NA1A_ANTXA
ID NA1A_ANTXA Reviewed; 49 AA.
AC P01530; P0C5G4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 25-MAY-2022, entry version 105.
DE RecName: Full=Delta-actitoxin-Axm1a {ECO:0000303|PubMed:22683676};
DE Short=Delta-AITX-Axm1a {ECO:0000303|PubMed:22683676};
DE AltName: Full=Anthopleurin-A {ECO:0000303|PubMed:13806};
DE Short=AP-A {ECO:0000303|PubMed:13806};
DE Short=ApA {ECO:0000305};
DE AltName: Full=PCR3-3,4 {ECO:0000303|PubMed:9604281};
DE AltName: Full=Toxin PCR7 {ECO:0000305};
OS Anthopleura xanthogrammica (Giant green sea anemone) (Actinia
OS xanthogrammica).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Actiniidae; Anthopleura.
OX NCBI_TaxID=6112;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Tentacle;
RX PubMed=9604281; DOI=10.1016/s0041-0101(97)00064-0;
RA Kelso G.J., Blumenthal K.M.;
RT "Identification and characterization of novel sodium channel toxins from
RT the sea anemone Anthopleura xanthogrammica.";
RL Toxicon 36:41-51(1998).
RN [2]
RP PROTEIN SEQUENCE, AND FUNCTION.
RX PubMed=13806; DOI=10.1021/bi00621a007;
RA Tanaka M., Haniu M., Yasunobu K.T., Norton T.R.;
RT "Amino acid sequence of the Anthopleura xanthogrammica heart stimulant,
RT anthopleurin A.";
RL Biochemistry 16:204-208(1977).
RN [3]
RP DISULFIDE BONDS.
RX PubMed=6108877;
RA Norton T.R.;
RT "Cardiotonic polypeptides from Anthopleura xanthogrammica (Brandt) and A.
RT elegantissima (Brandt).";
RL Fed. Proc. 40:21-25(1981).
RN [4]
RP SITE SER-12 AND GLN-49.
RX PubMed=8276803; DOI=10.1016/s0021-9258(17)42342-8;
RA Gallagher M.J., Blumenthal K.M.;
RT "Importance of the unique cationic residues arginine 12 and lysine 49 in
RT the activity of the cardiotonic polypeptide anthopleurin B.";
RL J. Biol. Chem. 269:254-259(1994).
RN [5]
RP FUNCTION, AND SITE SER-12 AND GLN-49.
RX PubMed=7612595; DOI=10.1021/bi00027a003;
RA Khera P.K., Benzinger G.R., Lipkind G., Drum C.L., Hanck D.A.,
RA Blumenthal K.M.;
RT "Multiple cationic residues of anthopleurin B that determine high affinity
RT and channel isoform discrimination.";
RL Biochemistry 34:8533-8541(1995).
RN [6]
RP FUNCTION ON OPEN-STATE SODIUM CHANNELS.
RX PubMed=8576699; DOI=10.1085/jgp.106.4.601;
RA Hanck D.A., Sheets M.F.;
RT "Modification of inactivation in cardiac sodium channels: ionic current
RT studies with Anthopleurin-A toxin.";
RL J. Gen. Physiol. 106:601-616(1995).
RN [7]
RP FUNCTION ON CHANNEL DOMAIN 4.
RX PubMed=9306007; DOI=10.1007/s004240050460;
RA Benzinger G.R., Drum C.L., Chen L.Q., Kallen R.G., Hanck D.A., Hanck D.;
RT "Differences in the binding sites of two site-3 sodium channel toxins.";
RL Pflugers Arch. 434:742-749(1997).
RN [8]
RP FUNCTION ON FAST INACTIVATION.
RX PubMed=21099342; DOI=10.4161/chan.5.1.14031;
RA Groome J., Lehmann-Horn F., Holzherr B.;
RT "Open- and closed-state fast inactivation in sodium channels: differential
RT effects of a site-3 anemone toxin.";
RL Channels 5:65-78(2011).
RN [9]
RP REVIEW.
RX PubMed=17092528; DOI=10.1016/j.toxicon.2006.09.017;
RA Hanck D.A., Sheets M.F.;
RT "Site-3 toxins and cardiac sodium channels.";
RL Toxicon 49:181-193(2007).
RN [10]
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 [11]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=1968006; DOI=10.1111/j.1432-1033.1990.tb15337.x;
RA Mabbut B.C., Norton R.S.;
RT "Sequential 1H-NMR assignments and secondary structure of the sea anemone
RT polypeptide anthopleurin-A.";
RL Eur. J. Biochem. 187:555-563(1990).
RN [12]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=7893675; DOI=10.1021/bi00011a036;
RA Pallaghy P.K., Scanlon M.J., Monks S.A., Norton R.S.;
RT "Three-dimensional structure in solution of the polypeptide cardiac
RT stimulant anthopleurin-A.";
RL Biochemistry 34:3782-3794(1995).
CC -!- FUNCTION: Binds specifically to voltage-gated sodium channels (Nav)
CC (site 3), thereby delaying their inactivation. This toxin retains the
CC greatest capacity to discriminate between the cardiac (Nav1.5/SCN5A)
CC and neuronal sodium channels (2.5 nM versus 120 nM, when
CC electrophysiologically tested and 14 nM versus 400 nM, when tested by
CC ion flux), whereas its paralog Anthopleurin-B has the highest affinity
CC of all anemone toxins for the mammalian sodium channel (PubMed:13806,
CC PubMed:7612595, PubMed:17092528). Its ability to differentiate between
CC cardiac and skeletal channels appears to be associated with domain 4 of
CC the channel (PubMed:9306007). This toxin does not slow or inhibit
CC closed-state inactivation of cardiac sodium channels, but selectively
CC modifies inactivation from the open-state (PubMed:8576699). It does not
CC display phospholipid-binding activities, suggesting that the domain IV
CC S3-S4 linker is located at the extracellular surface and not buried in
CC the phospholipid bilayer (By similarity).
CC {ECO:0000250|UniProtKB:P01531, ECO:0000269|PubMed:13806,
CC ECO:0000269|PubMed:17092528, ECO:0000269|PubMed:21099342,
CC ECO:0000269|PubMed:8576699, ECO:0000269|PubMed:9306007}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Nematocyst {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the sea anemone sodium channel inhibitory toxin
CC family. Type I subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia;
CC URL="https://en.wikipedia.org/wiki/Anthopleurin";
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DR PIR; A90401; NAXA.
DR PDB; 1AHL; NMR; -; A=1-49.
DR PDBsum; 1AHL; -.
DR AlphaFoldDB; P01530; -.
DR BMRB; P01530; -.
DR SMR; P01530; -.
DR TCDB; 8.B.17.1.3; the sea anemone peptide toxin class iii (shi) family.
DR EvolutionaryTrace; P01530; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0042151; C:nematocyst; IEA:UniProtKB-SubCell.
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:0009966; P:regulation of signal transduction; IEA:InterPro.
DR Gene3D; 2.20.20.10; -; 1.
DR InterPro; IPR000693; Anenome_toxin.
DR InterPro; IPR023355; Myo_ane_neurotoxin_sf.
DR PIRSF; PIRSF001905; Anenome_toxin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cardiotoxin; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Nematocyst; Neurotoxin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..49
FT /note="Delta-actitoxin-Axm1a"
FT /evidence="ECO:0000269|PubMed:13806"
FT /id="PRO_0000221515"
FT SITE 12
FT /note="Key residue for high affinity and preferential
FT inhibition of sodium cardiac channels versus neuronal
FT channels"
FT /evidence="ECO:0000269|PubMed:7612595,
FT ECO:0000269|PubMed:8276803"
FT SITE 49
FT /note="Key residue for high affinity and preferential
FT inhibition of sodium cardiac channels versus neuronal
FT channels"
FT /evidence="ECO:0000269|PubMed:7612595,
FT ECO:0000269|PubMed:8276803"
FT DISULFID 4..46
FT /evidence="ECO:0000269|PubMed:1968006,
FT ECO:0000269|PubMed:6108877, ECO:0000269|PubMed:7893675"
FT DISULFID 6..36
FT /evidence="ECO:0000269|PubMed:1968006,
FT ECO:0000269|PubMed:6108877, ECO:0000269|PubMed:7893675"
FT DISULFID 29..47
FT /evidence="ECO:0000269|PubMed:1968006,
FT ECO:0000269|PubMed:6108877, ECO:0000269|PubMed:7893675"
FT STRAND 10..12
FT /evidence="ECO:0007829|PDB:1AHL"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:1AHL"
FT STRAND 42..47
FT /evidence="ECO:0007829|PDB:1AHL"
SQ SEQUENCE 49 AA; 5138 MW; A48C07BD894F94CC CRC64;
GVSCLCDSDG PSVRGNTLSG TLWLYPSGCP SGWHNCKAHG PTIGWCCKQ
