BDS1_ANTEL
ID BDS1_ANTEL Reviewed; 42 AA.
AC P61541;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 1.
DT 25-MAY-2022, entry version 68.
DE RecName: Full=Kappa-actitoxin-Ael2a {ECO:0000303|PubMed:22683676};
DE Short=Kappa-AITX-Ael2a {ECO:0000303|PubMed:22683676};
DE AltName: Full=Toxin APETx1 {ECO:0000303|PubMed:12815161};
OS Anthopleura elegantissima (Green aggregating anemone) (Actinia
OS elegantissima).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Actiniidae; Anthopleura.
OX NCBI_TaxID=6110;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, MASS SPECTROMETRY, DISULFIDE BONDS, SUBCELLULAR
RP LOCATION, AND 3D-STRUCTURE MODELING.
RX PubMed=12815161; DOI=10.1124/mol.64.1.59;
RA Diochot S., Loret E., Bruhn T., Beress L., Lazdunski M.;
RT "APETx1, a new toxin from the sea anemone Anthopleura elegantissima, blocks
RT voltage-gated human ether-a-go-go-related gene potassium channels.";
RL Mol. Pharmacol. 64:59-69(2003).
RN [2]
RP FUNCTION.
RX PubMed=16497878; DOI=10.1124/mol.105.019729;
RA Restano-Cassulini R., Korolkova Y.V., Diochot S., Gurrola G., Guasti L.,
RA Possani L.D., Lazdunski M., Grishin E.V., Arcangeli A., Wanke E.;
RT "Species diversity and peptide toxins blocking selectivity of ether-a-go-
RT go-related gene subfamily K+ channels in the central nervous system.";
RL Mol. Pharmacol. 69:1673-1683(2006).
RN [3]
RP FUNCTION.
RX PubMed=17473056; DOI=10.1124/mol.107.035840;
RA Zhang M., Liu X.S., Diochot S., Lazdunski M., Tseng G.N.;
RT "APETx1 from sea anemone Anthopleura elegantissima is a gating modifier
RT peptide toxin of the human ether-a-go-go- related potassium channel.";
RL Mol. Pharmacol. 72:259-268(2007).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22972919; DOI=10.1096/fj.12-218479;
RA Peigneur S., Beress L., Moeller C., Mari F., Forssmann W.G., Tytgat J.;
RT "A natural point mutation changes both target selectivity and mechanism of
RT action of sea anemone toxins.";
RL FASEB J. 26:5141-5151(2012).
RN [5]
RP NOMENCLATURE.
RX PubMed=22683676; DOI=10.1016/j.toxicon.2012.05.020;
RA Oliveira J.S., Fuentes-Silva D., King G.F.;
RT "Development of a rational nomenclature for naming peptide and protein
RT toxins from sea anemones.";
RL Toxicon 60:539-550(2012).
RN [6]
RP FUNCTION AS ANTIBIOTIC.
RX PubMed=28796463; DOI=10.1111/febs.14194;
RA Kim C.H., Lee Y.J., Go H.J., Oh H.Y., Lee T.K., Park J.B., Park N.G.;
RT "Defensin-neurotoxin dyad in a basally branching metazoan sea anemone.";
RL FEBS J. 284:3320-3338(2017).
RN [7]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=15726634; DOI=10.1002/prot.20425;
RA Chagot B., Diochot S., Pimentel C., Lazdunski M., Darbon H.;
RT "Solution structure of APETx1 from the sea anemone Anthopleura
RT elegantissima: a new fold for an HERG toxin.";
RL Proteins 59:380-386(2005).
CC -!- FUNCTION: Peptide with both antimicrobial and neurotoxin activities.
CC This toxin acts both on ERG potassium channels and sodium channels
CC (PubMed:12815161,PubMed:16497878, PubMed:17473056, PubMed:22972919). It
CC potently and reversibly inhibits human Kv11.1/KCNH2/ERG1 (IC(50)=34 nM)
CC (PubMed:12815161, PubMed:16497878, PubMed:17473056), rat
CC Kv11.1/KCNH2/ERG1 (PubMed:16497878) and Kv11.3/KCNH7/ERG3
CC (PubMed:17473056) voltage-gated potassium channels in a similar
CC potency. It acts as a gating-modifier toxin that shifts the voltage-
CC dependence of ERG activation in the positive direction and suppresses
CC its current amplitudes elicited by strong depolarizing pulses
CC (PubMed:12815161, PubMed:17473056). On sodium channels, it blocks
CC Nav1.2/SCN2A (EC(50)=31 nM), Nav1.3/SCN3A, Nav1.4/SCN4A, Nav1.5/SCN5A,
CC Nav1.6/SCN8A, Nav1.8/SCN10A (EC(50)=92 nM) (PubMed:22972919). It may
CC act by binding at site 1 or close by, only when the pore is in an open
CC configuration (PubMed:22972919). Shows antibacterial activity against
CC the Gram-negative bacterium S.typhimurium, but not on the bacteria
CC B.subtilis, S.aureus, and P.aeruginosa (PubMed:28796463). In vivo, this
CC toxin does not induce neurotoxic symptoms when injected into mice
CC (PubMed:12815161). {ECO:0000269|PubMed:12815161,
CC ECO:0000269|PubMed:16497878, ECO:0000269|PubMed:17473056,
CC ECO:0000269|PubMed:22972919}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12815161,
CC ECO:0000269|PubMed:22972919}. Nematocyst {ECO:0000305}.
CC -!- DOMAIN: Has the CSbeta/beta fold, which comprises anti-parallel beta-
CC sheets stabilized by three or four disulfide bonds.
CC {ECO:0000269|PubMed:15726634}.
CC -!- MASS SPECTROMETRY: Mass=4552.21; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:12815161};
CC -!- MISCELLANEOUS: Does not block Kv11.2/KCNH6/ERG2 (PubMed:17473056),
CC Kv1.1/KCNA1, Kv1.2/KCNA2, Kv1.3/KCNA3, Kv1.5/KCNA5, Kv1.6/KCNA6,
CC Kv2.1/KCNB1, Kv3.4/KCNC4, Kv4.2/KCND2, Kv7.1/KCNQ1, Kv7.2/KCNQ2,
CC Kv7.3/KCNQ3, Kv10.1/EAG1/KCNH1 and Kv12.3/ELK1/KCNH4 (PubMed:12815161).
CC Weakly inhibits Kv1.4 KCNA4 (27%) (PubMed:12815161). Does not inhibit
CC Nav1.7/SCN9A and insect DmNav1 and BgNav1(PubMed:22972919).
CC {ECO:0000269|PubMed:12815161, ECO:0000269|PubMed:17473056,
CC ECO:0000269|PubMed:22972919}.
CC -!- SIMILARITY: Belongs to the sea anemone type 3 (BDS) potassium channel
CC toxin family. {ECO:0000305}.
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DR PDB; 1WQK; NMR; -; A=1-42.
DR PDB; 7BWI; NMR; -; A=1-42.
DR PDBsum; 1WQK; -.
DR PDBsum; 7BWI; -.
DR AlphaFoldDB; P61541; -.
DR SMR; P61541; -.
DR TCDB; 8.B.11.1.1; the sea anemone peptide toxin (apetx) family.
DR EvolutionaryTrace; P61541; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0042151; C:nematocyst; 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:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR Gene3D; 2.20.20.10; -; 1.
DR InterPro; IPR012414; BDS_K_chnl_tox.
DR InterPro; IPR023355; Myo_ane_neurotoxin_sf.
DR Pfam; PF07936; Defensin_4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Nematocyst; Neurotoxin;
KW Potassium channel impairing toxin; Secreted; Toxin;
KW Voltage-gated potassium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..42
FT /note="Kappa-actitoxin-Ael2a"
FT /evidence="ECO:0000269|PubMed:12815161"
FT /id="PRO_0000221539"
FT DISULFID 4..37
FT /evidence="ECO:0000269|PubMed:15726634,
FT ECO:0000312|PDB:1WQK"
FT DISULFID 6..30
FT /evidence="ECO:0000269|PubMed:15726634,
FT ECO:0000312|PDB:1WQK"
FT DISULFID 20..38
FT /evidence="ECO:0000269|PubMed:15726634,
FT ECO:0000312|PDB:1WQK"
FT STRAND 3..6
FT /evidence="ECO:0007829|PDB:1WQK"
FT STRAND 9..16
FT /evidence="ECO:0007829|PDB:1WQK"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:7BWI"
FT STRAND 28..32
FT /evidence="ECO:0007829|PDB:1WQK"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:1WQK"
SQ SEQUENCE 42 AA; 4558 MW; 55069008814B3715 CRC64;
GTTCYCGKTI GIYWFGTKTC PSNRGYTGSC GYFLGICCYP VD
