SCL3_LEIHE
ID SCL3_LEIHE Reviewed; 67 AA.
AC P56678;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Alpha-like toxin Lqh3;
DE AltName: Full=Lqh III;
DE Short=LqhIII;
OS Leiurus hebraeus (Deathstalker scorpion) (Leiurus quinquestriatus
OS hebraeus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Leiurus.
OX NCBI_TaxID=6884;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, AMIDATION AT SER-67, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=9690781; DOI=10.1016/s0041-0101(98)00080-4;
RA Sautiere P., Cestele S., Kopeyan C., Martinage A., Drobecq H.,
RA Doljansky Y., Gordon D.;
RT "New toxins acting on sodium channels from the scorpion Leiurus
RT quinquestriatus hebraeus suggest a clue to mammalian vs insect
RT selectivity.";
RL Toxicon 36:1141-1154(1998).
RN [2]
RP FUNCTION.
RX PubMed=10678738; DOI=10.1007/s004249900181;
RA Chen H., Gordon D., Heinemann S.H.;
RT "Modulation of cloned skeletal muscle sodium channels by the scorpion
RT toxins Lqh II, Lqh III, and Lqh alphaIT.";
RL Pflugers Arch. 439:423-432(2000).
RN [3]
RP FUNCTION IN RAT BRAIN NEURONS.
RX PubMed=10516292; DOI=10.1523/jneurosci.19-20-08730.1999;
RA Gilles N., Blanchet C., Shichor I., Zaninetti M., Lotan I., Bertrand D.,
RA Gordon D.;
RT "A scorpion alpha-like toxin that is active on insects and mammals reveals
RT an unexpected specificity and distribution of sodium channel subtypes in
RT rat brain neurons.";
RL J. Neurosci. 19:8730-8739(1999).
RN [4]
RP FUNCTION ON HUMAN CARDIAC SODIUM CHANNELS.
RX PubMed=11382802; DOI=10.1085/jgp.117.6.505;
RA Chen H., Heinemann S.H.;
RT "Interaction of scorpion alpha-toxins with cardiac sodium channels: binding
RT properties and enhancement of slow inactivation.";
RL J. Gen. Physiol. 117:505-518(2001).
RN [5]
RP FUNCTION.
RX PubMed=17355257; DOI=10.1111/j.1742-4658.2007.05737.x;
RA Karbat I., Kahn R., Cohen L., Ilan N., Gilles N., Corzo G., Froy O.,
RA Gur M., Albrecht G., Heinemann S.H., Gordon D., Gurevitz M.;
RT "The unique pharmacology of the scorpion alpha-like toxin Lqh3 is
RT associated with its flexible C-tail.";
RL FEBS J. 274:1918-1931(2007).
RN [6]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=9917409; DOI=10.1006/jmbi.1998.2418;
RA Krimm I., Gilles N., Sautiere P., Stankiewicz M., Pelhate M., Gordon D.,
RA Lancelin J.-M.;
RT "NMR structures and activity of a novel alpha-like toxin from the scorpion
RT Leiurus quinquestriatus hebraeus.";
RL J. Mol. Biol. 285:1749-1763(1999).
RN [7]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=10987857; DOI=10.1046/j.1471-4159.2000.0751735.x;
RA Gilles N., Krimm I., Bouet F., Froy O., Gurevitz M., Lancelin J.-M.,
RA Gordon D.;
RT "Structural implications on the interaction of scorpion alpha-like toxins
RT with the sodium channel receptor site inferred from toxin iodination and
RT pH-dependent binding.";
RL J. Neurochem. 75:1735-1745(2000).
CC -!- FUNCTION: Alpha toxins bind voltage-independently at site-3 of sodium
CC channels (Nav) and inhibit the inactivation of the activated channels,
CC thereby blocking neuronal transmission. The dissociation is voltage-
CC dependent. This alpha-like toxin is highly toxic to insects and
CC competes with LqhaIT on binding to insect sodium channels. Differs from
CC classical anti-mammalian alpha-toxins as it inhibits sodium channel
CC inactivation in cell bodies of hippocampus brain neurons, on which the
CC anti-mammalian Lqh2 is inactive, and is unable to affect Nav1.2 in the
CC rat brain, on which Lqh2 is highly active. Moreover, its
CC pharmacological properties are unique in that its binding affinity for
CC insect channels drops >30-fold at pH 8.5 versus pH 6.5, and its rate of
CC association with receptor site-3 on both insect and mammalian sodium
CC channels is 4-15-fold slower compared with LqhaIT and Lqh2.
CC {ECO:0000269|PubMed:10516292, ECO:0000269|PubMed:10678738,
CC ECO:0000269|PubMed:11382802, ECO:0000269|PubMed:17355257,
CC ECO:0000269|PubMed:9690781}.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
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 -!- TOXIC DOSE: LD(50) is 50 mg/kg by intracerebroventricular injection
CC into mice. {ECO:0000269|PubMed:9690781}.
CC -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC Sodium channel inhibitor family. Alpha subfamily. {ECO:0000305}.
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DR PDB; 1BMR; NMR; -; A=1-67.
DR PDB; 1FH3; NMR; -; A=1-67.
DR PDB; 7K18; EM; 3.30 A; B=1-67.
DR PDBsum; 1BMR; -.
DR PDBsum; 1FH3; -.
DR PDBsum; 7K18; -.
DR AlphaFoldDB; P56678; -.
DR BMRB; P56678; -.
DR SMR; P56678; -.
DR TCDB; 8.B.1.1.8; the long (4c-c) scorpion toxin (l-st) superfamily.
DR EvolutionaryTrace; P56678; -.
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 3D-structure; Amidation; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..67
FT /note="Alpha-like toxin Lqh3"
FT /id="PRO_0000066784"
FT DOMAIN 2..66
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT MOD_RES 67
FT /note="Serine amide"
FT /evidence="ECO:0000269|PubMed:9690781"
FT DISULFID 12..65
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 16..37
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 23..47
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 27..49
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:7K18"
FT TURN 9..11
FT /evidence="ECO:0007829|PDB:7K18"
FT STRAND 18..20
FT /evidence="ECO:0007829|PDB:1BMR"
FT HELIX 24..30
FT /evidence="ECO:0007829|PDB:7K18"
FT STRAND 36..40
FT /evidence="ECO:0007829|PDB:7K18"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:7K18"
FT STRAND 44..52
FT /evidence="ECO:0007829|PDB:7K18"
SQ SEQUENCE 67 AA; 7057 MW; 19FE8EF96154328F CRC64;
VRDGYIAQPE NCVYHCFPGS SGCDTLCKEK GGTSGHCGFK VGHGLACWCN ALPDNVGIIV
EGEKCHS
