SCXA_LEIHE
ID SCXA_LEIHE Reviewed; 85 AA.
AC P17728;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Alpha-insect toxin LqhaIT;
DE AltName: Full=Lqh-alpha-IT;
DE Short=Alpha-IT;
DE Flags: Precursor;
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 NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=1801321; DOI=10.1016/0041-0101(91)90200-b;
RA Gurevitz M., Urbach D., Zlotkin E., Zilberberg N.;
RT "Nucleotide sequence and structure analysis of a cDNA encoding an alpha
RT insect toxin from the scorpion Leiurus quinquestriatus hebraeus.";
RL Toxicon 29:1270-1272(1991).
RN [2]
RP PROTEIN SEQUENCE OF 20-85.
RC TISSUE=Venom;
RX PubMed=2383565; DOI=10.1021/bi00477a009;
RA Eitan M., Fowler E., Herrmann R., Duval A., Pelhate M., Zlotkin E.;
RT "A scorpion venom neurotoxin paralytic to insects that affects sodium
RT current inactivation: purification, primary structure, and mode of
RT action.";
RL Biochemistry 29:5941-5947(1990).
RN [3]
RP MUTAGENESIS OF TYR-68; ALA-69 AND ASN-73, AND TOXIC DOSE.
RX PubMed=8756487; DOI=10.1021/bi9528309;
RA Zilberberg N., Gordon D., Pelhate M., Adams M.E., Norris T.M., Zlotkin E.,
RA Gurevitz M.;
RT "Functional expression and genetic alteration of an alpha scorpion
RT neurotoxin.";
RL Biochemistry 35:10215-10222(1996).
RN [4]
RP MUTAGENESIS OF LYS-27; 27-LYS--TYR-29; 27-LYS--GLU-34; TYR-29; GLU-34;
RP PHE-36; ARG-37; ASP-38; 37-ARG-ASP-38; 59-GLY-LYS-60; LYS-81 AND ARG-84.
RX PubMed=9169449; DOI=10.1074/jbc.272.23.14810;
RA Zilberberg N., Froy O., Loret E., Cestele S., Arad D., Gordon D.,
RA Gurevitz M.;
RT "Identification of structural elements of a scorpion alpha-neurotoxin
RT important for receptor site recognition.";
RL J. Biol. Chem. 272:14810-14816(1997).
RN [5]
RP ELECTROPHYSIOLOGICAL CHARACTERIZATION.
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16551474; DOI=10.1016/j.toxicon.2006.01.015;
RA Nascimento D.G., Rates B., Santos D.M., Verano-Braga T., Barbosa-Silva A.,
RA Dutra A.A.A., Biondi I., Martin-Eauclaire M.-F., De Lima M.E.,
RA Pimenta A.M.C.;
RT "Moving pieces in a taxonomic puzzle: venom 2D-LC/MS and data clustering
RT analyses to infer phylogenetic relationships in some scorpions from the
RT Buthidae family (Scorpiones).";
RL Toxicon 47:628-639(2006).
RN [7]
RP STRUCTURE BY NMR OF 20-82, AND DISULFIDE BONDS.
RX PubMed=9054546; DOI=10.1021/bi961497l;
RA Tugarinov V., Kustanovich I., Zilberberg N., Gurevitz M., Anglister J.;
RT "Solution structures of a highly insecticidal recombinant scorpion alpha-
RT toxin and a mutant with increased activity.";
RL Biochemistry 36:2414-2424(1997).
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 toxin is active on insects. It is also highly toxic to
CC crustaceans and has a measurable but low toxicity to mice.
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 250 ug/kg by subcutaneous injection to mice.
CC {ECO:0000269|PubMed:8756487}.
CC -!- MISCELLANEOUS: The binding sites for this contractive toxin differ from
CC those shared by the excitatory and depressant insect toxins.
CC -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC Sodium channel inhibitor family. Alpha subfamily. {ECO:0000305}.
CC -!- CAUTION: The mutagenesis studies described in PubMed:8756487 and
CC PubMed:9169449 are made with the sequence from PubMed:2383565 (see the
CC sequence conflict in position 83-85). {ECO:0000305}.
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DR PIR; A39306; A39306.
DR PDB; 1LQH; NMR; -; A=20-82.
DR PDB; 1LQI; NMR; -; A=20-82.
DR PDB; 2ASC; X-ray; 1.10 A; A=20-82.
DR PDB; 2ATB; X-ray; 1.60 A; A/B=20-82.
DR PDB; 2YEO; X-ray; 1.08 A; A=20-82.
DR PDBsum; 1LQH; -.
DR PDBsum; 1LQI; -.
DR PDBsum; 2ASC; -.
DR PDBsum; 2ATB; -.
DR PDBsum; 2YEO; -.
DR AlphaFoldDB; P17728; -.
DR SMR; P17728; -.
DR EvolutionaryTrace; P17728; -.
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; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:2383565"
FT CHAIN 20..85
FT /note="Alpha-insect toxin LqhaIT"
FT /id="PRO_0000035296"
FT DOMAIN 21..83
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 31..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210,
FT ECO:0000269|PubMed:9054546"
FT DISULFID 35..55
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210,
FT ECO:0000269|PubMed:9054546"
FT DISULFID 41..65
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210,
FT ECO:0000269|PubMed:9054546"
FT DISULFID 45..67
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210,
FT ECO:0000269|PubMed:9054546"
FT MUTAGEN 27
FT /note="K->A: 74% loss of toxicity and 39.4-fold decrease in
FT affinity to cockroach neuronal receptor."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 27
FT /note="K->D: 99.4% loss of toxicity and 1611-fold decrease
FT in affinity to cockroach neuronal receptor. 95% loss of
FT toxicity and 71.4-fold decrease in affinity to cockroach
FT neuronal receptor; when associated with A-34. 99.6% loss of
FT toxicity and 21303-fold decrease in affinity to cockroach
FT neuronal receptor; when associated with D-28 and V-29."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 28
FT /note="N->D: 99.6% loss of toxicity and 21303-fold decrease
FT in affinity to cockroach neuronal receptor; when associated
FT with D-27 and V-29."
FT MUTAGEN 29
FT /note="Y->S: 90% loss of toxicity and 114.3-fold decrease
FT in affinity to cockroach neuronal receptor."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 29
FT /note="Y->V: 99.6% loss of toxicity and 21303-fold decrease
FT in affinity to cockroach neuronal receptor; when associated
FT with D-27 and D-28."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 29
FT /note="Y->W: 57% loss of toxicity and 3.7-fold decrease in
FT affinity to cockroach neuronal receptor."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 34
FT /note="E->A: 77% loss of toxicity and 0.6-fold decrease in
FT affinity to cockroach neuronal receptor; 95% loss of
FT toxicity and 71.4-fold decrease in affinity to cockroach
FT neuronal receptor; when associated with D-27."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 36
FT /note="F->G: 86% loss of toxicity and 160-fold decrease in
FT affinity to cockroach neuronal receptor."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 37
FT /note="R->A: 78% loss of toxicity and 231.4-fold decrease
FT in affinity to cockroach neuronal receptor."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 37
FT /note="R->K: 59% loss of toxicity and 0.46-fold decrease in
FT affinity to cockroach neuronal receptor; when associated
FT with N-38."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 38
FT /note="D->H: 75% loss of toxicity and 6-fold decrease in
FT affinity to cockroach neuronal receptor."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 38
FT /note="D->N: 15% increase in toxicity and 1.2-fold decrease
FT in affinity to cockroach neuronal receptor; 59% loss of
FT toxicity and 0.46-fold decrease in affinity to cockroach
FT neuronal receptor; when associated with K-37."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 59
FT /note="G->S: 36% loss of toxicity and 25.7-fold decrease in
FT affinity to cockroach neuronal receptor; when associated
FT with P-60."
FT MUTAGEN 60
FT /note="K->P: 36% loss of toxicity and 25.7-fold decrease in
FT affinity to cockroach neuronal receptor; when associated
FT with S-59."
FT MUTAGEN 68
FT /note="Y->I: 20% loss of toxicity to mice and 1.18-fold
FT decrease in affinity to locust synaptosomal membranes; when
FT associated with K-69. 540% loss of toxicity to mice and
FT 1.08-fold decrease in affinity to locust synaptosomal
FT membranes; when associated with K-69 and K-73."
FT /evidence="ECO:0000269|PubMed:8756487"
FT MUTAGEN 69
FT /note="A->K: 20% loss of toxicity to mice and 1.18-fold
FT decrease in affinity to locust synaptosomal membranes; when
FT associated with I-68. 540% loss of toxicity to mice and
FT 1.08-fold decrease in affinity to locust synaptosomal
FT membranes; when associated with I-68 and K-73."
FT /evidence="ECO:0000269|PubMed:8756487"
FT MUTAGEN 73
FT /note="N->K: 540% loss of toxicity to mice and 1.08-fold
FT decrease in affinity to locust synaptosomal membranes; when
FT associated with I-68 and K-69."
FT /evidence="ECO:0000269|PubMed:8756487"
FT MUTAGEN 81
FT /note="K->L: 81% loss of toxicity and 220-fold decrease in
FT affinity to cockroach neuronal receptor."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 84
FT /note="R->A: 47% decrease in toxicity and 54.3-fold
FT decrease in affinity to cockroach neuronal receptor."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 84
FT /note="R->D: 95% decrease in toxicity and 2394-fold
FT decrease in affinity to cockroach neuronal receptor."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 84
FT /note="R->H: 220% decrease in toxicity and 0.3-fold
FT decrease in affinity to cockroach neuronal receptor."
FT /evidence="ECO:0000269|PubMed:9169449"
FT MUTAGEN 84
FT /note="R->N: 6% increase in toxicity and 58.6-fold decrease
FT in affinity to cockroach neuronal receptor."
FT /evidence="ECO:0000269|PubMed:9169449"
FT CONFLICT 83..85
FT /note="HRK -> R (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 20..27
FT /evidence="ECO:0007829|PDB:2YEO"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:2YEO"
FT HELIX 38..47
FT /evidence="ECO:0007829|PDB:2YEO"
FT STRAND 51..59
FT /evidence="ECO:0007829|PDB:2YEO"
FT STRAND 62..71
FT /evidence="ECO:0007829|PDB:2YEO"
SQ SEQUENCE 85 AA; 9571 MW; 3338BED532D53FA7 CRC64;
MNHLVMISLA LLLLLGVESV RDAYIAKNYN CVYECFRDAY CNELCTKNGA SSGYCQWAGK
YGNACWCYAL PDNVPIRVPG KCHRK
