TO1A_HADVE
ID TO1A_HADVE Reviewed; 37 AA.
AC P56207;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 25-MAY-2022, entry version 98.
DE RecName: Full=Omega-hexatoxin-Hv1a {ECO:0000305};
DE Short=Omega-HXTX-Hv1a {ECO:0000305};
DE AltName: Full=Omega-atracotoxin-Hv1a {ECO:0000303|PubMed:10491095};
DE Short=Omega-ACTX-Hv1 {ECO:0000303|PubMed:9228949};
DE Short=Omega-AcTx-Hv1a {ECO:0000303|PubMed:10491095};
DE Short=Omega-atracotoxin-Hv1 {ECO:0000303|PubMed:9228949};
DE AltName: Full=Omega/kappa-atracotoxin-Hv1a {ECO:0000303|Ref.13};
DE Short=Omega/kappa-HXTX-Hv1a {ECO:0000303|Ref.13};
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, SYNTHESIS, TOXIC DOSE, STRUCTURE BY NMR, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom;
RX PubMed=9228949; DOI=10.1038/nsb0797-559;
RA Fletcher J.I., Smith R., O'Donoghue S.I., Nilges M., Connor M.,
RA Howden M.E.H., Christie M.J., King G.F.;
RT "The structure of a novel insecticidal neurotoxin, omega-atracotoxin-HV1,
RT from the venom of an Australian funnel web spider.";
RL Nat. Struct. Biol. 4:559-566(1997).
RN [2]
RP TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=10491095; DOI=10.1046/j.1432-1327.1999.00646.x;
RA Wang X.-H., Smith R., Fletcher J.I., Wilson H., Wood C.J., Merlin E.H.,
RA King G.F.;
RT "Structure-function studies of omega-atracotoxin, a potent antagonist of
RT insect voltage-gated calcium channels.";
RL Eur. J. Biochem. 264:488-494(1999).
RN [3]
RP FUNCTION.
RX PubMed=14608494; DOI=10.1007/s10158-003-0027-z;
RA Bloomquist J.R.;
RT "Mode of action of atracotoxin at central and peripheral synapses of
RT insects.";
RL Invertebr. Neurosci. 5:45-50(2003).
RN [4]
RP FUNCTION, TOXIC DOSE, AND MUTAGENESIS OF GLN-9; PRO-10; ASN-27 AND ARG-35.
RX PubMed=15308644; DOI=10.1074/jbc.m404006200;
RA Tedford H.W., Gilles N., Menez A., Doering C.J., Zamponi G.W., King G.F.;
RT "Scanning mutagenesis of omega-atracotoxin-Hv1a reveals a spatially
RT restricted epitope that confers selective activity against insect calcium
RT channels.";
RL J. Biol. Chem. 279:44133-44140(2004).
RN [5]
RP FUNCTION, AND TOXIC DOSE.
RX PubMed=16330063; DOI=10.1016/j.toxicon.2005.10.011;
RA Mukherjee A.K., Sollod B.L., Wikel S.K., King G.F.;
RT "Orally active acaricidal peptide toxins from spider venom.";
RL Toxicon 47:182-187(2006).
RN [6]
RP TRANSGENIC PROTECTION OF PLANTS.
RX PubMed=16779650; DOI=10.1007/s11248-006-0007-2;
RA Khan S.A., Zafar Y., Briddon R.W., Malik K.A., Mukhtar Z.;
RT "Spider venom toxin protects plants from insect attack.";
RL Transgenic Res. 15:349-357(2006).
RN [7]
RP FUNCTION.
RC STRAIN=XenFW194; TISSUE=Venom, and Venom gland;
RX PubMed=17610847; DOI=10.1016/j.bcp.2007.05.017;
RA Chong Y., Hayes J.L., Sollod B., Wen S., Wilson D.T., Hains P.G.,
RA Hodgson W.C., Broady K.W., King G.F., Nicholson G.M.;
RT "The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium
RT channels.";
RL Biochem. Pharmacol. 74:623-638(2007).
RN [8]
RP FUNCTION.
RX PubMed=17141372; DOI=10.1016/j.peptides.2006.08.026;
RA Tedford H.W., Maggio F., Reenan R.A., King G.;
RT "A model genetic system for testing the in vivo function of peptide
RT toxins.";
RL Peptides 28:51-56(2007).
RN [9]
RP BIOTECHNOLOGY, AND RECOMBINANT EXPRESSION AS A CHIMERIC VARIANT.
RX PubMed=22761779; DOI=10.1371/journal.pone.0039389;
RA Fitches E.C., Pyati P., King G.F., Gatehouse J.A.;
RT "Fusion to snowdrop lectin magnifies the oral activity of insecticidal
RT omega-Hexatoxin-Hv1a peptide by enabling its delivery to the central
RT nervous system.";
RL PLoS ONE 7:e39389-e39389(2012).
RN [10]
RP BIOTECHNOLOGY, AND RECOMBINANT EXPRESSION AS A CHIMERIC VARIANT.
RX PubMed=24316580; DOI=10.1038/nbt.2753;
RA Bonning B.C., Pal N., Liu S., Wang Z., Sivakumar S., Dixon P.M., King G.F.,
RA Miller W.A.;
RT "Toxin delivery by the coat protein of an aphid-vectored plant virus
RT provides plant resistance to aphids.";
RL Nat. Biotechnol. 32:102-105(2014).
RN [11]
RP BIOTECHNOLOGY, AND RECOMBINANT EXPRESSION AS A CHIMERIC VARIANT.
RX PubMed=24898372; DOI=10.1098/rspb.2014.0619;
RA Nakasu E.Y., Williamson S.M., Edwards M.G., Fitches E.C., Gatehouse J.A.,
RA Wright G.A., Gatehouse A.M.;
RT "Novel biopesticide based on a spider venom peptide shows no adverse
RT effects on honeybees.";
RL Proc. R. Soc. B 281:1-9(2014).
RN [12]
RP TOXIC DOSE.
RX PubMed=27383378; DOI=10.1038/srep29538;
RA Herzig V., Ikonomopoulou M., Smith J.J., Dziemborowicz S., Gilchrist J.,
RA Kuhn-Nentwig L., Rezende F.O., Moreira L.A., Nicholson G.M., Bosmans F.,
RA King G.F.;
RT "Molecular basis of the remarkable species selectivity of an insecticidal
RT sodium channel toxin from the African spider Augacephalus ezendami.";
RL Sci. Rep. 6:29538-29538(2016).
RN [13]
RP BIOTECHNOLOGY.
RX DOI=10.1007/s10340-018-1016-7;
RA Fanning P.D., VanWoerkom A., Wise J.C., Isaacs R.;
RT "Assessment of a commercial spider venom peptide against spotted-wing
RT Drosophila and interaction with adjuvants.";
RL J. Pest Sci. 4:1279-1290(2018).
RN [14]
RP BIOTECHNOLOGY.
RX PubMed=31997983; DOI=10.1007/s10340-019-01143-3;
RA Powell M.E., Bradish H.M., Cao M., Makinson R., Brown A.P., Gatehouse J.A.,
RA Fitches E.C.;
RT "Demonstrating the potential of a novel spider venom-based biopesticide for
RT target-specific control of the small hive beetle, a serious pest of the
RT European honeybee.";
RL J. Pest Sci. 93:391-402(2020).
RN [15]
RP STRUCTURE BY NMR OF 4-23, TOXIC DOSE, AND MUTAGENESIS OF ASN-27 AND ARG-35.
RX PubMed=11313356; DOI=10.1074/jbc.m102199200;
RA Tedford H.W., Fletcher J.I., King G.F.;
RT "Functional significance of the beta hairpin in the insecticidal neurotoxin
RT omega-atracotoxin-Hv1a.";
RL J. Biol. Chem. 276:26568-26576(2001).
CC -!- FUNCTION: Reversibly and voltage-independently blocks both mid-low- (M-
CC LVA) and high-voltage-activated (HVA) calcium channels in cockroach DUM
CC neurons (PubMed:17610847). Is lethal to many insect species but not
CC toxic to mammals (PubMed:9228949, PubMed:16779650). May target the
CC insect high-voltage-activated calcium channel Dmca1D. Also inhibits
CC acarines calcium channels. An extremely high toxin concentration
CC partially inhibits Cav1.2/CACNA1C, Cav2.1/CACNA1A and Cav2.2/CACNA1B
CC calcium channel of rats. As for omega-AcTx-Hv2a, the phenotypic effect
CC of injection of this toxin into lone star ticks (Amblyomma americanum)
CC is curling of all eight legs into closed loops.
CC {ECO:0000269|PubMed:14608494, ECO:0000269|PubMed:15308644,
CC ECO:0000269|PubMed:16330063, ECO:0000269|PubMed:17141372,
CC ECO:0000269|PubMed:17610847, ECO:0000269|PubMed:9228949}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9228949}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:9228949}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:11313356, ECO:0000269|PubMed:9228949}.
CC -!- TOXIC DOSE: PD(50) is 3 umol/kg in tobacco budworms (Heliothis
CC armigera). {ECO:0000305|PubMed:9228949}.
CC -!- TOXIC DOSE: PD(50) is 0.25 umol/kg in tobacco budworms (Heliothis
CC virescens). {ECO:0000305|PubMed:9228949}.
CC -!- TOXIC DOSE: LD(50) is 89-91 pmol/g (0.38 mg/kg) to house crickets
CC (Acheta domesticus). {ECO:0000269|PubMed:10491095}.
CC -!- TOXIC DOSE: LD(50) is 86.5 pmol/g in house flies (Musca domestica).
CC {ECO:0000269|PubMed:10491095}.
CC -!- TOXIC DOSE: LD(50) is 716 +-23 pmol/g (3.00 +-0.10 ug/g) when orally
CC administered into lone star ticks (Amblyomma americanum).
CC -!- TOXIC DOSE: LD(50) is 447 +-3 pmol/g (1877 +-0.013 ug/g) when injected
CC into lone star ticks (Amblyomma americanum).
CC -!- TOXIC DOSE: LD(50) is 147 nmol/g in triatomine bug (Rhodinius
CC prolixus). {ECO:0000269|PubMed:27383378}.
CC -!- TOXIC DOSE: PD(50) is 0.32 umol/kg in Periplaneta americana.
CC {ECO:0000269|PubMed:9228949}.
CC -!- BIOTECHNOLOGY: Spear and Spear T (Vesparon) are biological insecticides
CC containing 20% of the active ingredient GS-omega/kappa-Hxtx-Hv1a. They
CC are effective against thrips, whiteflies, and spider mites in
CC greenhouse settings. They have a large molecular weight, are
CC hydrophilic, and have many hydrogen donors. They kill some insects on
CC contact. The peptides block two ion channels in the insect nervous
CC system (a voltage-gated calcium channel (Cav) and a calcium-activated
CC potassium channel (KCa)). {ECO:0000269|Ref.13}.
CC -!- BIOTECHNOLOGY: Could be considered as a biological insecticide
CC candidate, when fused to Galanthus nivalis agglutinin (GNA), a protein
CC with the potential to cross the insect gut (PubMed:22761779). This
CC chimeric Hv1a/GNA variant shows a gain in toxicity on insects when
CC administered orally (tested on Mamestra brassicae), while maintaining
CC similar effects as the wild-type toxin when injected (PubMed:22761779).
CC Transport of fusion protein from gut contents to the hemolymph of
CC insect larvae, and binding to the nerve chord indicate that the fusion
CC with GNA permits to deliver the toxin to sites of action within the
CC insect central nervous system (PubMed:22761779). The Hv1a/GNA variant
CC does not show adverse effects on honeybees (PubMed:22761779,
CC PubMed:24898372). {ECO:0000269|PubMed:22761779,
CC ECO:0000269|PubMed:24898372}.
CC -!- BIOTECHNOLOGY: Potential biopesticide that could protect honeybees from
CC the parasitic small hive beetle pest Aethina tumida, but is harmless to
CC honeybees. Is orally toxic to A.tumida, when fused to Galanthus nivalis
CC agglutinin (GNA), a protein with the potential to cross the insect gut.
CC {ECO:0000269|PubMed:22761779}.
CC -!- BIOTECHNOLOGY: Could be considered as a biological insecticide
CC candidate, when fused to a luteovirus coat protein, which is able for
CC delivery of fused proteins into the hemocoel of pea aphids. This
CC luteovirus coat protein is used as a carrier to greatly enhance the
CC oral toxicity of Hv1a to a range of aphid pest species (Acyrthosiphon
CC pisum, Rhopalosiphum padi, Aphis glycines and Myzus persicae).
CC {ECO:0000269|PubMed:24316580}.
CC -!- MISCELLANEOUS: When expressed in tobacco plants, the toxin induces a
CC 100% mortality of insect larvae H.armigera and S.littoralis after
CC ingestion. {ECO:0000269|PubMed:16779650}.
CC -!- SIMILARITY: Belongs to the neurotoxin 08 (Shiva) family. 01 (omega
CC toxin) subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Chemical and engineering news;
CC URL="https://cen.acs.org/articles/95/i11/Spider-venom-insecticide-whose-time.html";
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DR PDB; 1AXH; NMR; -; A=1-37.
DR PDB; 1HVW; NMR; -; A=4-23.
DR PDBsum; 1AXH; -.
DR PDBsum; 1HVW; -.
DR AlphaFoldDB; P56207; -.
DR BMRB; P56207; -.
DR SMR; P56207; -.
DR ArachnoServer; AS000193; omega-hexatoxin-Hv1a.
DR EvolutionaryTrace; P56207; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019855; F:calcium channel inhibitor activity; IDA:CACAO.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006952; P:defense response; IEA:InterPro.
DR InterPro; IPR009415; Omega-atracotox.
DR InterPro; IPR018071; Omega-atracotox_CS.
DR Pfam; PF06357; Omega-toxin; 1.
DR PROSITE; PS60016; OMEGA_ACTX_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium channel impairing toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin; Secreted;
KW Toxin; Voltage-gated calcium channel impairing toxin.
FT PEPTIDE 1..37
FT /note="Omega-hexatoxin-Hv1a"
FT /evidence="ECO:0000269|PubMed:9228949"
FT /id="PRO_0000044988"
FT SITE 10
FT /note="Critical for insecticidal activity"
FT /evidence="ECO:0000305|PubMed:15308644"
FT SITE 27
FT /note="Critical for insecticidal activity"
FT /evidence="ECO:0000305|PubMed:15308644"
FT SITE 35
FT /note="Critical for insecticidal activity"
FT /evidence="ECO:0000305|PubMed:15308644"
FT DISULFID 4..18
FT /evidence="ECO:0000269|PubMed:11313356,
FT ECO:0000269|PubMed:9228949, ECO:0000312|PDB:1AXH,
FT ECO:0000312|PDB:1HVW"
FT DISULFID 11..22
FT /evidence="ECO:0000269|PubMed:11313356,
FT ECO:0000269|PubMed:9228949, ECO:0000312|PDB:1AXH,
FT ECO:0000312|PDB:1HVW"
FT DISULFID 17..36
FT /evidence="ECO:0000269|PubMed:11313356,
FT ECO:0000269|PubMed:9228949, ECO:0000312|PDB:1AXH,
FT ECO:0000312|PDB:1HVW"
FT MUTAGEN 9
FT /note="Q->A: 4-fold decrease in toxicity to crickets, and
FT insignificant decrease to flies. 16-fold decrease in
FT binding affinity to cockroach membranes."
FT /evidence="ECO:0000269|PubMed:15308644"
FT MUTAGEN 10
FT /note="P->A: 6-fold decrease in toxicity to crickets and
FT 15-fold to flies. 190-fold decrease in binding affinity to
FT cockroach membranes."
FT /evidence="ECO:0000269|PubMed:15308644"
FT MUTAGEN 13
FT /note="Y->A: 16-fold decrease in binding affinity to
FT cockroach membranes."
FT MUTAGEN 27
FT /note="N->A: 14-fold decrease in toxicity to crickets and
FT 30-fold to flies. Abolishes toxicity to crickets and flies;
FT when associated with A-35. 195-fold decrease in binding
FT affinity to cockroach membranes."
FT /evidence="ECO:0000269|PubMed:11313356,
FT ECO:0000269|PubMed:15308644"
FT MUTAGEN 27
FT /note="N->D: 12-fold decrease in toxicity to crickets."
FT /evidence="ECO:0000269|PubMed:11313356,
FT ECO:0000269|PubMed:15308644"
FT MUTAGEN 35
FT /note="R->A: 4.4-fold decrease in toxicity to crickets, and
FT 15 to flies. Abolishes toxicity to crickets and flies; when
FT associated with A-27. 280-fold decrease in binding affinity
FT to cockroach membranes."
FT /evidence="ECO:0000269|PubMed:11313356,
FT ECO:0000269|PubMed:15308644"
FT MUTAGEN 35
FT /note="R->E: 7.8-fold decrease in toxicity to crickets."
FT /evidence="ECO:0000269|PubMed:11313356,
FT ECO:0000269|PubMed:15308644"
FT HELIX 14..16
FT /evidence="ECO:0007829|PDB:1AXH"
FT STRAND 17..20
FT /evidence="ECO:0007829|PDB:1AXH"
FT STRAND 22..26
FT /evidence="ECO:0007829|PDB:1AXH"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:1AXH"
FT STRAND 32..36
FT /evidence="ECO:0007829|PDB:1AXH"
SQ SEQUENCE 37 AA; 4055 MW; A115058BA4364D2F CRC64;
SPTCIPSGQP CPYNENCCSQ SCTFKENENG NTVKRCD
