SCX1_TITOB
ID SCX1_TITOB Reviewed; 86 AA.
AC P60214; A0A1E1WVS8; H1ZZH0;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 2.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=Beta-mammal/insect toxin To1 {ECO:0000303|PubMed:22355312, ECO:0000303|PubMed:30463697};
DE AltName: Full=NaTx12.1 {ECO:0000303|PubMed:22355312};
DE AltName: Full=Toxin Tc49b {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], AMIDATION AT LYS-84, 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:JAT91098.1}
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 21-84, FUNCTION, SUBCELLULAR LOCATION, MASS
RP SPECTROMETRY, AND BIOASSAY.
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.
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, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=30463697; DOI=10.1016/j.bbamem.2018.08.005;
RA Tibery D.V., Campos L.A., Mourao C.B.F., Peigneur S., Carvalho A.C.,
RA Tytgat J., Schwartz E.F.;
RT "Electrophysiological characterization of Tityus obscurus beta toxin 1
RT (To1) on Na+-channel isoforms.";
RL Biochim. Biophys. Acta 1861:142-150(2019).
CC -!- FUNCTION: Beta toxin that show multiple effects. It enhances the open
CC probability at more negative potentials of human Nav1.3/SCN3A and
CC Nav1.6/SCN8A, of the insect channel BgNaV1 and of arachnid VdNaV1
CC channel (PubMed:30463697). It promotes an important shift in slow
CC inactivation processes as a function of the prepulse voltage in human
CC Nav1.3/SCN3A and Nav1.6/SCN8A and a small shift in Nav1.1/SCN1A,
CC Nav1.2/SCN2A and Nav1.4/SCN4A (PubMed:30463697). Finally, it reduces
CC the peak of sodium currents in Nav1.3/SCN3A (80% inhibition at 70 nM of
CC toxin), Nav1.6/SCN8A (55.3%), Nav1.1/SCN1A (53.3%), Nav1.5/SCN5A
CC (46.7%), Nav1.2/SCN2A (42.7%) and Nav1.4/SCN4A (20%) voltage-gated
CC sodium channels (PubMed:30463697). It has also been shown to affect the
CC sodium current permeability of rat cerebellum granular cells in a
CC partially reversible manner (PubMed:11821128). In vivo, an
CC intraperitoneal injection (20 ug) into mice produces excitability,
CC respiratory problems, convulsions and death, within the first 30
CC minutes after injection (PubMed:11821128).
CC {ECO:0000269|PubMed:11821128, ECO:0000269|PubMed:30463697}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11821128,
CC ECO:0000269|PubMed:15025998}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:11821128}.
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=7405; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11821128};
CC -!- MASS SPECTROMETRY: Mass=7405.6; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:15025998};
CC -!- MASS SPECTROMETRY: Mass=7400.26; Method=MALDI; Note=Monoisotopic mass.;
CC Evidence={ECO:0000269|PubMed:30463697};
CC -!- MISCELLANEOUS: Does not modify the function of the Shaker B potassium
CC channels (PubMed:11821128). Does not reduce the peak of sodium currents
CC in Nav1.7/SCN9A, insect BgNav1 and arachnid VdNav1 (PubMed:30463697).
CC It does not promotes a shift in slow inactivation processes as a
CC function of the prepulse voltage in human Nav1.5/SCN5A and
CC Nav1.7/SCN9A, insect BgNav1 and arachnid VdNav1 (PubMed:30463697).
CC {ECO:0000269|PubMed:11821128, ECO:0000269|PubMed:30463697}.
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; HE585224; CCD31418.1; -; mRNA.
DR EMBL; GEMQ01000091; JAT91098.1; -; mRNA.
DR AlphaFoldDB; P60214; -.
DR SMR; P60214; -.
DR GO; GO:0005576; C:extracellular region; HDA:UniProtKB.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:0006952; P:defense response; IEA:InterPro.
DR GO; GO:0044489; P:negative regulation of voltage-gated sodium channel activity in another organism; IDA:UniProtKB.
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..84
FT /note="Beta-mammal/insect toxin To1"
FT /evidence="ECO:0000269|PubMed:11821128"
FT /id="PRO_0000066811"
FT DOMAIN 22..84
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT MOD_RES 84
FT /note="Lysine amide"
FT /evidence="ECO:0000269|PubMed:22355312"
FT DISULFID 32..83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 36..58
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 44..64
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 48..66
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT CONFLICT 51
FT /note="K -> R (in Ref. 2; JAT91098)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="K -> P (in Ref. 2; JAT91098)"
FT /evidence="ECO:0000305"
FT CONFLICT 78
FT /note="S -> R (in Ref. 2; JAT91098)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 86 AA; 10008 MW; 3386396FD66CB035 CRC64;
MTRFVLFISC FFLIDMIVEC KKEGYLVGND GCKYGCITRP HQYCVHECEL KKGTDGYCAY
WLACYCYNMP DWVKTWSSAT NKCKGK
