ID   SCX4_CENVT              Reviewed;          83 AA.
AC   F8UWP3;
DT   22-NOV-2017, integrated into UniProtKB/Swiss-Prot.
DT   22-NOV-2017, sequence version 2.
DT   03-AUG-2022, entry version 38.
DE   RecName: Full=Alpha-toxin CvIV4 {ECO:0000303|PubMed:21887265};
DE   Flags: Precursor;
OS   Centruroides vittatus (Striped bark scorpion).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Centruroides.
OX   NCBI_TaxID=120091;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 20-59, FUNCTION, BIOASSAY,
RP   SUBUNIT, AND MASS SPECTROMETRY.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=21887265; DOI=10.1371/journal.pone.0023520;
RA   Rowe A.H., Xiao Y., Scales J., Linse K.D., Rowe M.P., Cummins T.R.,
RA   Zakon H.H.;
RT   "Isolation and characterization of CvIV4: a pain inducing alpha-scorpion
RT   toxin.";
RL   PLoS ONE 6:E23520-E23520(2011).
CC   -!- FUNCTION: This toxin significantly slows the fast inactivation of
CC       Nav1.2/SCN2A (EC(50)=580 nM), Nav1.3/SCN3A (EC(50)=1310 nM),
CC       Nav1.4/SCN4A (EC(50)=530 nM), and Nav1.7/SCN9A (EC(50)=1340 nM). The
CC       toxin does not affect the peak amplitude of Nav1.7 currents. On all
CC       channels cited above, the toxin requires depolarizing potentials to
CC       slow channel inactivation. In addition, the toxin has no or very weak
CC       effects on the voltage-dependence of steady-state inactivation, and on
CC       voltage-dependence of activation. In vivo, it produces paw licking in
CC       mice equivalent to the effects of whole venom.
CC       {ECO:0000269|PubMed:21887265}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21887265}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:21887265}.
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=6904.2; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:21887265};
CC   -!- MISCELLANEOUS: Has a minimal effect on Nav1.5/SCN5A and no effect on
CC       Nav1.8/SCN10A and Nav1.9/SCN11A sodium channels.
CC       {ECO:0000269|PubMed:21887265}.
CC   -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC       Sodium channel inhibitor family.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AEI61921.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; JF938594; AEI61921.1; ALT_INIT; mRNA.
DR   AlphaFoldDB; F8UWP3; -.
DR   SMR; F8UWP3; -.
DR   TCDB; 8.B.1.1.6; the long (4c-c) scorpion toxin (l-st) superfamily.
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:0000255"
FT   CHAIN           20..83
FT                   /note="Alpha-toxin CvIV4"
FT                   /evidence="ECO:0000305|PubMed:21887265"
FT                   /id="PRO_0000442239"
FT   DOMAIN          21..79
FT                   /note="LCN-type CS-alpha/beta"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        31..78
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        35..55
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        41..61
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        45..63
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
SQ   SEQUENCE   83 AA;  9488 MW;  F84B483AE3726587 CRC64;
     MNYFILILVA ALLILDVNCK KDGYPVEHSG CKYTCWKNEY CDKVCKDLKG EGGYCYINLT
     CWCTGLPDNV PLKTNQRCNG KRK