ID   KAX41_TITSE             Reviewed;          59 AA.
AC   P46114; A0A7S8MUA9; P08816;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   03-AUG-2022, sequence version 2.
DT   22-FEB-2023, entry version 103.
DE   RecName: Full=Potassium channel toxin alpha-KTx 4.1 {ECO:0000303|PubMed:24590385};
DE   AltName: Full=TSK4 {ECO:0000303|PubMed:7509073};
DE   AltName: Full=Tityustoxin K-alpha {ECO:0000303|PubMed:7509073};
DE            Short=TsTX-K-alpha {ECO:0000303|PubMed:7509073};
DE            Short=TyKalpha {ECO:0000305};
DE   AltName: Full=Tityustoxin-7 {ECO:0000305};
DE            Short=Ts7 {ECO:0000303|PubMed:24590385};
DE   AltName: Full=Toxin II-9;
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:QPD99046.1}
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   [2]
RP   PROTEIN SEQUENCE OF 23-59, FUNCTION, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=7509073; DOI=10.1073/pnas.91.4.1475;
RA   Rogowski R.S., Krueger B.K., Collins J.H., Blaustein M.P.;
RT   "Tityustoxin K alpha blocks voltage-gated noninactivating K+ channels and
RT   unblocks inactivating K+ channels blocked by alpha-dendrotoxin in
RT   synaptosomes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:1475-1479(1994).
RN   [3]
RP   ERRATUM OF PUBMED:7509073.
RA   Rogowski R.S., Krueger B.K., Collins J.H., Blaustein M.P.;
RL   Proc. Natl. Acad. Sci. U.S.A. 93:12051-12051(1996).
RN   [4]
RP   PROTEIN SEQUENCE OF 23-52, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RA   Possani L.D., Martin B.M., Svendsen I.;
RT   "The primary structure of noxiustoxin. A K channel blocking peptide,
RT   purified from the venom of the scorpion Centruroides noxius Hoffmann.";
RL   Carlsberg Res. Commun. 47:285-289(1982).
RN   [5]
RP   PARTIAL PROTEIN SEQUENCE, FUNCTION, AND NOMENCLATURE.
RC   TISSUE=Venom;
RX   PubMed=24590385; DOI=10.3390/toxins6030892;
RA   Cerni F.A., Pucca M.B., Peigneur S., Cremonez C.M., Bordon K.C., Tytgat J.,
RA   Arantes E.C.;
RT   "Electrophysiological characterization of Ts6 and Ts7, K+ channel toxins
RT   isolated through an improved Tityus serrulatus venom purification
RT   procedure.";
RL   Toxins 6:892-913(2014).
RN   [6]
RP   FUNCTION AS KV1.3 CHANNEL BLOCKER, AND MASS SPECTROMETRY.
RX   PubMed=12871837; DOI=10.1038/sj.bjp.0705343;
RA   Rodrigues A.R., Arantes E.C., Monje F., Stuehmer W., Varanda W.A.;
RT   "Tityustoxin-K(alpha) blockade of the voltage-gated potassium channel
RT   Kv1.3.";
RL   Br. J. Pharmacol. 139:1180-1186(2003).
RN   [7]
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   [8]
RP   STRUCTURE BY NMR OF 23-59, DISULFIDE BONDS, AND MUTAGENESIS OF LYS-49.
RX   PubMed=11352729; DOI=10.1021/bi010173g;
RA   Ellis K.C., Tenenholz T.C., Jerng H., Hayhurst M., Dudlak C.S., Gilly W.F.,
RA   Blaustein M.P., Weber D.J.;
RT   "Interaction of a toxin from the scorpion Tityus serrulatus with a cloned
RT   K+ channel from squid (sqKv1A).";
RL   Biochemistry 40:5942-5953(2001).
CC   -!- FUNCTION: Potently blocks Kv1.1/KCNA1 (85%), Kv1.2/KCNA2 (91%),
CC       Kv1.3/KCNA3 (89%), Kv1.6/KCNA6 (94%), and Shaker (97%).
CC       {ECO:0000269|PubMed:12871837, ECO:0000269|PubMed:24590385,
CC       ECO:0000269|PubMed:7509073}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7509073,
CC       ECO:0000269|Ref.4}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:7509073, ECO:0000305|Ref.4}.
CC   -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to a
CC       beta-sheet by disulfide bonds (CSalpha/beta).
CC   -!- MASS SPECTROMETRY: Mass=3942; Method=Unknown;
CC       Evidence={ECO:0000269|PubMed:12871837};
CC   -!- MISCELLANEOUS: Negative results: inhibits with low efficiency
CC       Kv1.5/KCNA5, Kv2.1/KCNB1, Kv7.1/KCNQ1 and ERG/KCNH2. Does not inhibit
CC       Kv1.4/KCNA4, Kv3.1/KCNC1, Kv7.2/KCNQ2 (PubMed:24590385) and
CC       ERG1/Kv11.1/KCNH2 (PubMed:18687312). {ECO:0000269|PubMed:18687312,
CC       ECO:0000269|PubMed:24590385}.
CC   -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC       channel inhibitor family. Alpha-KTx 04 subfamily. {ECO:0000305}.
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DR   EMBL; MT450710; QPD99046.1; -; mRNA.
DR   PDB; 1HP2; NMR; -; A=23-59.
DR   PDBsum; 1HP2; -.
DR   AlphaFoldDB; P46114; -.
DR   SMR; P46114; -.
DR   EvolutionaryTrace; P46114; -.
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; Knottin, scorpion toxin-like; 1.
DR   InterPro; IPR036574; Scorpion_toxin-like_sf.
DR   InterPro; IPR001947; Scorpion_toxinS_K_inh.
DR   Pfam; PF00451; Toxin_2; 1.
DR   PRINTS; PR00286; CHARYBDTOXIN.
DR   SUPFAM; SSF57095; Scorpion toxin-like; 1.
DR   PROSITE; PS01138; SCORP_SHORT_TOXIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Neurotoxin; Potassium channel impairing toxin;
KW   Secreted; Signal; Toxin; Voltage-gated potassium channel impairing toxin.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000305|PubMed:7509073, ECO:0000305|Ref.4"
FT   PEPTIDE         23..59
FT                   /note="Potassium channel toxin alpha-KTx 4.1"
FT                   /evidence="ECO:0000269|PubMed:7509073"
FT                   /id="PRO_0000044923"
FT   REGION          48..55
FT                   /note="Interaction with Ca(2+)-activated K(+) channels"
FT                   /evidence="ECO:0000255"
FT   SITE            49
FT                   /note="Basic residue of the functional dyad"
FT                   /evidence="ECO:0000250|UniProtKB:O46028"
FT   SITE            58
FT                   /note="Aromatic residue of the functional dyad"
FT                   /evidence="ECO:0000250|UniProtKB:O46028"
FT   DISULFID        29..50
FT                   /evidence="ECO:0000269|PubMed:11352729,
FT                   ECO:0000312|PDB:1HP2"
FT   DISULFID        35..55
FT                   /evidence="ECO:0000269|PubMed:11352729,
FT                   ECO:0000312|PDB:1HP2"
FT   DISULFID        39..57
FT                   /evidence="ECO:0000269|PubMed:11352729,
FT                   ECO:0000312|PDB:1HP2"
FT   MUTAGEN         49
FT                   /note="K->A,E,R: Significant loss of affinity for squid
FT                   Kv1A channel."
FT                   /evidence="ECO:0000269|PubMed:11352729"
FT   HELIX           32..42
FT                   /evidence="ECO:0007829|PDB:1HP2"
FT   STRAND          48..51
FT                   /evidence="ECO:0007829|PDB:1HP2"
FT   STRAND          54..57
FT                   /evidence="ECO:0007829|PDB:1HP2"
SQ   SEQUENCE   59 AA;  6488 MW;  BDF7F7BEC1D06F35 CRC64;
     MKAFYGILII FILISMIDLS KQVFINAKCR GSPECLPKCK EAIGKAAGKC MNGKCKCYP
//