KAX82_MESMA
ID KAX82_MESMA Reviewed; 57 AA.
AC Q9U8D2; Q9U522;
DT 19-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 85.
DE RecName: Full=Potassium channel toxin alpha-KTx 8.2 {ECO:0000305};
DE AltName: Full=Neurotoxin BmP01 {ECO:0000303|PubMed:10386622, ECO:0000303|PubMed:9151979};
DE Flags: Precursor;
OS Mesobuthus martensii (Manchurian scorpion) (Buthus martensii).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus.
OX NCBI_TaxID=34649;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Venom gland;
RX PubMed=10386622; DOI=10.1016/s0014-5793(99)00651-1;
RA Wu J.-J., Dai L., Lan Z.-D., Chi C.-W.;
RT "Genomic organization of three neurotoxins active on small conductance
RT Ca2+-activated potassium channels from the scorpion Buthus martensi
RT Karsch.";
RL FEBS Lett. 452:360-364(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RA Zhu S.-Y., Zeng X.-C., Li W.-X., Jiang D.-H.;
RT "Molecular characterization of a K+ channel blocker from Buthus
RT martensii.";
RL Kexue Tongbao 44:2295-2299(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 29-46, FUNCTION, BIOASSAY,
RP AND MASS SPECTROMETRY.
RC TISSUE=Venom, and Venom gland;
RX PubMed=26389953; DOI=10.3390/toxins7093671;
RA Hakim M.A., Jiang W., Luo L., Li B., Yang S., Song Y., Lai R.;
RT "Scorpion toxin, BmP01, induces pain by targeting TRPV1 channel.";
RL Toxins 7:3671-3687(2015).
RN [4]
RP PROTEIN SEQUENCE OF 29-57, MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND
RP BIOASSAY.
RC TISSUE=Venom;
RX PubMed=9151979; DOI=10.1111/j.1432-1033.1997.00457.x;
RA Romi-Lebrun R., Martin-Eauclaire M.-F., Escoubas P., Wu F.Q., Lebrun B.,
RA Hisada M., Nakajima T.;
RT "Characterization of four toxins from Buthus martensi scorpion venom, which
RT act on apamin-sensitive Ca2+-activated K+ channels.";
RL Eur. J. Biochem. 245:457-464(1997).
RN [5]
RP PROTEIN SEQUENCE OF 29-38, STRUCTURE BY NMR OF 29-57, DISULFIDE BONDS, AND
RP MASS SPECTROMETRY.
RX PubMed=11027603; DOI=10.1006/bbrc.2000.3435;
RA Wu G., Li Y., Wei D., He F., Jiang S., Hu G., Wu H.;
RT "Solution structure of BmP01 from the venom of scorpion Buthus martensii
RT Karsch.";
RL Biochem. Biophys. Res. Commun. 276:1148-1154(2000).
RN [6]
RP PROTEIN SEQUENCE OF 29-38, MASS SPECTROMETRY, AND FUNCTION.
RC TISSUE=Venom;
RX PubMed=20889474; DOI=10.1074/mcp.m110.002832;
RA Zhu S., Peigneur S., Gao B., Luo L., Jin D., Zhao Y., Tytgat J.;
RT "Molecular diversity and functional evolution of scorpion potassium channel
RT toxins.";
RL Mol. Cell. Proteomics 10:M110.002832-M110.002832(2011).
RN [7]
RP FUNCTION.
RC TISSUE=Venom gland;
RX PubMed=22511981; DOI=10.1371/journal.pone.0035154;
RA Chen Z.Y., Zeng D.Y., Hu Y.T., He Y.W., Pan N., Ding J.P., Cao Z.J.,
RA Liu M.L., Li W.X., Yi H., Jiang L., Wu Y.L.;
RT "Structural and functional diversity of acidic scorpion potassium channel
RT toxins.";
RL PLoS ONE 7:E35154-E35154(2012).
CC -!- FUNCTION: This toxin inhibits rKv1.1/KCNA1 (100% inhibition at 3 uM),
CC Kv1.3/KCNA3 (human, mouse and rat) (IC(50)=269-467 nM), shaker IR (60%
CC at 3 uM) and activates the mouse capsaicin receptor TRPV1 (EC(50)=132
CC uM, at 20 degrees Celsius), a non-selective cation channel expressed by
CC sensory neurons of the pain pathway (PubMed:26389953, PubMed:20889474).
CC In vivo, intraplantar injection of this toxin in WT mice hind paw shows
CC significant acute pain, whereas no pain is observed when the toxin is
CC injected into TRPV1 KO mice (PubMed:26389953). In addition,
CC subcutaneous injection into mice (185 mg) produces an excitation of the
CC animal, but no lethality, whereas injection into cockroaches does not
CC provoke lethality as well (PubMed:9151979).
CC {ECO:0000269|PubMed:20889474, ECO:0000269|PubMed:22511981,
CC ECO:0000269|PubMed:26389953}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9151979}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:9151979}.
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:11027603}.
CC -!- MASS SPECTROMETRY: Mass=3178.6; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:26389953};
CC -!- MASS SPECTROMETRY: Mass=3177.47; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:9151979};
CC -!- MASS SPECTROMETRY: Mass=3177; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11027603};
CC -!- MASS SPECTROMETRY: Mass=3177.04; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:20889474};
CC -!- MISCELLANEOUS: Does not block mKv1.1/KCNA1 (PubMed:26389953). Does not
CC inhibit rKv1.2/KCNA2, rKv1.4/KCNA4, rKv1.5/KCNA5, rKv1.6/KCNA6,
CC rKv11.1/KCNH2/ERG1 (PubMed:20889474). Shows a very weak inhibition of
CC Kv7.1/KCNQ1 channels (4% at 10 uM) (PubMed:22511981).
CC {ECO:0000305|PubMed:22511981}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 08 subfamily. {ECO:0000305}.
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DR EMBL; AF095781; AAF03045.1; -; Genomic_DNA.
DR EMBL; AF114024; AAF24057.1; -; mRNA.
DR PDB; 1WM7; NMR; -; A=29-57.
DR PDBsum; 1WM7; -.
DR AlphaFoldDB; Q9U8D2; -.
DR SMR; Q9U8D2; -.
DR EvolutionaryTrace; Q9U8D2; -.
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; IPR008911; Toxin_alpha-KTx_8/9.
DR Pfam; PF05453; Toxin_6; 1.
DR SUPFAM; SSF57095; SSF57095; 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..28
FT /evidence="ECO:0000269|PubMed:11027603,
FT ECO:0000269|PubMed:26389953, ECO:0000269|PubMed:9151979"
FT PEPTIDE 29..57
FT /note="Potassium channel toxin alpha-KTx 8.2"
FT /evidence="ECO:0000269|PubMed:9151979"
FT /id="PRO_0000035348"
FT DISULFID 31..47
FT /evidence="ECO:0000269|PubMed:11027603,
FT ECO:0000312|PDB:1WM7"
FT DISULFID 34..52
FT /evidence="ECO:0000269|PubMed:11027603,
FT ECO:0000312|PDB:1WM7"
FT DISULFID 38..54
FT /evidence="ECO:0000269|PubMed:11027603,
FT ECO:0000312|PDB:1WM7"
FT CONFLICT 17
FT /note="V -> I (in Ref. 2; AAF24057)"
FT /evidence="ECO:0000305"
FT CONFLICT 21
FT /note="T -> I (in Ref. 2; AAF24057)"
FT /evidence="ECO:0000305"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:1WM7"
FT TURN 35..42
FT /evidence="ECO:0007829|PDB:1WM7"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:1WM7"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:1WM7"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:1WM7"
SQ SEQUENCE 57 AA; 6318 MW; 4265970F1250B53A CRC64;
MSRLYAIILI ALVFNVVMTI TPDMKVEAAT CEDCPEHCAT QNARAKCDND KCVCEPK
