BDS1_ANESU
ID BDS1_ANESU Reviewed; 43 AA.
AC P11494;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 25-MAY-2022, entry version 104.
DE RecName: Full=Delta/kappa-actitoxin-Avd4a {ECO:0000303|PubMed:22683676};
DE Short=Delta/kappa-AITX-Avd4a {ECO:0000303|PubMed:22683676};
DE AltName: Full=Antihypertensive protein BDS-1;
DE AltName: Full=Blood depressing substance I {ECO:0000303|PubMed:9506974};
DE Short=BDS-I {ECO:0000303|PubMed:9506974};
OS Anemonia sulcata (Mediterranean snakelocks sea anemone).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Actiniidae; Anemonia.
OX NCBI_TaxID=6108;
RN [1]
RP PROTEIN SEQUENCE, AND FUNCTION.
RA Beress L., Doppelfeld I.-S., Etschenberg E., Graf E., Henschen-Edman A.,
RA Zwick J.;
RT "Polypeptides, process for their preparation, and their use as hypotensive
RT active compounds.";
RL Patent number DE3324689, 17-JAN-1985.
RN [2]
RP PROTEIN SEQUENCE, AND FUNCTION.
RX PubMed=9506974; DOI=10.1074/jbc.273.12.6744;
RA Diochot S., Schweitz H., Beress L., Lazdunski M.;
RT "Sea anemone peptides with a specific blocking activity against the fast
RT inactivating potassium channel Kv3.4.";
RL J. Biol. Chem. 273:6744-6749(1998).
RN [3]
RP FUNCTION.
RX PubMed=16177043; DOI=10.1523/jneurosci.2119-05.2005;
RA Yeung S.Y., Thompson D., Wang Z., Fedida D., Robertson B.;
RT "Modulation of Kv3 subfamily potassium currents by the sea anemone toxin
RT BDS: significance for CNS and biophysical studies.";
RL J. Neurosci. 25:8735-8745(2005).
RN [4]
RP FUNCTION ON NAV1.7/SCN9A.
RX PubMed=22442564; DOI=10.1152/jn.00785.2011;
RA Liu P., Jo S., Bean B.P.;
RT "Modulation of neuronal sodium channels by the sea anemone peptide BDS-I.";
RL J. Neurophysiol. 107:3155-3167(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 STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=2566325; DOI=10.1021/bi00431a032;
RA Driscoll P.C., Clore G.M., Beress L., Gronenborn A.M.;
RT "A proton nuclear magnetic resonance study of the antihypertensive and
RT antiviral protein BDS-I from the sea anemone Anemonia sulcata: sequential
RT and stereospecific resonance assignment and secondary structure.";
RL Biochemistry 28:2178-2187(1989).
RN [7]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=2566326; DOI=10.1021/bi00431a033;
RA Driscoll P.C., Gronenborn A.M., Beress L., Clore G.M.;
RT "Determination of the three-dimensional solution structure of the
RT antihypertensive and antiviral protein BDS-I from the sea anemone Anemonia
RT sulcata: a study using nuclear magnetic resonance and hybrid distance
RT geometry-dynamical simulated annealing.";
RL Biochemistry 28:2188-2198(1989).
CC -!- FUNCTION: Acts as a gating modifier on both Kv and Nav ion channels,
CC and also acts on blood pressure. Voltage-dependently inhibits voltage-
CC gated potassium channels Kv3 (Kv3.1/KCNC1, Kv3.2/KCNC2 and Kv3.4/KCNC4)
CC and slows inactivation of the voltage-gated sodium channel Nav1.7/SCN9A
CC (PubMed:16177043, PubMed:22442564, PubMed:9506974). Inhibits all Kv3.1,
CC Kv3.2 and Kv3.4 by about 50% when tested at a voltage of +40 mV (45%,
CC 48% and 56%, respectively). May act by binding residues in voltage-
CC sensing domains S3b and S4 of Kv3 (PubMed:16177043). On sodium channel,
CC tests have been done on human Nav1.7/SCN9A (expressed in HEK293 cells)
CC (EC(50)=3 nM) and rat SCG neurons that mostly carry Nav1.7 channels
CC (EC(50)=300 nM) (PubMed:22442564). This toxin also reduces blood
CC pressure (Ref.1). {ECO:0000269|PubMed:16177043,
CC ECO:0000269|PubMed:22442564, ECO:0000269|PubMed:9506974,
CC ECO:0000269|Ref.1}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Nematocyst {ECO:0000305}.
CC -!- MISCELLANEOUS: This toxin does not have effect on Nav1.1/SCN1A and
CC Nav1.6/SCN8A sodium channels (PubMed:22442564). It has little or no
CC functional effect on cardiac muscle, as well as on skeletal muscle
CC myotubes, suggesting lack of functional interaction with Nav1.4/SCN4A
CC or Nav1.5/SCN5A (PubMed:9506974). {ECO:0000269|PubMed:22442564,
CC ECO:0000269|PubMed:9506974}.
CC -!- MISCELLANEOUS: This protein sequence is identical to BDS-1 from
CC A.viridis (AC P0DMX6). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the sea anemone type 3 (BDS) potassium channel
CC toxin family. {ECO:0000305}.
CC -!- CAUTION: Opinions are divided on whether Anemonia viridis (Forsskal,
CC 1775) and Anemonia sulcata (Pennant, 1777) are separate species.
CC {ECO:0000305}.
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DR PIR; A33041; A33041.
DR PDB; 1BDS; NMR; -; A=1-43.
DR PDB; 2BDS; NMR; -; A=1-43.
DR PDBsum; 1BDS; -.
DR PDBsum; 2BDS; -.
DR AlphaFoldDB; P11494; -.
DR BMRB; P11494; -.
DR SMR; P11494; -.
DR TCDB; 8.B.11.1.3; the sea anemone peptide toxin (apetx) family.
DR EvolutionaryTrace; P11494; -.
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:0008217; P:regulation of blood pressure; 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; Direct protein sequencing; Disulfide bond; Hypotensive agent;
KW 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..43
FT /note="Delta/kappa-actitoxin-Avd4a"
FT /evidence="ECO:0000269|PubMed:9506974, ECO:0000269|Ref.1"
FT /id="PRO_0000221541"
FT DISULFID 4..39
FT /evidence="ECO:0000269|PubMed:2566326"
FT DISULFID 6..32
FT /evidence="ECO:0000269|PubMed:2566326"
FT DISULFID 22..40
FT /evidence="ECO:0000269|PubMed:2566326"
FT VARIANT 18
FT /note="L -> F"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:2BDS"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:1BDS"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:1BDS"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:1BDS"
SQ SEQUENCE 43 AA; 4714 MW; 7C17846E88E2F1D8 CRC64;
AAPCFCSGKP GRGDLWILRG TCPGGYGYTS NCYKWPNICC YPH
