KAX54_HOTTA
ID KAX54_HOTTA Reviewed; 31 AA.
AC P59869;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2003, sequence version 1.
DT 25-MAY-2022, entry version 76.
DE RecName: Full=Potassium channel toxin alpha-KTx 5.4 {ECO:0000303|PubMed:24821061};
DE AltName: Full=Tamapin {ECO:0000303|PubMed:12239213};
OS Hottentotta tamulus (Eastern Indian scorpion) (Mesobuthus tamulus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus.
OX NCBI_TaxID=34647;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, AMIDATION AT TYR-31, MASS SPECTROMETRY, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=12239213; DOI=10.1074/jbc.m206465200;
RA Pedarzani P., D'hoedt D., Doorty K.B., Wadsworth J.D.F., Joseph J.S.,
RA Jeyaseelan K., Kini R.M., Gadre S.V., Sapatnekar S.M., Stocker M.,
RA Strong P.N.;
RT "Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus)
RT that targets small conductance Ca2+-activated K+ channels and
RT afterhyperpolarization currents in central neurons.";
RL J. Biol. Chem. 277:46101-46109(2002).
RN [2]
RP STRUCTURE BY NMR, DISULFIDE BOND, AND MUTAGENESIS OF ALA-1; ARG-6; ARG-7
RP AND ARG-13.
RX PubMed=24821061; DOI=10.1021/tx4004193;
RA Ramirez-Cordero B., Toledano Y., Cano-Sanchez P., Hernandez-Lopez R.,
RA Flores-Solis D., Saucedo-Yanez A.L., Chavez-Uribe I., Brieba L.G.,
RA del Rio-Portilla F.;
RT "Cytotoxicity of recombinant tamapin and related toxin-like peptides on
RT model cell lines.";
RL Chem. Res. Toxicol. 27:960-967(2014).
CC -!- FUNCTION: Blocks small conductance calcium-activated potassium channels
CC (PubMed:12239213). Shows activity on KCa2.2/KCNN2 (IC(50)=0.0243 nM),
CC KCa2.3/KCNN3 (IC(50)=1.7 nM), and KCa2.1/KCNN1 (IC(50)=42 nM)
CC (PubMed:12239213). Induces cell death when tested on Jurkat E6-1 and
CC human mammary breast cancer MDA-MB-231 which constituvely express
CC KCa2.2/KCNN2, but not on human peripheral blood lymphocytes (which do
CC not express KCa2.2/KCNN2) (PubMed:24821061).
CC {ECO:0000269|PubMed:12239213}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12239213}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:12239213}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to a
CC beta-sheet by disulfide bonds (CSalpha/beta).
CC {ECO:0000269|PubMed:24821061}.
CC -!- MASS SPECTROMETRY: Mass=3457.9; Mass_error=0.2; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:12239213};
CC -!- MISCELLANEOUS: Does not show inhibition on KCa3.1/KCNN4 at
CC concentrations up to 50 nM. {ECO:0000269|PubMed:12239213}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 05 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR PDB; 2KY3; NMR; -; A=1-31.
DR PDB; 2LU9; NMR; -; A=1-31.
DR PDB; 2ME7; NMR; -; A=1-31.
DR PDB; 2MEL; NMR; -; A=1-31.
DR PDB; 2MEN; NMR; -; A=1-31.
DR PDB; 2MEO; NMR; -; A=1-31.
DR PDB; 6D3T; NMR; -; A=1-29.
DR PDB; 6D8H; NMR; -; A=1-31.
DR PDB; 6D8Q; NMR; -; A=1-31.
DR PDB; 6D8R; NMR; -; A=1-31.
DR PDB; 6D8S; NMR; -; A=1-31.
DR PDB; 6D8T; NMR; -; A=1-31.
DR PDB; 6D8U; NMR; -; A=1-31.
DR PDB; 6D8Y; NMR; -; A=1-30.
DR PDB; 6D93; NMR; -; A=1-30.
DR PDB; 6D9O; NMR; -; A=1-31.
DR PDB; 6D9P; NMR; -; A=1-31.
DR PDB; 6VNZ; NMR; -; A=1-31.
DR PDBsum; 2KY3; -.
DR PDBsum; 2LU9; -.
DR PDBsum; 2ME7; -.
DR PDBsum; 2MEL; -.
DR PDBsum; 2MEN; -.
DR PDBsum; 2MEO; -.
DR PDBsum; 6D3T; -.
DR PDBsum; 6D8H; -.
DR PDBsum; 6D8Q; -.
DR PDBsum; 6D8R; -.
DR PDBsum; 6D8S; -.
DR PDBsum; 6D8T; -.
DR PDBsum; 6D8U; -.
DR PDBsum; 6D8Y; -.
DR PDBsum; 6D93; -.
DR PDBsum; 6D9O; -.
DR PDBsum; 6D9P; -.
DR PDBsum; 6VNZ; -.
DR AlphaFoldDB; P59869; -.
DR BMRB; P59869; -.
DR SMR; P59869; -.
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 InterPro; IPR036574; Scorpion_toxin-like_sf.
DR InterPro; IPR001947; Scorpion_toxinS_K_inh.
DR Pfam; PF00451; Toxin_2; 1.
DR SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS01138; SCORP_SHORT_TOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation;
KW Calcium-activated potassium channel impairing toxin;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Potassium channel impairing toxin; Secreted; Toxin.
FT PEPTIDE 1..31
FT /note="Potassium channel toxin alpha-KTx 5.4"
FT /evidence="ECO:0000269|PubMed:12239213"
FT /id="PRO_0000044930"
FT REGION 6..9
FT /note="[R/K]XCQ motif"
FT /evidence="ECO:0000305|PubMed:24821061"
FT MOD_RES 31
FT /note="Tyrosine amide"
FT /evidence="ECO:0000305|PubMed:12239213"
FT DISULFID 3..21
FT /evidence="ECO:0000269|PubMed:24821061,
FT ECO:0000312|PDB:2LU9"
FT DISULFID 8..26
FT /evidence="ECO:0000269|PubMed:24821061,
FT ECO:0000312|PDB:2LU9"
FT DISULFID 12..28
FT /evidence="ECO:0000269|PubMed:24821061,
FT ECO:0000312|PDB:2LU9"
FT MUTAGEN 1
FT /note="A->GSA: 1.14-fold decrease in cell death of Jurkat
FT cells. In GS-R7A; 2.01-fold decrease in cell death of
FT Jurkat cells."
FT /evidence="ECO:0000269|PubMed:24821061"
FT MUTAGEN 6
FT /note="R->A: 1.34-fold decrease in cell death of Jurkat
FT cells. In r-R6A-R7A; 1.74-fold decrease in cell death of
FT Jurkat cells."
FT /evidence="ECO:0000269|PubMed:24821061"
FT MUTAGEN 7
FT /note="R->A: In r-R6A-R7A; 1.74-fold decrease in cell death
FT of Jurkat cells. In GS-R7A; 2.01-fold decrease in cell
FT death of Jurkat cells."
FT /evidence="ECO:0000269|PubMed:24821061"
FT MUTAGEN 13
FT /note="R->A: 1.45-fold decrease in cell death of Jurkat
FT cells."
FT /evidence="ECO:0000269|PubMed:24821061"
FT HELIX 5..12
FT /evidence="ECO:0007829|PDB:2KY3"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:2KY3"
FT STRAND 17..20
FT /evidence="ECO:0007829|PDB:2KY3"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:2KY3"
SQ SEQUENCE 31 AA; 3465 MW; FE643CDC54CA415C CRC64;
AFCNLRRCEL SCRSLGLLGK CIGEECKCVP Y
