D1A_HADVE
ID D1A_HADVE Reviewed; 42 AA.
AC P13494;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 25-MAY-2022, entry version 105.
DE RecName: Full=Delta-hexatoxin-Hv1a {ECO:0000305};
DE Short=Delta-HXTX-Hv1a {ECO:0000305};
DE AltName: Full=Delta-atracotoxin-Hv1 {ECO:0000303|PubMed:9384567, ECO:0000303|PubMed:9845331};
DE Short=Delta-ACTX-Hv1 {ECO:0000303|PubMed:9384567};
DE AltName: Full=Delta-atracotoxin-Hv1a {ECO:0000303|PubMed:11171353, ECO:0000303|PubMed:11874465};
DE Short=Delta-ACTX-Hv1a {ECO:0000303|PubMed:11171353, ECO:0000303|PubMed:11874465, ECO:0000303|PubMed:18986214};
DE AltName: Full=Delta-hexatoxin-Hv1a_2 {ECO:0000305};
DE Short=Delta-HXTX-Hv1a_2 {ECO:0000305};
DE AltName: Full=Versutoxin {ECO:0000303|PubMed:3355530, ECO:0000303|PubMed:7816562, ECO:0000303|PubMed:8281423, ECO:0000303|PubMed:9028001};
DE Short=VTX {ECO:0000303|PubMed:3355530, ECO:0000303|PubMed:7816562, ECO:0000303|PubMed:8281423, ECO:0000303|PubMed:9028001};
OS Hadronyche versuta (Blue mountains funnel-web spider) (Atrax versutus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Hexathelidae; Hadronyche.
OX NCBI_TaxID=6904;
RN [1]
RP PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=3355530; DOI=10.1042/bj2500401;
RA Brown M.R., Sheumack D.D., Tyler M.I., Howden M.E.H.;
RT "Amino acid sequence of versutoxin, a lethal neurotoxin from the venom of
RT the funnel-web spider Atrax versutus.";
RL Biochem. J. 250:401-405(1988).
RN [2]
RP FUNCTION.
RX PubMed=8281423; DOI=10.1016/0006-8993(93)90572-5;
RA Chieng B., Howden M.E.H., Christie M.J.;
RT "Australian funnel-web spider toxin, versutoxin, enhances spontaneous
RT synaptic activity in single brain neurons in vitro.";
RL Brain Res. 626:136-142(1993).
RN [3]
RP FUNCTION.
RX PubMed=7816562; DOI=10.1007/bf00724524;
RA Nicholson G.M., Willow M., Howden M.E., Narahashi T.;
RT "Modification of sodium channel gating and kinetics by versutoxin from the
RT Australian funnel-web spider Hadronyche versuta.";
RL Pflugers Arch. 428:400-409(1994).
RN [4]
RP FUNCTION.
RX PubMed=9028001; DOI=10.1016/s0041-0101(96)00089-x;
RA Nicholson G.M., Little M.J., Tyler M.I., Narahashi T.;
RT "Selective alteration of sodium channel gating by Australian funnel-web
RT spider toxins.";
RL Toxicon 34:1443-1453(1996).
RN [5]
RP FUNCTION, AND TOXIC DOSE.
RX PubMed=9845331; DOI=10.1016/s0014-5793(98)01378-7;
RA Little M.J., Wilson H., Zappia C., Cestele S., Tyler M.I.,
RA Martin-Eauclaire M.-F., Gordon D., Nicholson G.M.;
RT "Delta-atracotoxins from Australian funnel-web spiders compete with
RT scorpion alpha-toxin binding on both rat brain and insect sodium
RT channels.";
RL FEBS Lett. 439:246-252(1998).
RN [6]
RP FUNCTION.
RX PubMed=11171353; DOI=10.1242/jeb.204.4.711;
RA Grolleau F., Stankiewicz M., Birinyi-Strachan L., Wang X.H.,
RA Nicholson G.M., Pelhate M., Lapied B.;
RT "Electrophysiological analysis of the neurotoxic action of a funnel-web
RT spider toxin, delta-atracotoxin-HV1a, on insect voltage-gated Na+
RT channels.";
RL J. Exp. Biol. 204:711-721(2001).
RN [7]
RP FUNCTION.
RX PubMed=11874465; DOI=10.1046/j.1432-1033.2002.02799.x;
RA Gilles N., Harrison G., Karbat I., Gurevitz M., Nicholson G.M., Gordon D.;
RT "Variations in receptor site-3 on rat brain and insect sodium channels
RT highlighted by binding of a funnel-web spider delta-atracotoxin.";
RL Eur. J. Biochem. 269:1500-1510(2002).
RN [8]
RP FUNCTION.
RX PubMed=18986214; DOI=10.1371/journal.pbio.0060273;
RA Wu Y., Cao G., Pavlicek B., Luo X., Nitabach M.N.;
RT "Phase coupling of a circadian neuropeptide with rest/activity rhythms
RT detected using a membrane-tethered spider toxin.";
RL PLoS Biol. 6:E273-E273(2008).
RN [9]
RP STRUCTURE BY NMR OF 1-42, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=9384567; DOI=10.1016/s0969-2126(97)00301-8;
RA Fletcher J.I., Chapman B.E., Mackay J.P., Howden M.E.H., King G.F.;
RT "The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into
RT the binding of site 3 neurotoxins to the voltage-gated sodium channel.";
RL Structure 5:1525-1535(1997).
CC -!- FUNCTION: Inhibits tetrodotoxin-sensitive voltage-gated sodium channels
CC (Nav) by binding to site 3. Slows the inactivation, and causes a
CC prolongation of action potential duration resulting in repetitive
CC firing in autonomic and motor nerve fibers. Does not depolarize the
CC resting potential. Does not affect tetrodotoxin-resistant sodium
CC channels. This lethal neurotoxin is active on both insect and mammalian
CC voltage-gated sodium channels. Pan-neuronal expression in Drosophila is
CC lethal but flies engineered to express the toxin only in pacemaker
CC neurons have profound defects in circadian rhythm but a normal
CC lifespan. {ECO:0000269|PubMed:11171353, ECO:0000269|PubMed:11874465,
CC ECO:0000269|PubMed:18986214, ECO:0000269|PubMed:7816562,
CC ECO:0000269|PubMed:8281423, ECO:0000269|PubMed:9028001,
CC ECO:0000269|PubMed:9845331}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:3355530}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:3355530}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:9384567}.
CC -!- MASS SPECTROMETRY: Mass=4847.2; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:9384567};
CC -!- TOXIC DOSE: LD(50) is 0.06 ug/kg by intracerebroventricular injection
CC into mice. {ECO:0000269|PubMed:9845331}.
CC -!- TOXIC DOSE: LD(50) is 0.2 mg/kg by subcutaneous injection into mice.
CC {ECO:0000269|PubMed:9845331}.
CC -!- TOXIC DOSE: LD(50) is 770 pmol/g when injected into crickets.
CC {ECO:0000269|PubMed:9845331}.
CC -!- TOXIC DOSE: PD(50) is 200 +-36 pmol/g when injected into crickets.
CC {ECO:0000269|PubMed:9845331}.
CC -!- TOXIC DOSE: PD(50) is 54 +- 14 pmol/g when injected into blowfly
CC larvae. {ECO:0000269|PubMed:9845331}.
CC -!- MISCELLANEOUS: Is the sole lethal toxin in male and female A.versutus
CC venom.
CC -!- SIMILARITY: Belongs to the neurotoxin 06 (delta-actx) family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR PIR; S00343; NTIIV.
DR PDB; 1VTX; NMR; -; A=1-42.
DR PDBsum; 1VTX; -.
DR AlphaFoldDB; P13494; -.
DR BMRB; P13494; -.
DR SMR; P13494; -.
DR TCDB; 8.B.6.2.1; the ca(2+) channel-targeting spider toxin (cst) family.
DR ArachnoServer; AS000307; delta-hexatoxin-Hv1a.
DR EvolutionaryTrace; P13494; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR008017; Atracotoxin_delta.
DR Pfam; PF05353; Atracotoxin; 1.
DR PROSITE; PS60018; DELTA_ACTX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Neurotoxin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..42
FT /note="Delta-hexatoxin-Hv1a"
FT /evidence="ECO:0000269|PubMed:3355530"
FT /id="PRO_0000087654"
FT DISULFID 1..15
FT /evidence="ECO:0000269|PubMed:9384567,
FT ECO:0000312|PDB:1VTX"
FT DISULFID 8..20
FT /evidence="ECO:0000269|PubMed:9384567,
FT ECO:0000312|PDB:1VTX"
FT DISULFID 14..31
FT /evidence="ECO:0000269|PubMed:9384567,
FT ECO:0000312|PDB:1VTX"
FT DISULFID 16..42
FT /evidence="ECO:0000269|PubMed:9384567,
FT ECO:0000312|PDB:1VTX"
FT STRAND 18..21
FT /evidence="ECO:0007829|PDB:1VTX"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:1VTX"
FT HELIX 35..40
FT /evidence="ECO:0007829|PDB:1VTX"
SQ SEQUENCE 42 AA; 4856 MW; 8CB1CEC225532A4E CRC64;
CAKKRNWCGK TEDCCCPMKC VYAWYNEQGS CQSTISALWK KC
