TXMG5_MACGS
ID TXMG5_MACGS Reviewed; 79 AA.
AC P83561; Q75WH0;
DT 27-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 25-MAY-2022, entry version 78.
DE RecName: Full=Beta-hexatoxin-Mg1a;
DE Short=Beta-HXTX-Mg1a;
DE AltName: Full=Neurotoxin magi-5;
DE Flags: Precursor;
OS Macrothele gigas (Japanese funnel web spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Macrothelidae; Macrothele.
OX NCBI_TaxID=223896;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RA Satake H., Villegas E., Corzo G.;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 51-79, FUNCTION, SUBCELLULAR LOCATION, TOXIC DOSE, AND
RP MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=12860384; DOI=10.1016/s0014-5793(03)00666-5;
RA Corzo G., Gilles N., Satake H., Villegas E., Dai L., Nakajima T., Haupt J.;
RT "Distinct primary structures of the major peptide toxins from the venom of
RT the spider Macrothele gigas that bind to sites 3 and 4 in the sodium
RT channel.";
RL FEBS Lett. 547:43-50(2003).
RN [3]
RP STRUCTURE BY NMR OF 51-79, DISULFIDE BONDS, SYNTHESIS, AND ALANINE-SCANNING
RP MUTAGENESIS.
RX PubMed=17148449; DOI=10.1074/jbc.m605403200;
RA Corzo G., Sabo J.K., Bosmans F., Billen B., Villegas E., Tytgat J.,
RA Norton R.S.;
RT "Solution structure and alanine scan of a spider toxin that affects the
RT activation of mammalian voltage-gated sodium channels.";
RL J. Biol. Chem. 282:4643-4652(2007).
CC -!- FUNCTION: Insect and vertebrate active toxin. Binds to site 4 of
CC mammalian voltage-gated sodium channels and shifts the activation
CC voltage of the mammalian Nav1.2a/SCN2A channel to more hyperpolarized
CC voltages, whereas the insect channel, DmNav1 (para), is not affected.
CC Competes for binding at site 3 of the insect sodium channel. Causes
CC temporary paralysis when injected into lepidopteran larvae at 8.6
CC nmol/g. A low intracranial injection dose into mice causes lacrimation,
CC closure of the eyes and sweating. A high injection dose causes
CC extensive lacrimation and death. {ECO:0000269|PubMed:12860384}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12860384}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:12860384}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin. {ECO:0000255}.
CC -!- MASS SPECTROMETRY: Mass=3286.8; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:12860384};
CC -!- TOXIC DOSE: LD(50) is 0.73 pmol/g by intracranial injection into mice.
CC {ECO:0000269|PubMed:12860384}.
CC -!- MISCELLANEOUS: The primary structure of the mature toxin is identical
CC to that of beta-hexatoxin-Mr1a (Raventoxin-III) from Macrothele raveni
CC (AC P61232).
CC -!- SIMILARITY: Belongs to the neurotoxin 15 family. 01 (magi-5) subfamily.
CC {ECO:0000305}.
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DR EMBL; AB121201; BAD13408.1; -; mRNA.
DR PDB; 2GX1; NMR; -; A=51-79.
DR PDBsum; 2GX1; -.
DR AlphaFoldDB; P83561; -.
DR SMR; P83561; -.
DR ArachnoServer; AS000384; beta-hexatoxin-Mg1a.
DR EvolutionaryTrace; P83561; -.
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; IPR012628; Toxin_23.
DR Pfam; PF08093; Toxin_23; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..50
FT /evidence="ECO:0000269|PubMed:12860384,
FT ECO:0000269|PubMed:17148449"
FT /id="PRO_0000035588"
FT PEPTIDE 51..79
FT /note="Beta-hexatoxin-Mg1a"
FT /evidence="ECO:0000269|PubMed:12860384"
FT /id="PRO_0000035589"
FT DISULFID 52..66
FT /evidence="ECO:0000269|PubMed:17148449"
FT DISULFID 59..71
FT /evidence="ECO:0000269|PubMed:17148449"
FT DISULFID 65..76
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 55
FT /note="T->A: Decrease in activity."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 56
FT /note="F->A: Decrease in activity."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 56
FT /note="F->Y: Loss of activity on Nav1.2."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 57
FT /note="W->A,Y: Decrease in activity."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 58
FT /note="K->A: No change in activity."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 60
FT /note="K->A: Loss of activity on Nav1.2."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 61
FT /note="N->A: No change in activity."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 62
FT /note="K->A: Decrease in activity."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 63
FT /note="K->A: No change in activity."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 64
FT /note="E->A: Loss of activity on Nav1.2."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 68
FT /note="W->A,F: Loss of activity on Nav1.2."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 68
FT /note="W->Y: Decrease in activity."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 69
FT /note="N->A: Loss of activity on Nav1.2."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 73
FT /note="L->A: Decrease in activity."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 75
FT /note="I->A: Loss of activity on Nav1.2."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 77
FT /note="M->A: Loss of activity on Nav1.2."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 78
FT /note="P->A: Loss of activity on Nav1.2."
FT /evidence="ECO:0000269|PubMed:17148449"
FT MUTAGEN 79
FT /note="R->A: Important increase in activity."
FT /evidence="ECO:0000269|PubMed:17148449"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:2GX1"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:2GX1"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:2GX1"
SQ SEQUENCE 79 AA; 8791 MW; 1C07F3B96D5AA901 CRC64;
MKAPATTLIL VMSLISVLWA TPDLEEGDLL AELGDLIATD DEYPMKPEER GCKLTFWKCK
NKKECCGWNA CALGICMPR
