SIX2_LEIQU
ID SIX2_LEIQU Reviewed; 82 AA.
AC P19855; Q8MVS6; Q8MVS7; Q8MVS8;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 24-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Beta-insect depressant toxin LqqIT2 {ECO:0000303|PubMed:15733572};
DE Short=Insect toxin 2;
DE Flags: Precursor;
OS Leiurus quinquestriatus quinquestriatus (Egyptian scorpion) (Deathstalker
OS scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Leiurus.
OX NCBI_TaxID=6885;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12467668; DOI=10.1016/s0041-0101(02)00242-8;
RA Zaki T.I., Maruniak J.E.;
RT "Three polymorphic genes encoding a depressant toxin from the Egyptian
RT scorpion Leiurus quinquestriatus quinquestriatus.";
RL Toxicon 41:109-113(2003).
RN [2]
RP PROTEIN SEQUENCE OF 22-82, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=2311768; DOI=10.1016/0014-5793(90)80607-k;
RA Kopeyan C., Mansuelle P., Sampieri F., Brando T., Bahraoui E.M., Rochat H.,
RA Granier C.;
RT "Primary structure of scorpion anti-insect toxins isolated from the venom
RT of Leiurus quinquestriatus quinquestriatus.";
RL FEBS Lett. 261:423-426(1990).
RN [3]
RP PROTEIN SEQUENCE OF 22-82, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=2029523; DOI=10.1021/bi00233a025;
RA Zlotkin E., Eitan M., Bindokas V.P., Adams M.E., Moyer M., Burkhart W.,
RA Fowler E.;
RT "Functional duality and structural uniqueness of depressant insect-
RT selective neurotoxins.";
RL Biochemistry 30:4814-4821(1991).
RN [4]
RP PROTEIN SEQUENCE OF 22-82, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=8431601; DOI=10.1002/arch.940220107;
RA Zlotkin E., Gurevitz M., Fowler E., Adams M.E.;
RT "Depressant insect selective neurotoxins from scorpion venom: chemistry,
RT action, and gene cloning.";
RL Arch. Insect Biochem. Physiol. 22:55-73(1993).
RN [5]
RP FUNCTION.
RA Zlotkin E., Fowler E., Eitan M., Moyer M., Adams M.E.;
RT "On the chemistry and action of the depressant insect toxins.";
RL Toxicon 28:170-170(1990).
RN [6]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=15733572; DOI=10.1016/j.toxicon.2004.12.010;
RA Bosmans F., Martin-Eauclaire M.-F., Tytgat J.;
RT "The depressant scorpion neurotoxin LqqIT2 selectively modulates the insect
RT voltage-gated sodium channel.";
RL Toxicon 45:501-507(2005).
RN [7]
RP FUNCTION.
RX PubMed=20619318; DOI=10.1016/j.neulet.2010.06.090;
RA Martin-Eauclaire M.F., Abbas N., Sauze N., Mercier L., Berge-Lefranc J.L.,
RA Condo J., Bougis P.E., Guieu R.;
RT "Involvement of endogenous opioid system in scorpion toxin-induced
RT antinociception in mice.";
RL Neurosci. Lett. 482:45-50(2010).
CC -!- FUNCTION: Depressant insect beta-toxins cause a transient contraction
CC paralysis followed by a slow flaccid paralysis. They bind voltage-
CC independently at site-4 of sodium channels and shift the voltage of
CC activation toward more negative potentials thereby affecting sodium
CC channel activation and promoting spontaneous and repetitive firing.
CC Aside from typical beta-toxin effects, this toxin also affects the
CC inactivation process and ion selectivity of the insect voltage-gated
CC sodium channel. This toxin is active only on insects (PubMed:15733572).
CC Is active on the insect voltage-gated sodium channel para
CC (PubMed:15733572). In vivo, when injected intraperitoneally, it
CC exhibits analgesic activity, increasing hot plate and tail flick
CC withdrawal latencies in a dose-dependent fashion (PubMed:20619318).
CC This phenomenon might be partly due to an inhibitory mechanism
CC activated by noxious stimuli (PubMed:20619318).
CC {ECO:0000269|PubMed:15733572, ECO:0000269|PubMed:20619318,
CC ECO:0000269|Ref.5}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2029523,
CC ECO:0000269|PubMed:2311768, ECO:0000269|PubMed:8431601}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:2311768}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to
CC antiparallel beta-sheets by disulfide bonds (CS-alpha/beta).
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: Does not affect the rat brain Nav1.2/SCN2A sodium
CC channel. {ECO:0000269|PubMed:15733572}.
CC -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC Sodium channel inhibitor family. Beta subfamily. {ECO:0000305}.
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DR EMBL; AF474983; AAM74027.1; -; mRNA.
DR EMBL; AF474984; AAM74028.1; -; mRNA.
DR EMBL; AF474985; AAM74029.1; -; mRNA.
DR PIR; B34123; B34123.
DR AlphaFoldDB; P19855; -.
DR SMR; P19855; -.
DR TCDB; 8.B.1.1.4; the long (4c-c) scorpion toxin (l-st) superfamily.
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 GO; GO:0006952; P:defense response; IEA:InterPro.
DR CDD; cd00107; Knot1; 1.
DR Gene3D; 3.30.30.10; -; 1.
DR InterPro; IPR044062; LCN-type_CS_alpha_beta_dom.
DR InterPro; IPR003614; Scorpion_toxin-like.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR InterPro; IPR018218; Scorpion_toxinL.
DR InterPro; IPR002061; Scorpion_toxinL/defensin.
DR Pfam; PF00537; Toxin_3; 1.
DR PRINTS; PR00285; SCORPNTOXIN.
DR SMART; SM00505; Knot1; 1.
DR SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS51863; LCN_CSAB; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:2029523,
FT ECO:0000269|PubMed:2311768, ECO:0000269|PubMed:8431601"
FT CHAIN 22..82
FT /note="Beta-insect depressant toxin LqqIT2"
FT /evidence="ECO:0000269|PubMed:2029523,
FT ECO:0000269|PubMed:2311768, ECO:0000269|PubMed:8431601"
FT /id="PRO_0000035196"
FT DOMAIN 22..82
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 31..81
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 35..56
FT /evidence="ECO:0000250|UniProtKB:P56637,
FT ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 42..63
FT /evidence="ECO:0000250|UniProtKB:P56637,
FT ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 46..65
FT /evidence="ECO:0000250|UniProtKB:P56637,
FT ECO:0000255|PROSITE-ProRule:PRU01210"
FT VARIANT 33
FT /note="L -> V"
FT VARIANT 43
FT /note="N -> D"
FT VARIANT 48
FT /note="S -> A"
FT VARIANT 71
FT /note="D -> E"
SQ SEQUENCE 82 AA; 9100 MW; F13D53B18CDECBF0 CRC64;
MKLLLLLIVS ASMLIESLVN ADGYIRKRDG CKLSCLFGNE GCNKECKSYG GSYGYCWTWG
LACWCEGLPD DKTWKSETNT CG
