TXI92_DIGCA
ID TXI92_DIGCA Reviewed; 94 AA.
AC P49126;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 25-MAY-2022, entry version 83.
DE RecName: Full=Beta-diguetoxin-Dc1a {ECO:0000303|PubMed:25014760};
DE Short=Beta-DGTX-Dc1a {ECO:0000303|PubMed:25014760};
DE Short=Dc1a {ECO:0000303|PubMed:30049784};
DE AltName: Full=Insecticidal toxin DTX9.2 {ECO:0000303|PubMed:8541888, ECO:0000303|PubMed:8896202};
DE Flags: Precursor;
OS Diguetia canities (Desert bush spider) (Segestria canities).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Pholcoidea; Diguetidae; Diguetia.
OX NCBI_TaxID=38407;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 39-71, FUNCTION, MASS
RP SPECTROMETRY, AND TOXIC DOSE.
RC TISSUE=Venom gland;
RX PubMed=8541888; DOI=10.1016/0965-1748(95)00029-u;
RA Krapcho K.J., Kral R.M. Jr., Vanwagenen B.C., Eppler K.G., Morgan T.K.;
RT "Characterization and cloning of insecticidal peptides from the primitive
RT weaving spider Diguetia canities.";
RL Insect Biochem. Mol. Biol. 25:991-1000(1995).
RN [2]
RP FUNCTION.
RX PubMed=8896202; DOI=10.1016/0041-0101(96)00028-1;
RA Bloomquist J.R., Kinne L.P., Deutsch V., Simpson S.F.;
RT "Mode of action of an insecticidal peptide toxin from the venom of a
RT weaving spider (Diguetia canities).";
RL Toxicon 34:1072-1075(1996).
RN [3] {ECO:0000312|PDB:2MI5}
RP STRUCTURE BY NMR OF 39-94, FUNCTION, AND TOXIC DOSE.
RX PubMed=25014760; DOI=10.1038/ncomms5350;
RA Bende N.S., Dziemborowicz S., Mobli M., Herzig V., Gilchrist J., Wagner J.,
RA Nicholson G.M., King G.F., Bosmans F.;
RT "A distinct sodium channel voltage-sensor locus determines insect
RT selectivity of the spider toxin Dc1a.";
RL Nat. Commun. 5:4350-4359(2014).
RN [4] {ECO:0000312|PDB:6A90, ECO:0000312|PDB:6A91, ECO:0000312|PDB:6A95}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.6 ANGSTROMS) IN COMPLEX WITH AMERICAN
RP COCKROACH NAV; SAXITOXIN AND TETRODOTOXIN, DISULFIDE BOND, AND MUTAGENESIS
RP OF ASP-58; TYR-70; ARG-78; LYS-81; PHE-84; PHE-85; SER-86 AND ASP-93.
RX PubMed=30049784; DOI=10.1126/science.aau2596;
RA Shen H., Li Z., Jiang Y., Pan X., Wu J., Cristofori-Armstrong B.,
RA Smith J.J., Chin Y.K.Y., Lei J., Zhou Q., King G.F., Yan N.;
RT "Structural basis for the modulation of voltage-gated sodium channels by
RT animal toxins.";
RL Science 362:0-0(2018).
CC -!- FUNCTION: Insecticidal toxin (PubMed:8541888, PubMed:8896202). This
CC toxin promotes opening of insect Nav channels. The toxin binds to the
CC S1-S2 and S3-S4 loops in the domain II voltage-sensor of insect Nav
CC channels (i.e., receptor site 4). The American cockroach P.americana is
CC largely resistant to the effects of this toxin due to an unusual
CC sequence within the domain II S1-S2 loop. In vivo, paralyzes
CC lepidopteran and dipteran larvae. Paralyzed insects ultimately die from
CC secondary effects of starvation and dehydration (PubMed:25014760).
CC {ECO:0000269|PubMed:25014760, ECO:0000269|PubMed:8541888,
CC ECO:0000269|PubMed:8896202}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8541888}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:25014760, ECO:0000269|PubMed:30049784}.
CC -!- MASS SPECTROMETRY: Mass=6371; Mass_error=2; Method=FAB;
CC Evidence={ECO:0000269|PubMed:8541888};
CC -!- TOXIC DOSE: PD(50) is 0.38 nmol/g in lepidopteran larvae.
CC {ECO:0000269|PubMed:8541888}.
CC -!- TOXIC DOSE: LD(50) is 0.231 +- 32 nmol/g in blowfly adult (L.cuprina).
CC {ECO:0000269|PubMed:25014760}.
CC -!- TOXIC DOSE: LD(50) is 0.493 nmol/g in adult housefly (Musca domestica).
CC {ECO:0000269|PubMed:25014760}.
CC -!- MISCELLANEOUS: This toxin has no effect on the human Nav channel
CC subtypes Nav1.1-Nav1.7, and no effect on hERG (Kv11.1) and Kv2.1. Is
CC non-toxic to mice at 657 pmol/g (4.2 mg/kg) i.p. and 156 pmol/g (1.0
CC mg/kg) i.c.v. {ECO:0000269|PubMed:25014760}.
CC -!- SIMILARITY: Belongs to the neurotoxin 26 (DTX) family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Electron Microscopy Data Bank (EMDB);
CC URL="https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-6995";
CC -!- WEB RESOURCE: Name=Electron Microscopy Data Bank (EMDB);
CC URL="https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-6996";
CC -!- WEB RESOURCE: Name=Electron Microscopy Data Bank (EMDB);
CC URL="https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-6997";
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DR EMBL; U21904; AAB60253.1; -; mRNA.
DR PDB; 2MI5; NMR; -; A=39-94.
DR PDB; 6A90; EM; 2.80 A; B=39-94.
DR PDB; 6A91; EM; 3.20 A; B=39-94.
DR PDB; 6A95; EM; 2.60 A; B=39-94.
DR PDBsum; 2MI5; -.
DR PDBsum; 6A90; -.
DR PDBsum; 6A91; -.
DR PDBsum; 6A95; -.
DR AlphaFoldDB; P49126; -.
DR BMRB; P49126; -.
DR SMR; P49126; -.
DR IntAct; P49126; 1.
DR TCDB; 8.B.30.1.1; the diguetoxin (diguetoxin) family.
DR ArachnoServer; AS000352; mu-diguetoxin-Dc1a.
DR GO; GO:0005576; C:extracellular region; 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 InterPro; IPR035290; Beta/Mu-DGTX-Dc1.
DR Pfam; PF17491; m_DGTX_Dc1a_b_c; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Neurotoxin; Presynaptic neurotoxin;
KW Secreted; Signal; Toxin; Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT PROPEP 18..38
FT /evidence="ECO:0000269|PubMed:8541888"
FT /id="PRO_0000035542"
FT CHAIN 39..94
FT /note="Beta-diguetoxin-Dc1a"
FT /id="PRO_0000035543"
FT SITE 58
FT /note="Interacts with insect Nav channel"
FT /evidence="ECO:0000269|PubMed:30049784"
FT SITE 70
FT /note="Interacts with insect Nav channel"
FT /evidence="ECO:0000269|PubMed:30049784"
FT SITE 78
FT /note="Interacts with insect Nav channel"
FT /evidence="ECO:0000269|PubMed:30049784"
FT SITE 81
FT /note="Interacts with insect Nav channel"
FT /evidence="ECO:0000269|PubMed:30049784"
FT SITE 85
FT /note="Interacts with insect Nav channel"
FT /evidence="ECO:0000269|PubMed:30049784"
FT SITE 86
FT /note="Interacts with insect Nav channel"
FT /evidence="ECO:0000269|PubMed:30049784"
FT SITE 93
FT /note="Interacts with insect Nav channel"
FT /evidence="ECO:0000269|PubMed:30049784"
FT DISULFID 50..63
FT /evidence="ECO:0000269|PubMed:25014760,
FT ECO:0000269|PubMed:30049784, ECO:0007744|PDB:2MI5,
FT ECO:0007744|PDB:6A90, ECO:0007744|PDB:6A91,
FT ECO:0007744|PDB:6A95"
FT DISULFID 57..77
FT /evidence="ECO:0000269|PubMed:25014760,
FT ECO:0000269|PubMed:30049784, ECO:0007744|PDB:2MI5,
FT ECO:0007744|PDB:6A90, ECO:0007744|PDB:6A91,
FT ECO:0007744|PDB:6A95"
FT DISULFID 62..91
FT /evidence="ECO:0000269|PubMed:25014760,
FT ECO:0000269|PubMed:30049784, ECO:0007744|PDB:2MI5,
FT ECO:0007744|PDB:6A90, ECO:0007744|PDB:6A91"
FT DISULFID 79..89
FT /evidence="ECO:0000269|PubMed:25014760,
FT ECO:0000269|PubMed:30049784, ECO:0007744|PDB:2MI5,
FT ECO:0007744|PDB:6A90, ECO:0007744|PDB:6A91,
FT ECO:0007744|PDB:6A95"
FT VARIANT 64
FT /note="Q -> T"
FT MUTAGEN 58
FT /note="D->A: Almost complete loss of activation of
FT B.germanica sodium channel."
FT /evidence="ECO:0000269|PubMed:30049784"
FT MUTAGEN 70
FT /note="Y->A: Almost complete loss of activation of
FT B.germanica sodium channel."
FT /evidence="ECO:0000269|PubMed:30049784"
FT MUTAGEN 78
FT /note="R->A: Almost complete loss of activation of
FT B.germanica sodium channel."
FT /evidence="ECO:0000269|PubMed:30049784"
FT MUTAGEN 81
FT /note="K->A: Almost complete loss of activation of
FT B.germanica sodium channel."
FT /evidence="ECO:0000269|PubMed:30049784"
FT MUTAGEN 84
FT /note="F->A: Severe decrease of activation of B.germanica
FT sodium channel."
FT /evidence="ECO:0000269|PubMed:30049784"
FT MUTAGEN 85
FT /note="F->A: Severe decrease of activation of B.germanica
FT sodium channel."
FT /evidence="ECO:0000269|PubMed:30049784"
FT MUTAGEN 86
FT /note="S->A: Severe decrease of activation of B.germanica
FT sodium channel."
FT /evidence="ECO:0000269|PubMed:30049784"
FT MUTAGEN 93
FT /note="D->A: Almost complete loss of activation of
FT B.germanica sodium channel."
FT /evidence="ECO:0000269|PubMed:30049784"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:6A90"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:6A95"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:6A95"
FT STRAND 69..81
FT /evidence="ECO:0007829|PDB:6A95"
FT STRAND 87..93
FT /evidence="ECO:0007829|PDB:6A95"
SQ SEQUENCE 94 AA; 10672 MW; 715177022DCEAB2D CRC64;
MKVFVVLLCL SLAAVYALEE RLDKDADIML DSPADMERAK DGDVEGPAGC KKYDVECDSG
ECCQKQYLWY KWRPLDCRCL KSGFFSSKCV CRDV
