ID   KAX22_CENMA             Reviewed;          39 AA.
AC   P40755;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   25-MAY-2022, entry version 100.
DE   RecName: Full=Potassium channel toxin alpha-KTx 2.2;
DE   AltName: Full=Margatoxin {ECO:0000303|PubMed:8360176};
DE            Short=MgTX {ECO:0000303|PubMed:8360176};
OS   Centruroides margaritatus (Central American bark Scorpion).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Centruroides.
OX   NCBI_TaxID=29018;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=8360176; DOI=10.1016/s0021-9258(17)46707-x;
RA   Garcia-Calvo M., Leonard R.J., Novick J., Stevens S.P., Schmalhofer W.,
RA   Kaczorowski G.J., Garcia M.L.;
RT   "Purification, characterization, and biosynthesis of margatoxin, a
RT   component of Centruroides margaritatus venom that selectively inhibits
RT   voltage-dependent potassium channels.";
RL   J. Biol. Chem. 268:18866-18874(1993).
RN   [2]
RP   SYNTHESIS, AND DISULFIDE BONDS.
RX   PubMed=8297371; DOI=10.1006/bbrc.1994.1090;
RA   Bednarek M.A., Bugianesi R.M., Leonard R.J., Felix J.P.;
RT   "Chemical synthesis and structure-function studies of margatoxin, a potent
RT   inhibitor of voltage-dependent potassium channel in human T lymphocytes.";
RL   Biochem. Biophys. Res. Commun. 198:619-625(1994).
RN   [3]
RP   FUNCTION, AND ACTIVITY PROFILE.
RX   PubMed=9446567; DOI=10.1074/jbc.273.5.2639;
RA   Koschak A., Bugianesi R.M., Mitterdorfer J., Kaczorowski G.J., Garcia M.L.,
RA   Knaus H.-G.;
RT   "Subunit composition of brain voltage-gated potassium channels determined
RT   by hongotoxin-1, a novel peptide derived from Centruroides limbatus
RT   venom.";
RL   J. Biol. Chem. 273:2639-2644(1998).
RN   [4]
RP   STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX   PubMed=7999764; DOI=10.1021/bi00254a015;
RA   Johnson B.A., Stevens S.P., Williamson J.M.;
RT   "Determination of the three-dimensional structure of margatoxin by 1H, 13C,
RT   15N triple-resonance nuclear magnetic resonance spectroscopy.";
RL   Biochemistry 33:15061-15070(1994).
CC   -!- FUNCTION: Potent inhibitor of voltage-gated potassium channels such as
CC       Kv1.1/KCNA1 (IC(50)=0.144 nM), Kv1.2/KCNA2 (IC(50)=0.675 nM),
CC       Kv1.3/KCNA3 (IC(50)=0.23 nM) and Shaker (Kd=160 nM).
CC       {ECO:0000269|PubMed:8360176}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8360176}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:8360176}.
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:7999764}.
CC   -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC       channel inhibitor family. Alpha-KTx 02 subfamily. {ECO:0000305}.
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DR   PIR; A48523; A48523.
DR   PDB; 1MTX; NMR; -; A=1-39.
DR   PDBsum; 1MTX; -.
DR   AlphaFoldDB; P40755; -.
DR   BMRB; P40755; -.
DR   SMR; P40755; -.
DR   TCDB; 8.B.8.1.3; the Alpha-ktx15 scorpion toxin (Alpha-ktx15) family.
DR   EvolutionaryTrace; P40755; -.
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; Toxin; Voltage-gated potassium channel impairing toxin.
FT   PEPTIDE         1..39
FT                   /note="Potassium channel toxin alpha-KTx 2.2"
FT                   /evidence="ECO:0000269|PubMed:8360176"
FT                   /id="PRO_0000044904"
FT   REGION          37..39
FT                   /note="Interaction with Kv1.3 channels"
FT                   /evidence="ECO:0000255"
FT   SITE            28
FT                   /note="Basic residue of the functional dyad"
FT                   /evidence="ECO:0000250"
FT   SITE            37
FT                   /note="Aromatic residue of the functional dyad"
FT                   /evidence="ECO:0000250"
FT   DISULFID        7..29
FT                   /evidence="ECO:0000269|PubMed:7999764"
FT   DISULFID        13..34
FT                   /evidence="ECO:0000269|PubMed:7999764"
FT   DISULFID        17..36
FT                   /evidence="ECO:0000269|PubMed:7999764"
FT   HELIX           10..13
FT                   /evidence="ECO:0007829|PDB:1MTX"
FT   HELIX           14..20
FT                   /evidence="ECO:0007829|PDB:1MTX"
FT   STRAND          26..30
FT                   /evidence="ECO:0007829|PDB:1MTX"
FT   STRAND          33..37
FT                   /evidence="ECO:0007829|PDB:1MTX"
SQ   SEQUENCE   39 AA;  4185 MW;  0FB748318014BE0D CRC64;
     TIINVKCTSP KQCLPPCKAQ FGQSAGAKCM NGKCKCYPH