KAX32_LEIHE
ID KAX32_LEIHE Reviewed; 38 AA.
AC P46111;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 25-MAY-2022, entry version 101.
DE RecName: Full=Potassium channel toxin alpha-KTx 3.2;
DE AltName: Full=Agitoxin-2 {ECO:0000303|PubMed:8204618};
DE Short=AgTx-2 {ECO:0000303|PubMed:8204618};
DE Short=AgTx2 {ECO:0000303|PubMed:8204618};
OS Leiurus hebraeus (Deathstalker scorpion) (Leiurus quinquestriatus
OS hebraeus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Leiurus.
OX NCBI_TaxID=6884;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=8204618; DOI=10.1021/bi00188a012;
RA Garcia M.L., Garcia-Calvo M., Hidalgo P., Lee A., Mackinnon R.;
RT "Purification and characterization of three inhibitors of voltage-dependent
RT K+ channels from Leiurus quinquestriatus var. hebraeus venom.";
RL Biochemistry 33:6834-6839(1994).
RN [2]
RP FUNCTION.
RX PubMed=18042681; DOI=10.1110/ps.073122908;
RA Pimentel C., M'Barek S., Visan V., Grissmer S., Sampieri F., Sabatier J.M.,
RA Darbon H., Fajloun Z.;
RT "Chemical synthesis and 1H-NMR 3D structure determination of AgTx2-MTX
RT chimera, a new potential blocker for Kv1.2 channel, derived from MTX and
RT AgTx2 scorpion toxins.";
RL Protein Sci. 17:107-118(2008).
RN [3]
RP FUNCTION.
RX PubMed=20007782; DOI=10.1073/pnas.0910123106;
RA Takacs Z., Toups M., Kollewe A., Johnson E., Cuello L.G., Driessens G.,
RA Biancalana M., Koide A., Ponte C.G., Perozo E., Gajewski T.F.,
RA Suarez-Kurtz G., Koide S., Goldstein S.A.;
RT "A designer ligand specific for Kv1.3 channels from a scorpion neurotoxin-
RT based library.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:22211-22216(2009).
RN [4]
RP FUNCTION, AND RECOMBINANT EXPRESSION.
RX PubMed=31276191; DOI=10.1002/1873-3468.13530;
RA Kasheverov I.E., Oparin P.B., Zhmak M.N., Egorova N.S., Ivanov I.A.,
RA Gigolaev A.M., Nekrasova O.V., Serebryakova M.V., Kudryavtsev D.S.,
RA Prokopev N.A., Hoang A.N., Tsetlin V.I., Vassilevski A.A., Utkin Y.N.;
RT "Scorpion toxins interact with nicotinic acetylcholine receptors.";
RL FEBS Lett. 593:2779-2789(2019).
RN [5]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=8520473; DOI=10.1002/pro.5560040805;
RA Krezel A.M., Kasibhatla C., Hidalgo P., Mackinnon R., Wagner G.;
RT "Solution structure of the potassium channel inhibitor agitoxin 2: caliper
RT for probing channel geometry.";
RL Protein Sci. 4:1478-1489(1995).
CC -!- FUNCTION: Potent inhibitor of the Shaker potassium channels and its
CC mammalian homologs (Kv1.1/KCNA1, Kv1.3/KCNA3, Kv1.6/KCNA6) (Ki<1 nM for
CC all channels) (PubMed:8204618, PubMed:20007782). Also blocks
CC Kv1.2/KCNA2 (IC(50)=26.8 nM) (PubMed:8204618, PubMed:20007782). It also
CC shows a weak interaction with nicotinic acetylcholine receptors
CC (nAChR), suggesting it may weakly inhibit it (PubMed:31276191).
CC {ECO:0000269|PubMed:20007782, ECO:0000269|PubMed:8204618}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8204618}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8204618}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to a
CC beta-sheet by disulfide bonds (CSalpha/beta).
CC -!- MISCELLANEOUS: Shows weak blocking activity on KCa3.1/KCNN4
CC (IC(50)=1152 nM) (PubMed:18042681). Does not block Kv2.1/KCNB1 (Ki
CC >2000 nM) (PubMed:8204618). {ECO:0000269|PubMed:18042681,
CC ECO:0000269|PubMed:8204618}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 03 subfamily. {ECO:0000305}.
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DR PIR; B54471; B54471.
DR PDB; 1AGT; NMR; -; A=1-38.
DR PDBsum; 1AGT; -.
DR AlphaFoldDB; P46111; -.
DR BMRB; P46111; -.
DR SMR; P46111; -.
DR EvolutionaryTrace; P46111; -.
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..38
FT /note="Potassium channel toxin alpha-KTx 3.2"
FT /evidence="ECO:0000269|PubMed:8204618"
FT /id="PRO_0000044926"
FT DISULFID 8..28
FT /evidence="ECO:0000269|PubMed:8520473"
FT DISULFID 14..33
FT /evidence="ECO:0000269|PubMed:8520473"
FT DISULFID 18..35
FT /evidence="ECO:0000269|PubMed:8520473"
FT HELIX 11..14
FT /evidence="ECO:0007829|PDB:1AGT"
FT HELIX 15..21
FT /evidence="ECO:0007829|PDB:1AGT"
FT STRAND 23..29
FT /evidence="ECO:0007829|PDB:1AGT"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:1AGT"
SQ SEQUENCE 38 AA; 4097 MW; C8BB8513F87B51CD CRC64;
GVPINVSCTG SPQCIKPCKD AGMRFGKCMN RKCHCTPK
