SCX8_ANDMA
ID SCX8_ANDMA Reviewed; 85 AA.
AC Q7YXD3; Q2YHM2;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Alpha-toxin Amm8 {ECO:0000305};
DE AltName: Full=Alpha-anatoxin Amm VIII {ECO:0000303|PubMed:20619318};
DE Short=Amm VIII {ECO:0000303|PubMed:12911331, ECO:0000303|PubMed:16533515, ECO:0000303|PubMed:18243273};
DE Short=AmmVIII {ECO:0000303|PubMed:20619318};
DE AltName: Full=Neurotoxin 8;
DE AltName: Full=P4;
DE Flags: Precursor;
OS Androctonus mauritanicus mauritanicus (Scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Androctonus.
OX NCBI_TaxID=6860;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 20-84, FUNCTION, MASS
RP SPECTROMETRY, TOXIC DOSE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Muscle;
RX PubMed=16533515; DOI=10.1016/j.toxicon.2006.01.005;
RA Alami M., Ceard B., Legros C., Bougis P.E., Martin-Eauclaire M.-F.;
RT "Genomic characterisation of the toxin Amm VIII from the scorpion
RT Androctonus mauretanicus mauretanicus.";
RL Toxicon 47:531-536(2006).
RN [3]
RP PARTIAL PROTEIN SEQUENCE, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=18243273; DOI=10.1016/j.toxicon.2007.12.012;
RA Oukkache N., Rosso J.-P., Alami M., Ghalim N., Saile R., Hassar M.,
RA Bougis P.E., Martin-Eauclaire M.-F.;
RT "New analysis of the toxic compounds from the Androctonus mauretanicus
RT mauretanicus scorpion venom.";
RL Toxicon 51:835-852(2008).
RN [4]
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).
RN [5]
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).
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 (PubMed:12911331). The toxin
CC principally slows the inactivation process of TTX-sensitive sodium
CC channels (PubMed:23685008). It discriminates neuronal versus muscular
CC sodium channel, as it is more potent on rat brain Nav1.2/SCN2A
CC (EC(50)=29 nM) than on rat skeletal muscle Nav1.4/SCN4A (EC(50)=416 nM)
CC (PubMed:12911331). It also shows a weak activity on Nav1.7/SCN9A
CC (EC(50)=1.76 uM) (PubMed:23685008). In vivo, the toxin produces pain
CC hypersensibility to mechanical and thermal stimuli.(PubMed:23685008).
CC It also exhibits potent analgesic activity (when injected
CC intraperitoneally), increasing hot plate and tail flick withdrawal
CC latencies in a dose-dependent fashion (PubMed:20619318). This
CC paradoxical analgesic action, is significantly suppressed by opioid
CC receptor antagonists, suggesting a pain-induced analgesia mechanism
CC that involves an endogenous opioid system (PubMed:20619318). This led
CC to hypothesis that pain relief induced by peripheral administration of
CC Amm VIII may result from sensitization of primary afferent neurons and
CC subsequent activation of an opioid-dependent noxious inhibitory control
CC (PubMed:20619318). {ECO:0000269|PubMed:12911331,
CC ECO:0000269|PubMed:20619318, ECO:0000269|PubMed:23685008}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12911331}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:12911331}.
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=7382.57; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:12911331};
CC -!- MASS SPECTROMETRY: Mass=7382; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:18243273};
CC -!- TOXIC DOSE: LD(50) is 11.25 ug/kg by intracerebroventricular injection
CC into mice but is not toxic (>1 mg/mouse) when injected subcutaneously.
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; AJ496808; CAD43222.1; -; mRNA.
DR EMBL; AM159181; CAJ43744.1; -; Genomic_DNA.
DR AlphaFoldDB; Q7YXD3; -.
DR SMR; Q7YXD3; -.
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..19
FT /evidence="ECO:0000269|PubMed:12911331"
FT CHAIN 20..84
FT /note="Alpha-toxin Amm8"
FT /evidence="ECO:0000269|PubMed:12911331"
FT /id="PRO_0000035232"
FT PROPEP 85
FT /note="Removed by a carboxypeptidase"
FT /id="PRO_0000035233"
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 DISULFID 35..55
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 41..65
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 45..67
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
SQ SEQUENCE 85 AA; 9654 MW; E8DC99F998D7DC8C CRC64;
MNYLVMISLA LLFMTGVESL KDGYIVNDIN CTYFCGRNAY CNELCIKLKG ESGYCQWASP
YGNSCYCYKL PDHVRTKGPG RCNDR
