SCX4_ANDAU
ID SCX4_ANDAU Reviewed; 84 AA.
AC P45658; Q9BLM5;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 12-FEB-2003, sequence version 2.
DT 25-MAY-2022, entry version 90.
DE RecName: Full=Toxin Aah4 {ECO:0000305};
DE AltName: Full=AaH IV {ECO:0000303|PubMed:11311249, ECO:0000303|PubMed:1344902};
DE Short=AaHIV {ECO:0000303|PubMed:31668811};
DE AltName: Full=Neurotoxin 4 {ECO:0000305};
DE AltName: Full=Neurotoxin IV {ECO:0000303|PubMed:1344902};
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=11311249; DOI=10.1016/s0014-5793(01)02336-5;
RA Ceard B., Martin-Eauclaire M.-F., Bougis P.E.;
RT "Evidence for a position-specific deletion as an evolutionary link between
RT long- and short-chain scorpion toxins.";
RL FEBS Lett. 494:246-248(2001).
RN [2]
RP PROTEIN SEQUENCE OF 20-83, AND SUBCELLULAR LOCATION.
RC STRAIN=Hector; TISSUE=Venom;
RX PubMed=1344902; DOI=10.1002/nt.2620010112;
RA Mansuelle P., Martin M.-F., Rochat H., Granier C.;
RT "The amino acid sequence of toxin IV from the Androctonus australis
RT scorpion: differing effects of natural mutations in scorpion alpha-toxins
RT on their antigenic and toxic properties.";
RL Nat. Toxins 1:61-69(1992).
RN [3]
RP PARTIAL PROTEIN SEQUENCE, CHARACTERIZATION, AND TOXIC DOSE.
RX PubMed=3564061; DOI=10.1016/0041-0101(86)90139-x;
RA Martin M.F., Rochat H.;
RT "Large scale purification of toxins from the venom of the scorpion
RT Androctonus australis Hector.";
RL Toxicon 24:1131-1139(1986).
RN [4]
RP PROTEIN SEQUENCE OF 30-84, FUNCTION, MASS SPECTROMETRY, AND 3D-STRUCTURE
RP MODELING ALONE AND IN COMPLEX WITH NAV1.2/SCN2A; NAV1.6/SCN8A AND
RP NAV1.7/SNC9A.
RC TISSUE=Venom;
RX PubMed=31668811; DOI=10.1016/j.bbrc.2019.10.115;
RA BenAissa R., Othman H., Villard C., Peigneur S., Mlayah-Bellalouna S.,
RA Abdelkafi-Koubaa Z., Marrakchi N., Essafi-Benkhadir K., Tytgat J., Luis J.,
RA Srairi-Abid N.;
RT "AaHIV a sodium channel scorpion toxin inhibits the proliferation of DU145
RT prostate cancer cells.";
RL Biochem. Biophys. Res. Commun. 521:340-346(2020).
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. This toxin seems to
CC specifically act on Nav1.6/SCN8A sodium channel (PubMed:31668811). In
CC vitro, is active on DU145 prostate cancer cells proliferation
CC (IC(50)=15 uM). It shows low effect on the adhesion of DU145 cells to
CC fibronectin (at 15 uM) and is inactive on DU145 cells migration
CC (PubMed:31668811). {ECO:0000269|PubMed:31668811}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1344902}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:1344902}.
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 -!- MASS SPECTROMETRY: Mass=6882; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:31668811};
CC -!- TOXIC DOSE: LD(50) is 0.9 ug/kg by intracerebroventricular injection
CC into mice. {ECO:0000269|PubMed:3564061}.
CC -!- TOXIC DOSE: LD(50) is 0.75 ug/kg by intracerebroventricular injection
CC into mice. {ECO:0000269|PubMed:31668811}.
CC -!- MISCELLANEOUS: Does not show activity on Nav1.2/SCN2A, Nav1.4/SCN4A,
CC Nav1.5/SCN5A, Nav1.7/SCN9A, Nav1.8/SCN10A (when tested at 5 uM).
CC {ECO:0000269|PubMed:31668811}.
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; AJ308439; CAC37320.1; -; mRNA.
DR PIR; JC1321; JC1321.
DR AlphaFoldDB; P45658; -.
DR SMR; P45658; -.
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 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; IPR002061; Scorpion_toxinL/defensin.
DR Pfam; PF00537; Toxin_3; 1.
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..19
FT /evidence="ECO:0000269|PubMed:1344902"
FT CHAIN 20..83
FT /note="Toxin Aah4"
FT /evidence="ECO:0000269|PubMed:1344902"
FT /id="PRO_0000035223"
FT PROPEP 84
FT /note="Removed by a carboxypeptidase"
FT /id="PRO_0000035224"
FT DOMAIN 21..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..53
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 39..63
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 43..65
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
SQ SEQUENCE 84 AA; 9157 MW; 202EADE59F4018DA CRC64;
MNYLIMFSLA LLLVIGVESG RDGYIVDSKN CVYHCYPPCD GLCKKNGAKS GSCGFLVPSG
LACWCNDLPE NVPIKDPSDD CHKR
