SCX4_TITOB
ID SCX4_TITOB Reviewed; 86 AA.
AC P60215; A0A1E1WVW0; H1ZZH3;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 2.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=Beta-toxin To4 {ECO:0000303|PubMed:22355312, ECO:0000303|PubMed:28735770};
DE AltName: Full=PT-beta* NaTx13.9;
DE AltName: Full=Toxin Tc54 {ECO:0000303|PubMed:11821128, ECO:0000303|PubMed:15025998};
DE Flags: Precursor;
OS Tityus obscurus (Amazonian scorpion) (Tityus cambridgei).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Tityus.
OX NCBI_TaxID=1221240;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROBABLE AMIDATION AT CYS-82, AND NOMENCLATURE.
RC TISSUE=Venom gland;
RX PubMed=22355312; DOI=10.1371/journal.pone.0030478;
RA Guerrero-Vargas J.A., Mourao C.B., Quintero-Hernandez V., Possani L.D.,
RA Schwartz E.F.;
RT "Identification and phylogenetic analysis of Tityus pachyurus and Tityus
RT obscurus novel putative Na+-channel scorpion toxins.";
RL PLoS ONE 7:E30478-E30478(2012).
RN [2] {ECO:0000312|EMBL:JAT91107.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Telson;
RX PubMed=29561852; DOI=10.1371/journal.pone.0193739;
RA de Oliveira U.C., Nishiyama M.Y. Jr., Dos Santos M.B.V.,
RA Santos-da-Silva A.P., Chalkidis H.M., Souza-Imberg A., Candido D.M.,
RA Yamanouye N., Dorce V.A.C., Junqueira-de-Azevedo I.L.M.;
RT "Proteomic endorsed transcriptomic profiles of venom glands from Tityus
RT obscurus and T. serrulatus scorpions.";
RL PLoS ONE 13:e0193739-e0193739(2018).
RN [3]
RP PROTEIN SEQUENCE OF 21-48, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=11821128; DOI=10.1016/s0041-0101(01)00252-5;
RA Batista C.V.F., Zamudio F.Z., Lucas S., Fox J.W., Frau A., Prestipino G.,
RA Possani L.D.;
RT "Scorpion toxins from Tityus cambridgei that affect Na(+)-channels.";
RL Toxicon 40:557-562(2002).
RN [4]
RP PROTEIN SEQUENCE OF 21-30, SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=15025998; DOI=10.1016/j.jchromb.2003.09.002;
RA Batista C.V.F., del Pozo L., Zamudio F.Z., Contreras S., Becerril B.,
RA Wanke E., Possani L.D.;
RT "Proteomics of the venom from the Amazonian scorpion Tityus cambridgei and
RT the role of prolines on mass spectrometry analysis of toxins.";
RL J. Chromatogr. B 803:55-66(2004).
RN [5]
RP FUNCTION, PROTEIN SEQUENCE OF 56-73, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=28735770; DOI=10.1016/j.peptides.2017.07.010;
RA Duque H.M., Mourao C.B.F., Tibery D.V., Barbosa E.A., Campos L.A.,
RA Schwartz E.F.;
RT "To4, the first Tityus obscurus beta-toxin fully electrophysiologically
RT characterized on human sodium channel isoforms.";
RL Peptides 95:106-115(2017).
CC -!- FUNCTION: Beta toxins bind voltage-independently at site-4 of sodium
CC channels (Nav) and shift the voltage of activation toward more negative
CC potentials thereby affecting sodium channel activation and promoting
CC spontaneous and repetitive firing. This toxin shows moderate inhibition
CC of Nav1.1/SCN1A, Nav1.2/SCN2A, and Nav1.4/SCN4A, and promotes a left
CC voltage shift on these channels. It exhibits similar potency on
CC Nav1.2/SCN2A and Nav1.4/SCN4A (40-50% peak current inhibition at 0.5
CC uM), and weaker inhibition on Nav1.2 (20-30% peak current inhibition at
CC 0.5 uM). {ECO:0000269|PubMed:28735770}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15025998}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:15025998}.
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=7259; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11821128};
CC -!- MASS SPECTROMETRY: Mass=7253.2; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:15025998};
CC -!- MASS SPECTROMETRY: Mass=7252.7; Method=MALDI; Note=Average mass.;
CC Evidence={ECO:0000269|PubMed:28735770};
CC -!- MISCELLANEOUS: Shows weak inhibition on Nav1.3/SCN3A, Nav1.5/SCN5A,
CC Nav1.8/SCN8A, and Nav1.7/SCN9A. {ECO:0000269|PubMed:28735770}.
CC -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC Sodium channel inhibitor family. Beta subfamily. {ECO:0000305}.
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DR EMBL; HE585227; CCD31421.1; -; mRNA.
DR EMBL; GEMQ01000082; JAT91107.1; -; mRNA.
DR AlphaFoldDB; P60215; -.
DR SMR; P60215; -.
DR GO; GO:0005576; C:extracellular region; HDA:UniProtKB.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; ISS:UniProtKB.
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; 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 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..20
FT /evidence="ECO:0000269|PubMed:11821128,
FT ECO:0000269|PubMed:15025998"
FT CHAIN 21..82
FT /note="Beta-toxin To4"
FT /evidence="ECO:0000305|PubMed:11821128,
FT ECO:0000305|PubMed:15025998, ECO:0000305|PubMed:22355312"
FT /id="PRO_5000851420"
FT DOMAIN 21..83
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT MOD_RES 82
FT /note="Cysteine amide"
FT /evidence="ECO:0000305|PubMed:22355312"
FT DISULFID 31..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 35..57
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 43..63
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 47..65
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT CONFLICT 42
FT /note="F -> G (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 86 AA; 10084 MW; 24AB220BA228B5B6 CRC64;
MTRFVLFISC FFLIGMIVEC KDGYLMEYGG CKMSCLMKKG TFCAEECTRM KGKDGYCYAW
LACYCYNMPD WVKIWNRATN KCGKRK
