KAX41_TITSE
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 03-AUG-2022, entry version 100.
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: Inhibits with low efficiency Kv1.5/KCNA5, Kv2.1/KCNB1,
CC Kv7.1/KCNQ1 and ERG/KCNH2. Does not inhibit Kv1.4/KCNA4, Kv3.1/KCNC1,
CC Kv7.2/KCNQ2 (PubMed:24590385) and ERG1/Kv11.1/KCNH2 (PubMed:18687312).
CC {ECO:0000269|PubMed:18687312, 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; -; 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; SSF57095; 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
