RA   de Oliveira U.C., Nishiyama M.Y. Jr., Dos Santos M.B.V.,
RA   Santos-da-Silva A.P., Chalkidis H.M., Souza-Imberg A., Candido D.M.,
RA   Yamanouye N., Dorce V.A.C., Junqueira-de-Azevedo I.L.M.;
RT   "Proteomic endorsed transcriptomic profiles of venom glands from Tityus
RT   obscurus and T. serrulatus scorpions.";
RL   PLoS ONE 13:e0193739-e0193739(2018).
RN   [2] {ECO:0000312|EMBL:QPD99020.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Telson;
RX   PubMed=33181162; DOI=10.1016/j.toxicon.2020.11.001;
RA   Kalapothakis Y., Miranda K., Pereira A.H., Witt A.S.A., Marani C.,
RA   Martins A.P., Leal H.G., Campos-Junior E., Pimenta A.M.C., Borges A.,
RA   Chavez-Olortegui C., Kalapothakis E.;
RT   "Novel components of Tityus serrulatus venom: a transcriptomic approach.";
RL   Toxicon 189:91-104(2021).
RN   [3]
RP   PROTEIN SEQUENCE OF 28-63, FUNCTION, SUBCELLULAR LOCATION, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Venom;
RX   PubMed=21600910; DOI=10.1016/j.toxicon.2011.05.001;
RA   Cologna C.T., Peigneur S., Rosa J.C., Selistre-de-Araujo H.S.,
RA   Varanda W.A., Tytgat J., Arantes E.C.;
RT   "Purification and characterization of Ts15, the first member of a new
RT   alpha-KTX subfamily from the venom of the Brazilian scorpion Tityus
RT   serrulatus.";
RL   Toxicon 58:54-61(2011).
RN   [4]
RP   PROTEIN SEQUENCE OF 49-63, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   TISSUE=Venom;
RX   PubMed=23731212; DOI=10.1021/pr4003068;
RA   Verano-Braga T., Dutra A.A., Leon I.R., Melo-Braga M.N., Roepstorff P.,
RA   Pimenta A.M., Kjeldsen F.;
RT   "Moving pieces in a venomic puzzle: unveiling post-translationally modified
RT   toxins from Tityus serrulatus.";
RL   J. Proteome Res. 12:3460-3470(2013).
RN   [5]
RP   PROTEIN SEQUENCE OF 34-39, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=25199494; DOI=10.1016/j.toxicon.2014.08.064;
RA   Pucca M.B., Amorim F.G., Cerni F.A., Bordon K.C.F., Cardoso I.A.,
RA   Anjolette F.A., Arantes E.C.;
RT   "Influence of post-starvation extraction time and prey-specific diet in
RT   Tityus serrulatus scorpion venom composition and hyaluronidase activity.";
RL   Toxicon 90:326-336(2014).
CC   -!- FUNCTION: Reversibly and voltage-independently blocks voltage-gated
CC       potassium channels rKv1.2/KCNA2 (73%) (IC(50)=196 nM), hKv1.3/KCNA3
CC       (50%) (IC(50)=508 nM), Shaker IR (30%), rKv1.6/KCNA6 (22%) (at 0.5 uM).
CC       Interaction of Ts15 with Kv1.3/KCNA3 is stronger than its interaction
CC       with Kv1.2/KCNA2. {ECO:0000269|PubMed:21600910}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21600910,
CC       ECO:0000269|PubMed:23731212, ECO:0000269|PubMed:25199494}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:25199494}.
CC   -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to
CC       antiparallel beta-sheets by disulfide bonds (CS-alpha/beta).
CC       {ECO:0000305}.
CC   -!- MASS SPECTROMETRY: Mass=3956; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:21600910};
CC   -!- MISCELLANEOUS: Does not block voltage-gated sodium channels
CC       rNav1.4/SCN4A, hNav1.5/SCN5A, mNav1.6/SCN8A and rNav1.8/SCN10A, and
CC       Kv1.1/KCNA1, rKv1.4/KCNA4, rKv1.5/KCNA5, rKv2.1/KCNB1, hKv3.1/KCNC1,
CC       rKv4.2/KCND2, rKv4.3/KCND3 and hERG potassium channels, when tested at
CC       a concentration of 0.5 uM. {ECO:0000305|PubMed:21600910}.
CC   -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC       channel inhibitor family. Alpha-KTx 21 subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=JAW07003.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; GEUW01000042; JAW07003.1; ALT_INIT; mRNA.
DR   EMBL; MT081338; QPD99020.1; -; mRNA.
DR   AlphaFoldDB; P86270; -.
DR   SMR; P86270; -.
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:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Neurotoxin; Potassium channel impairing toxin; Secreted; Signal; Toxin;
KW   Voltage-gated potassium channel impairing toxin.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000255"
FT   PEPTIDE         28..63
FT                   /note="Potassium channel toxin alpha-KTx 21.1"
FT                   /evidence="ECO:0000269|PubMed:21600910"
FT                   /id="PRO_0000376048"
FT   DISULFID        33..53
FT                   /evidence="ECO:0000250|UniProtKB:Q8I0L5"
FT   DISULFID        38..58
FT                   /evidence="ECO:0000250|UniProtKB:Q8I0L5"
FT   DISULFID        42..60
FT                   /evidence="ECO:0000250|UniProtKB:Q8I0L5"
SQ   SEQUENCE   63 AA;  7007 MW;  710816BD7B1DFB6D CRC64;
     MQFSGVVLIL ISMTLVNFVF FETKVEAGKF GKCKPNICAK TCQTEKGKGM GYCNKTECVC
     SEW