SCX2_ANDAU
ID SCX2_ANDAU Reviewed; 85 AA.
AC P01484;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 3.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Alpha-mammal toxin AaH2 {ECO:0000303|PubMed:15133045};
DE AltName: Full=AaH II {ECO:0000303|PubMed:12911331, ECO:0000303|PubMed:15725394, ECO:0000303|PubMed:23685008, ECO:0000303|PubMed:2808423};
DE Short=AaHII;
DE AltName: Full=Neurotoxin II {ECO:0000303|PubMed:4342910};
DE Short=Toxin II {ECO:0000303|PubMed:15299886, ECO:0000303|PubMed:3174645, ECO:0000303|PubMed:4611766, ECO:0000303|PubMed:8145259};
DE Flags: Precursor;
OS Androctonus australis (Sahara scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Androctonus.
OX NCBI_TaxID=6858;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Hector; TISSUE=Venom gland;
RX PubMed=2808423; DOI=10.1016/s0021-9258(19)47295-5;
RA Bougis P.E., Rochat H., Smith L.A.;
RT "Precursors of Androctonus australis scorpion neurotoxins. Structures of
RT precursors, processing outcomes, and expression of a functional recombinant
RT toxin II.";
RL J. Biol. Chem. 264:19259-19265(1989).
RN [2]
RP PROTEIN SEQUENCE OF 20-83, AND SUBCELLULAR LOCATION.
RC STRAIN=Hector; TISSUE=Venom;
RX PubMed=4342910; DOI=10.1111/j.1432-1033.1972.tb01924.x;
RA Rochat H., Rochat C., Sampieri F., Miranda F., Lissitzky S.;
RT "The amino-acid sequence of neurotoxin II of Androctonus australis
RT hector.";
RL Eur. J. Biochem. 28:381-388(1972).
RN [3]
RP DISULFIDE BONDS.
RC STRAIN=Hector;
RX PubMed=4611766; DOI=10.1111/j.1432-1033.1974.tb03716.x;
RA Kopeyan C., Martinez G., Lissitzky S., Miranda F., Rochat H.;
RT "Disulfide bonds of toxin II of the scorpion Androctonus australis
RT hector.";
RL Eur. J. Biochem. 47:483-489(1974).
RN [4]
RP FUNCTION, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=12911331; DOI=10.1042/bj20030688;
RA Alami M., Vacher H., Bosmans F., Devaux C., Rosso J.-P., Bougis P.E.,
RA Tytgat J., Darbon H., Martin-Eauclaire M.-F.;
RT "Characterization of Amm VIII from Androctonus mauretanicus mauretanicus: a
RT new scorpion toxin that discriminates between neuronal and skeletal sodium
RT channels.";
RL Biochem. J. 375:551-560(2003).
RN [5]
RP MUTAGENESIS OF LYS-77 AND HIS-83, AMIDATION AT HIS-83, AND MASS
RP SPECTROMETRY.
RX PubMed=15725394; DOI=10.1016/j.bbagen.2005.01.008;
RA Legros C., Ceard B., Vacher H., Marchot P., Bougis P.E.,
RA Martin-Eauclaire M.-F.;
RT "Expression of the standard scorpion alpha-toxin AaH II and AaH II mutants
RT leading to the identification of some key bioactive elements.";
RL Biochim. Biophys. Acta 1723:91-99(2005).
RN [6]
RP FUNCTION.
RX PubMed=23685008; DOI=10.1016/j.pain.2013.03.037;
RA Abbas N., Gaudioso-Tyzra C., Bonnet C., Gabriac M., Amsalem M., Lonigro A.,
RA Padilla F., Crest M., Martin-Eauclaire M.F., Delmas P.;
RT "The scorpion toxin Amm VIII induces pain hypersensitivity through gain-of-
RT function of TTX-sensitive Na[+] channels.";
RL Pain 154:1204-1215(2013).
RN [7]
RP CRYSTALLIZATION.
RX PubMed=3174645; DOI=10.1073/pnas.85.20.7443;
RA Fontecilla-Camps J.-C., Habersetzer-Rochat C., Rochat H.;
RT "Orthorhombic crystals and three-dimensional structure of the potent toxin
RT II from the scorpion Androctonus australis Hector.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:7443-7447(1988).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS).
RC STRAIN=Hector;
RX PubMed=8145259; DOI=10.1006/jmbi.1994.1270;
RA Housset D., Habersetzer-Rochat C., Astier J.-P., Fontecilla-Camps J.-C.;
RT "Crystal structure of toxin II from the scorpion Androctonus australis
RT hector refined at 1.3-A resolution.";
RL J. Mol. Biol. 238:88-103(1994).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (0.96 ANGSTROMS).
RC STRAIN=Hector;
RX PubMed=15299886; DOI=10.1107/s0907444997005386;
RA Smith G.D., Blessing R.H., Ealick S.E., Fontecilla-Camps J.-C.,
RA Hauptman H.A., Housset D., Langs D.A., Miller R.;
RT "Ab initio structure determination and refinement of a scorpion protein
RT toxin.";
RL Acta Crystallogr. D 53:551-557(1997).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 20-83 (CHIMERA
RP AAH2/LQH-ALPHA-IT(27-29,36,75-81)), AND MUTAGENESIS OF 27-ASP--VAL-29;
RP GLY-36 AND 75-ARG--ARG-81.
RC STRAIN=Hector;
RX PubMed=15133045; DOI=10.1074/jbc.m402048200;
RA Karbat I., Frolow F., Froy O., Gilles N., Cohen L., Turkov M., Gordon D.,
RA Gurevitz M.;
RT "Molecular basis of the high insecticidal potency of scorpion alpha-
RT toxins.";
RL J. Biol. Chem. 279:31679-31686(2004).
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 toxin principally slows the
CC inactivation process of TTX-sensitive sodium channels
CC (PubMed:23685008). It is active on rat brain Nav1.2/SCN2A sodium
CC channel (EC(50)=2.6 nM) and on rat skeletal muscle Nav1.4/SCN4A sodium
CC channel (EC(50)=2.2 nM) (PubMed:12911331), as well as on human neuronal
CC Nav1.7/SCN9A (EC(50)=6.8 nM) (PubMed:23685008). This toxin is active
CC against mammals. In vivo, intraplantar injection into mice induces
CC spontaneous pain responses (PubMed:23685008).
CC {ECO:0000269|PubMed:12911331, ECO:0000269|PubMed:23685008}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:4342910}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:4342910}.
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 -!- PTM: The amidation of His-83 is not necessary for toxicity.
CC {ECO:0000269|PubMed:15725394}.
CC -!- MASS SPECTROMETRY: Mass=7243.20; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:15725394};
CC -!- TOXIC DOSE: LD(50) is 25 ng/kg by intracerebroventricular injection
CC into mice, and LD(50) is 11 ug/kg by subcutaneous injection.
CC {ECO:0000269|PubMed:12911331}.
CC -!- MISCELLANEOUS: Does not act on Nav1.8/SCN10A and Nav1.9/SCN11A when
CC tested on TTX-resistant sodium channels. {ECO:0000269|PubMed:23685008}.
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 EMBL; M27704; AAA29949.1; -; mRNA.
DR PIR; D34444; NTSR2A.
DR PDB; 1AHO; X-ray; 0.96 A; A=20-83.
DR PDB; 1PTX; X-ray; 1.30 A; A=20-83.
DR PDB; 1SEG; X-ray; 1.30 A; A=20-83.
DR PDB; 4AEI; X-ray; 2.30 A; A/B/C=20-83.
DR PDB; 6NT4; EM; 3.50 A; B/C=20-83.
DR PDBsum; 1AHO; -.
DR PDBsum; 1PTX; -.
DR PDBsum; 1SEG; -.
DR PDBsum; 4AEI; -.
DR PDBsum; 6NT4; -.
DR AlphaFoldDB; P01484; -.
DR SMR; P01484; -.
DR TCDB; 8.B.1.1.7; the long (4c-c) scorpion toxin (l-st) superfamily.
DR ABCD; P01484; 1 sequenced antibody.
DR EvolutionaryTrace; P01484; -.
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; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:4342910"
FT CHAIN 20..83
FT /note="Alpha-mammal toxin AaH2"
FT /evidence="ECO:0000269|PubMed:4342910"
FT /id="PRO_0000035220"
FT DOMAIN 21..83
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT MOD_RES 83
FT /note="Histidine amide"
FT /evidence="ECO:0000269|PubMed:15725394"
FT DISULFID 31..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210,
FT ECO:0000269|PubMed:4611766, ECO:0000269|PubMed:8145259,
FT ECO:0000312|PDB:1AHO, ECO:0000312|PDB:1PTX,
FT ECO:0000312|PDB:1SEG, ECO:0000312|PDB:4AEI"
FT DISULFID 35..55
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210,
FT ECO:0000269|PubMed:4611766, ECO:0000269|PubMed:8145259,
FT ECO:0000312|PDB:1AHO, ECO:0000312|PDB:1PTX,
FT ECO:0000312|PDB:1SEG, ECO:0000312|PDB:4AEI"
FT DISULFID 41..65
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210,
FT ECO:0000269|PubMed:4611766, ECO:0000269|PubMed:8145259,
FT ECO:0000312|PDB:1AHO, ECO:0000312|PDB:1PTX,
FT ECO:0000312|PDB:1SEG, ECO:0000312|PDB:4AEI"
FT DISULFID 45..67
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210,
FT ECO:0000269|PubMed:4611766, ECO:0000269|PubMed:8145259,
FT ECO:0000312|PDB:1AHO, ECO:0000312|PDB:1PTX,
FT ECO:0000312|PDB:1SEG, ECO:0000312|PDB:4AEI"
FT MUTAGEN 27..29
FT /note="DDV->KNY: In chimera Aah2/Lqh-alpha-IT(27-29,36,75-
FT 81); active on insects, but not on mammals."
FT /evidence="ECO:0000269|PubMed:15133045"
FT MUTAGEN 36
FT /note="G->F: In chimera Aah2/Lqh-alpha-IT(27-29,36,75-81);
FT active on insects, but not on mammals."
FT /evidence="ECO:0000269|PubMed:15133045"
FT MUTAGEN 75..81
FT /note="RTKGPGR->PIRVPGK: In chimera Aah2/Lqh-alpha-IT(27-
FT 29,36,75-81); active on insects, but not on mammals."
FT /evidence="ECO:0000269|PubMed:15133045"
FT MUTAGEN 77
FT /note="K->E,I,V: Loss of toxin toxicity; tested only
FT without C-terminal amidation."
FT /evidence="ECO:0000269|PubMed:15725394"
FT MUTAGEN 83
FT /note="H->HG: Little loss in toxicity; G-84 is not
FT amidated."
FT /evidence="ECO:0000269|PubMed:15725394"
FT STRAND 21..26
FT /evidence="ECO:0007829|PDB:1AHO"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:1SEG"
FT HELIX 38..47
FT /evidence="ECO:0007829|PDB:1AHO"
FT STRAND 51..59
FT /evidence="ECO:0007829|PDB:1AHO"
FT STRAND 62..70
FT /evidence="ECO:0007829|PDB:1AHO"
SQ SEQUENCE 85 AA; 9548 MW; 1740CC6B98363768 CRC64;
MNYLVMISLA LLFVTGVESV KDGYIVDDVN CTYFCGRNAY CNEECTKLKG ESGYCQWASP
YGNACYCYKL PDHVRTKGPG RCHGR
