KA121_TITSE
ID KA121_TITSE Reviewed; 62 AA.
AC P59936; A0A218QXB7;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-AUG-2022, sequence version 3.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Potassium channel toxin alpha-KTx 12.1 {ECO:0000303|PubMed:15772309};
DE AltName: Full=Butantoxin {ECO:0000303|PubMed:10864437};
DE Short=BuTX {ECO:0000303|PubMed:10864437};
DE AltName: Full=Tityustoxin-6 {ECO:0000305};
DE Short=Ts6 {ECO:0000303|PubMed:21549737, ECO:0000303|PubMed:23085190, ECO:0000303|PubMed:24590385, ECO:0000303|Ref.2};
DE AltName: Full=TsTX-IV {ECO:0000303|PubMed:10082164};
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:JAW06993.1, ECO:0000312|EMBL:JAW07035.1}
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:QCZ41150.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Sales-Medina D.F., Leal H.G., Biscoto G.L., Horta C.C.R., Carmo A.O.,
RA Kalapothakis E., de Oliveira-Mendes B.B.R.;
RT "Recombinant Ts6 toxin from Tityus serrulatus: Cloning, expression and
RT evaluation of its immunogenic potential.";
RL Submitted (NOV-2018) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:QPD99045.1}
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 [4]
RP PROTEIN SEQUENCE OF 23-62, FUNCTION, SUBCELLULAR LOCATION, TOXIC DOSE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=10082164; DOI=10.1016/s0041-0101(98)00206-2;
RA Novello J.C., Arantes E.C., Varanda W.A., Oliveira B., Giglio J.R.,
RA Marangoni S.;
RT "TsTX-IV, a short chain four-disulfide-bridged neurotoxin from Tityus
RT serrulatus venom which acts on Ca2+-activated K+ channels.";
RL Toxicon 37:651-660(1999).
RN [5]
RP PROTEIN SEQUENCE OF 23-62, SUBCELLULAR LOCATION, STRUCTURE BY NMR OF 23-62,
RP DISULFIDE BONDS, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=10864437; DOI=10.1006/abbi.2000.1858;
RA Holaday S.K. Jr., Martin B.M., Fletcher P.L. Jr., Krishna N.R.;
RT "NMR solution structure of butantoxin.";
RL Arch. Biochem. Biophys. 379:18-27(2000).
RN [6]
RP PROTEIN SEQUENCE OF 23-62, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND
RP DISULFIDE BONDS.
RX PubMed=12630699; DOI=10.1002/psc.440;
RA Pimenta A.M.C., Mansuelle P., Diniz C.R., Martin-Eauclaire M.-F.;
RT "Covalent structure and some pharmacological features of native and cleaved
RT alpha-KTx12-1, a four disulfide-bridged toxin from Tityus serrulatus
RT venom.";
RL J. Pept. Sci. 9:132-140(2003).
RN [7]
RP PROTEIN SEQUENCE OF 23-32, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom {ECO:0000303|PubMed:25199494};
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).
RN [8]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
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 [9]
RP FUNCTION.
RX PubMed=21549737; DOI=10.1016/j.toxicon.2011.04.017;
RA Zoccal K.F., Bitencourt C.S., Secatto A., Sorgi C.A., Bordon K.C.,
RA Sampaio S.V., Arantes E.C., Faccioli L.H.;
RT "Tityus serrulatus venom and toxins Ts1, Ts2 and Ts6 induce macrophage
RT activation and production of immune mediators.";
RL Toxicon 57:1101-1108(2011).
RN [10]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=23085190; DOI=10.1016/j.toxicon.2012.10.002;
RA Zoccal K.F., Bitencourt C.S., Sorgi C.A., Bordon K.C., Sampaio S.V.,
RA Arantes E.C., Faccioli L.H.;
RT "Ts6 and Ts2 from Tityus serrulatus venom induce inflammation by mechanisms
RT dependent on lipid mediators and cytokine production.";
RL Toxicon 61:1-10(2013).
RN [11]
RP STRUCTURE BY NMR OF 23-62, MASS SPECTROMETRY, AND DISULFIDE BONDS.
RX PubMed=15772309; DOI=10.1110/ps.041131205;
RA Oyama S. Jr., Pristovsek P., Franzoni L., Pertinhez T.A., Schinina E.,
RA Luecke C., Rueterjans H., Arantes E.C., Spisni A.;
RT "Probing the pH-dependent structural features of alpha-KTx12.1, a potassium
RT channel blocker from the scorpion Tityus serrulatus.";
RL Protein Sci. 14:1025-1038(2005).
RN [12]
RP STRUCTURE BY NMR OF MAUROTOXIN-BUTANTOXIN CHIMERA.
RX PubMed=15971207; DOI=10.1002/prot.20509;
RA M'Barek S., Chagot B., Andreotti N., Visan V., Mansuelle P., Grissmer S.,
RA Marrakchi M., El Ayeb M., Sampieri F., Darbon H., Fajloun Z., De Waard M.,
RA Sabatier J.-M.;
RT "Increasing the molecular contacts between maurotoxin and Kv1.2 channel
RT augments ligand affinity.";
RL Proteins 60:401-411(2005).
CC -!- FUNCTION: Potently blocks Kv1.3/KCNA3, Kv1.2/KCNA2, and Shaker
CC potassium channels (PubMed:24590385) and inhibits high conductance
CC calcium-activated potassium channels (PubMed:10082164). Is potent
CC against Kv1.3/KCNN3 (IC(50)=0.55 nM) and Kv1.2/KCNN2 (IC(50)=6.19 nM)
CC (PubMed:24590385). It also stimulates the release of NO, IL-6 and TNF-
CC alpha in J774.1 cells and presents a pro-inflammatory activity in mice
CC (PubMed:21549737, PubMed:23085190). {ECO:0000269|PubMed:10082164,
CC ECO:0000269|PubMed:21549737, ECO:0000269|PubMed:23085190,
CC ECO:0000269|PubMed:24590385}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10082164,
CC ECO:0000269|PubMed:10864437, ECO:0000269|PubMed:12630699,
CC ECO:0000269|PubMed:24590385, 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 a
CC beta-sheet by disulfide bonds (CSalpha/beta). {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=4508.08; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:12630699};
CC -!- MASS SPECTROMETRY: Mass=4505.8; Mass_error=0.5; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:15772309};
CC -!- TOXIC DOSE: LD(50) is 826 ug/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:10082164}.
CC -!- MISCELLANEOUS: The N-terminal C2-C5 disulfide bridge unique to this
CC toxin does not appear to confer stability to the protein.
CC -!- MISCELLANEOUS: Inhibits with a low efficiency Kv1.1/KCNA1, Kv1.5/KCNA5,
CC Kv1.6/KCNA6, Kv4.3/KCND3, Kv7.1/KCNQ1, Kv7.2/KCNQ2, Kv7.4/KCNQ4, and
CC ERG/KCNH2, and does not inhibit Kv1.4/KCNA4, Kv2.1/KCNB1, and
CC Kv3.1/KCNC1. {ECO:0000305|PubMed:24590385}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 12 subfamily. {ECO:0000305}.
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DR EMBL; GEUW01000052; JAW06993.1; -; mRNA.
DR EMBL; GEUW01000010; JAW07035.1; -; mRNA.
DR EMBL; MK159306; QCZ41150.1; -; mRNA.
DR EMBL; MT450709; QPD99045.1; -; mRNA.
DR PDB; 1C55; NMR; -; A=23-62.
DR PDB; 1C56; NMR; -; A=23-62.
DR PDB; 1WT7; NMR; -; A=23-31.
DR PDBsum; 1C55; -.
DR PDBsum; 1C56; -.
DR PDBsum; 1WT7; -.
DR AlphaFoldDB; P59936; -.
DR BMRB; P59936; -.
DR SMR; P59936; -.
DR EvolutionaryTrace; P59936; -.
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; Calcium-activated potassium channel impairing toxin;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Potassium channel impairing toxin; Secreted; Signal; Toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..62
FT /note="Potassium channel toxin alpha-KTx 12.1"
FT /evidence="ECO:0000269|PubMed:10082164,
FT ECO:0000269|PubMed:10864437, ECO:0000269|PubMed:12630699"
FT /id="PRO_0000066838"
FT SITE 52
FT /note="Basic residue of the functional dyad"
FT /evidence="ECO:0000250"
FT SITE 61
FT /note="Aromatic residue of the functional dyad"
FT /evidence="ECO:0000250"
FT DISULFID 24..27
FT /evidence="ECO:0000269|PubMed:10864437,
FT ECO:0000269|PubMed:12630699, ECO:0000269|PubMed:15772309,
FT ECO:0007744|PDB:1C55, ECO:0007744|PDB:1C56,
FT ECO:0007744|PDB:1WT7"
FT DISULFID 32..53
FT /evidence="ECO:0000269|PubMed:10864437,
FT ECO:0000269|PubMed:12630699, ECO:0000269|PubMed:15772309,
FT ECO:0007744|PDB:1C55, ECO:0007744|PDB:1C56,
FT ECO:0007744|PDB:1WT7"
FT DISULFID 38..58
FT /evidence="ECO:0000269|PubMed:10864437,
FT ECO:0000269|PubMed:12630699, ECO:0000269|PubMed:15772309,
FT ECO:0007744|PDB:1C55, ECO:0007744|PDB:1C56,
FT ECO:0007744|PDB:1WT7"
FT DISULFID 42..60
FT /evidence="ECO:0000269|PubMed:10864437,
FT ECO:0000269|PubMed:12630699, ECO:0000269|PubMed:15772309,
FT ECO:0007744|PDB:1C55, ECO:0007744|PDB:1C56,
FT ECO:0007744|PDB:1WT7"
FT CONFLICT 62
FT /note="T -> TN (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 25..31
FT /evidence="ECO:0007829|PDB:1C55"
FT HELIX 35..45
FT /evidence="ECO:0007829|PDB:1C55"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:1C55"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:1C55"
SQ SEQUENCE 62 AA; 7083 MW; 73A73207EE885334 CRC64;
MQVFYGLLLM FILCSTIHLS EQWCSTCLDL ACGASRECYD PCFKAFGRAH GKCMNNKCRC
YT
