TXS2B_HORWA
ID TXS2B_HORWA Reviewed; 75 AA.
AC P0DJ08; F8W670;
DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 25-MAY-2022, entry version 20.
DE RecName: Full=Phi-liotoxin-Lw1a;
DE Short=Phi-LITX-Lw1a;
DE AltName: Full=U1-liotoxin-Lw1a;
DE Short=U1-LITX-Lw1a;
DE Flags: Precursor;
OS Hormurus waigiensis (Australian rainforest scorpion) (Liocheles
OS waigiensis).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Scorpionoidea; Hormuridae; Hormurus.
OX NCBI_TaxID=2900493;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 40-75, SYNTHESIS OF 40-75,
RP FUNCTION, BIOASSAY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, TOXIC
RP DOSE, DISULFIDE BOND, MASS SPECTROMETRY, AND STRUCTURE BY NMR OF 40-75.
RC TISSUE=Venom, and Venom gland;
RX PubMed=21670253; DOI=10.1073/pnas.1103501108;
RA Smith J.J., Hill J.M., Little M.J., Nicholson G.M., King G.F.,
RA Alewood P.F.;
RT "Unique scorpion toxin with a putative ancestral fold provides insight into
RT evolution of the inhibitor cystine knot motif.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:10478-10483(2011).
RN [2]
RP FUNCTION, SYNTHESIS OF 40-75, AND MUTAGENESIS OF TRP-75.
RC TISSUE=Venom;
RX PubMed=23671114; DOI=10.1073/pnas.1214062110;
RA Smith J.J., Vetter I., Lewis R.J., Peigneur S., Tytgat J., Lam A.,
RA Gallant E.M., Beard N.A., Alewood P.F., Dulhunty A.F.;
RT "Multiple actions of phi-LITX-Lw1a on ryanodine receptors reveal a
RT functional link between scorpion DDH and ICK toxins.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:8906-8911(2013).
CC -!- FUNCTION: Affects the activity of both ryanodine-sensitive calcium-
CC release channels RyR1 and RyR2 with high potency. At lower
CC concentrations the toxin increases full openings of the RyRs, and at
CC higher concentrations it inhibits full openings and induce openings to
CC subconductance levels and reduces the number of full conductance
CC openings. The different actions may be attributed to the toxins binding
CC at different sites on the RyRs, with binding at a high-affinity site
CC mediating the increase in full openings and the induction of
CC subconductance states evoked upon binding to a lower-affinity site.
CC Insect-selective toxin that provokes a dose-dependent contractile
CC paralysis in crickets and blowfly larvae, followed by death.
CC {ECO:0000269|PubMed:21670253, ECO:0000269|PubMed:23671114}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21670253}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000269|PubMed:21670253}.
CC -!- DOMAIN: Structure of this peptide is made of two-stranded beta-sheets
CC (or DDH for disulfide-directed beta-hairpin) that is uncommon for a
CC scorpion-venom peptide, since it does not contain the CSalpha/beta,
CC CSalpha/alpha, or knottin motif common to other disulfide-rich scorpion
CC toxins. This structure may be the evolutionary precursor to the knottin
CC motif. {ECO:0000269|PubMed:21670253}.
CC -!- MASS SPECTROMETRY: Mass=4171.91; Method=Electrospray; Note=Monoisotopic
CC mass.; Evidence={ECO:0000269|PubMed:21670253};
CC -!- TOXIC DOSE: LD(50) is 784 pmol/g of when injected into mealworm, LD(50)
CC is 1284 pmol/g of when injected into cricket, LD(50) is 4382 pmol/g of
CC when injected into blowfly larvae, LD(50) is 4995 pmol/g of when
CC injected into blowfly adult. {ECO:0000269|PubMed:21670253}.
CC -!- MISCELLANEOUS: Phi-liotoxin-Lw1a may reach its physiological target by
CC traversing membranes, which may be by slow permeation. Alternatively,
CC scorpion venoms are known to contain amphipathic helical peptides that
CC form pores in the cell membrane, and it is possible that these pores
CC would allow Phi-liotoxin-Lw1a to enter the cell (PubMed:23671114).
CC {ECO:0000305|PubMed:23671114}.
CC -!- MISCELLANEOUS: Has no significant effects on sodium (Nav), potassium
CC (Kv) and calcium (Cav) currents (PubMed:21670253 and PubMed:23671114).
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DR PDB; 2KYJ; NMR; -; A=40-75.
DR PDBsum; 2KYJ; -.
DR AlphaFoldDB; P0DJ08; -.
DR BMRB; P0DJ08; -.
DR SMR; P0DJ08; -.
DR TCDB; 8.B.20.1.1; the australian scorpion toxin (liotoxin) family.
DR EvolutionaryTrace; P0DJ08; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium channel impairing toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin;
KW Ryanodine-sensitive calcium-release channel impairing toxin; Secreted;
KW Signal; Toxin.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..39
FT /evidence="ECO:0000269|PubMed:21670253"
FT /id="PRO_0000413155"
FT CHAIN 40..75
FT /note="Phi-liotoxin-Lw1a"
FT /id="PRO_0000413156"
FT DISULFID 50..62
FT /evidence="ECO:0000269|PubMed:21670253"
FT DISULFID 56..68
FT /evidence="ECO:0000269|PubMed:21670253"
FT MUTAGEN 75
FT /note="W->A: Does not induce the full openings seen with
FT the wild-type toxin."
FT /evidence="ECO:0000269|PubMed:23671114"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:2KYJ"
SQ SEQUENCE 75 AA; 8497 MW; D0F60B2AE6B51284 CRC64;
MNFATKVSLL LLAIAVIVIV EGGEGDSWFE EHEESDTERD FPLSKEYESC VRPRKCKPPL
KCNKAQICVD PNKGW
