ID   KEX12_TITSE             Reviewed;          68 AA.
AC   P0C175; A0A7S8RFW0;
DT   21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2006, sequence version 1.
DT   03-AUG-2022, entry version 43.
DE   RecName: Full=Potassium channel toxin epsilon-KTx 1.2 {ECO:0000303|PubMed:27706049};
DE   AltName: Full=Tityustoxin-12 {ECO:0000305};
DE            Short=Ts12 {ECO:0000303|PubMed:19689419};
DE   AltName: Full=TsPep2 {ECO:0000303|PubMed:12589824};
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]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 27-55, AMIDATION AT TYR-55,
RP   SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RC   TISSUE=Venom;
RX   PubMed=12589824; DOI=10.1016/s0006-291x(03)00082-2;
RA   Pimenta A.M.C., Legros C., Almeida F.M., Mansuelle P., De Lima M.E.,
RA   Bougis P.E., Martin-Eauclaire M.-F.;
RT   "Novel structural class of four disulfide-bridged peptides from Tityus
RT   serrulatus venom.";
RL   Biochem. Biophys. Res. Commun. 301:1086-1092(2003).
RN   [2] {ECO:0000312|EMBL:QPD99050.1}
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   FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND NOMENCLATURE.
RC   TISSUE=Venom;
RX   PubMed=27706049; DOI=10.3390/toxins8100288;
RA   Cremonez C.M., Maiti M., Peigneur S., Cassoli J.S., Dutra A.A.,
RA   Waelkens E., Lescrinier E., Herdewijn P., de Lima M.E., Pimenta A.M.,
RA   Arantes E.C., Tytgat J.;
RT   "Structural and functional elucidation of peptide Ts11 shows evidence of a
RT   novel subfamily of scorpion venom toxins.";
RL   Toxins 8:1-14(2016).
RN   [4]
RP   NOMENCLATURE.
RX   PubMed=19689419; DOI=10.2174/092986609788923329;
RA   Cologna C.T., Marcussi S., Giglio J.R., Soares A.M., Arantes E.C.;
RT   "Tityus serrulatus scorpion venom and toxins: an overview.";
RL   Protein Pept. Lett. 16:920-932(2009).
CC   -!- FUNCTION: Potassium channel blocker. At 3 uM, this toxin blocks
CC       voltage-gated potassium channels rKv1.2/KCNA2 (5%), hKv1.3/KCNA3
CC       (10%),rKv1.4/KCNA4 (20%), Kv11/hERG (24%), and Shaker-IR (27%).
CC       {ECO:0000269|PubMed:27706049}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12589824,
CC       ECO:0000269|PubMed:27706049}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000250|UniProtKB:P0C174}.
CC   -!- DOMAIN: Is completely devoid of the classical secondary structure
CC       elements (alpha-helix and/or beta-strand).
CC       {ECO:0000250|UniProtKB:P0C174}.
CC   -!- MASS SPECTROMETRY: Mass=2993.71; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:12589824};
CC   -!- MASS SPECTROMETRY: Mass=2991.3; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:27706049};
CC   -!- MISCELLANEOUS: Does not block voltage-gated potassium channel
CC       rKv1.1/KCNA1, rKv1.5/KCNA5, and rKv1.6/KCNA6.
CC       {ECO:0000269|PubMed:27706049}.
CC   -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC       channel inhibitor family. Epsilon-KTx 01 subfamily. {ECO:0000305}.
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DR   EMBL; MT450714; QPD99050.1; -; mRNA.
DR   AlphaFoldDB; P0C175; -.
DR   SMR; P0C175; -.
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.
DR   InterPro; IPR036574; Scorpion_toxin-like_sf.
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; Knottin; Potassium channel impairing toxin;
KW   Secreted; Signal; Toxin; Voltage-gated potassium channel impairing toxin.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000305|PubMed:12589824"
FT   PEPTIDE         27..55
FT                   /note="Potassium channel toxin epsilon-KTx 1.2"
FT                   /evidence="ECO:0000269|PubMed:12589824"
FT                   /id="PRO_0000227820"
FT   PROPEP          57..68
FT                   /evidence="ECO:0000305|PubMed:12589824"
FT                   /id="PRO_0000227821"
FT   MOD_RES         55
FT                   /note="Tyrosine amide"
FT                   /evidence="ECO:0000305|PubMed:12589824"
FT   DISULFID        30..38
FT                   /evidence="ECO:0000250|UniProtKB:P0C174"
FT   DISULFID        33..54
FT                   /evidence="ECO:0000250|UniProtKB:P0C174"
FT   DISULFID        37..47
FT                   /evidence="ECO:0000250|UniProtKB:P0C174"
FT   DISULFID        42..52
FT                   /evidence="ECO:0000250|UniProtKB:P0C174"
SQ   SEQUENCE   68 AA;  7435 MW;  FEF23172A7BC6A3C CRC64;
     MKFSCGFLLI FLVLSAMIAT FSEVEATVKC GGCNRKCCAG GCRSGKCING KCQCYGRSDL
     NEEFENYQ