SCX3_TITSE
ID SCX3_TITSE Reviewed; 86 AA.
AC P01496; A0A218QX01; P45659; P91788;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 03-AUG-2022, sequence version 5.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Alpha-mammal toxin Ts3 {ECO:0000303|PubMed:15051403, ECO:0000303|PubMed:15249424, ECO:0000303|PubMed:19689419, ECO:0000303|PubMed:22355312, ECO:0000303|PubMed:27244051};
DE AltName: Full=PT-Mice-alpha NaTx3.1 {ECO:0000303|PubMed:22355312};
DE AltName: Full=Tityustoxin IV {ECO:0000303|PubMed:8143874};
DE Short=Ts IV {ECO:0000303|PubMed:8143874};
DE Short=TsIV {ECO:0000305};
DE AltName: Full=Tityustoxin IV-5 {ECO:0000303|Ref.7};
DE Short=Toxin IV-5 {ECO:0000303|PubMed:1993690, ECO:0000303|PubMed:8711758, ECO:0000303|Ref.7};
DE Short=TsIV-5 {ECO:0000303|PubMed:2536799};
DE AltName: Full=Ts3(1-64) {ECO:0000303|PubMed:27244051};
DE Flags: Precursor;
OS Tityus serrulatus (Brazilian scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Tityus.
OX NCBI_TaxID=6887;
RN [1] {ECO:0000312|EMBL:JAW06971.1}
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 [2] {ECO:0000312|EMBL:QPD99043.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Telson;
RX PubMed=33181162; DOI=10.1016/j.toxicon.2020.11.001;
RA Kalapothakis Y., Miranda K., Pereira A.H., Witt A.S.A., Marani C.,
RA Martins A.P., Leal H.G., Campos-Junior E., Pimenta A.M.C., Borges A.,
RA Chavez-Olortegui C., Kalapothakis E.;
RT "Novel components of Tityus serrulatus venom: a transcriptomic approach.";
RL Toxicon 189:91-104(2021).
RN [3] {ECO:0000312|EMBL:AAB30413.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-86, PROTEIN SEQUENCE OF 20-49, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=8143874; DOI=10.1016/0014-5793(94)80496-6;
RA Martin-Eauclaire M.-F., Ceard B., Ribeiro A.M., Diniz C.R., Rochat H.,
RA Bougis P.E.;
RT "Biochemical, pharmacological and genomic characterisation of Ts IV, an
RT alpha-toxin from the venom of the South American scorpion Tityus
RT serrulatus.";
RL FEBS Lett. 342:181-184(1994).
RN [4] {ECO:0000312|EMBL:AAB37719.2}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 7-86.
RX PubMed=8711758; DOI=10.1016/0041-0101(95)00129-8;
RA Corona M., Zurita M., Possani L.D., Becerril B.;
RT "Cloning and characterization of the genomic region encoding toxin IV-5
RT from the scorpion Tityus serrulatus Lutz and Mello.";
RL Toxicon 34:251-256(1996).
RN [5]
RP PROTEIN SEQUENCE OF 20-81, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=1993690; DOI=10.1016/s0021-9258(18)49971-1;
RA Possani L.D., Martin B.M., Fletcher M.D., Fletcher P.L. Jr.;
RT "Discharge effect on pancreatic exocrine secretion produced by toxins
RT purified from Tityus serrulatus scorpion venom.";
RL J. Biol. Chem. 266:3178-3185(1991).
RN [6]
RP PROTEIN SEQUENCE OF 20-44, FUNCTION, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=12551849; DOI=10.1096/fj.02-0635fje;
RA Teixeira C.E., Ifa D.R., Corso G., Santagada V., Caliendo G., Antunes E.,
RA De Nucci G.;
RT "Sequence and structure-activity relationship of a scorpion venom toxin
RT with nitrergic activity in rabbit corpus cavernosum.";
RL FASEB J. 17:485-487(2003).
RN [7]
RP PROTEIN SEQUENCE OF 20-49.
RC TISSUE=Venom;
RA Possani L.D., Martin B.M., Mochca-Morales J., Svendsen I.;
RT "N-terminal sequence of toxin IV-5 from the venom of the scorpion Tytius
RT serrulatus.";
RL Toxicon 20:75-76(1982).
RN [8]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=2536799; DOI=10.1085/jgp.93.1.67;
RA Kirsch G.E., Skattebol A., Possani L.D., Brown A.M.;
RT "Modification of Na channel gating by an alpha scorpion toxin from Tityus
RT serrulatus.";
RL J. Gen. Physiol. 93:67-83(1989).
RN [9]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=15249424; DOI=10.1038/sj.bjp.0705793;
RA Campos F.V., Coronas F.I.V., Beirao P.S.L.;
RT "Voltage-dependent displacement of the scorpion toxin Ts3 from sodium
RT channels and its implication on the control of inactivation.";
RL Br. J. Pharmacol. 142:1115-1122(2004).
RN [10]
RP FUNCTION.
RX PubMed=15051403; DOI=10.1016/j.toxicon.2004.01.012;
RA Campos F.V., Moreira T.H., Beirao P.S.L., Cruz J.S.;
RT "Veratridine modifies the TTX-resistant Na+ channels in rat vagal afferent
RT neurons.";
RL Toxicon 43:401-406(2004).
RN [11]
RP NOMENCLATURE.
RX PubMed=19689419; DOI=10.2174/092986609788923329;
RA Cologna C.T., Marcussi S., Giglio J.R., Soares A.M., Arantes E.C.;
RT "Tityus serrulatus scorpion venom and toxins: an overview.";
RL Protein Pept. Lett. 16:920-932(2009).
RN [12]
RP NOMENCLATURE.
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 [13]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 20-83, FUNCTION, DISULFIDE BOND,
RP AND SYNTHESIS OF 20-81; 20-83; 20-85 AND 20-86.
RX PubMed=27244051; DOI=10.1002/anie.201603420;
RA Dang B., Kubota T., Mandal K., Correa A.M., Bezanilla F., Kent S.B.;
RT "Elucidation of the covalent and tertiary structures of biologically active
RT Ts3 toxin.";
RL Angew. Chem. Int. Ed. 55:8639-8642(2016).
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:2536799,
CC PubMed:15249424, PubMed:15051403). This synthetic toxin inhibits
CC inactivation of rat Nav1.4/SCN4A (when tested at 201 nM)
CC (PubMed:27244051). In addition, it has been shown to cause a persistent
CC sodium channel activation in nitrergic inhibitory fibers innervating
CC the rabbit corpus cavernosum, resulting in NO release and cavernosal
CC smooth muscle relaxation (PubMed:12551849). This toxin is active
CC against mammals (PubMed:2536799, PubMed:15249424, PubMed:15051403).
CC {ECO:0000269|PubMed:12551849, ECO:0000269|PubMed:15051403,
CC ECO:0000269|PubMed:15249424, ECO:0000269|PubMed:2536799,
CC ECO:0000269|PubMed:27244051}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1993690,
CC ECO:0000269|PubMed:8143874}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8143874}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to
CC antiparallel beta-sheets by disulfide bonds (CS-alpha/beta).
CC {ECO:0000269|PubMed:27244051}.
CC -!- MASS SPECTROMETRY: Mass=7427.66; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:12551849};
CC -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC Sodium channel inhibitor family. Alpha subfamily. {ECO:0000305}.
CC -!- CAUTION: The longest forms Tityustoxin V (also called Ts V and Ts3(1-
CC 66)) and Ts3(1-67) and the shortest form Tityustoxin III (also called
CC Ts III and Ts3(1-62)) show minimal effect on Nav1.4/SCN4A, suggesting
CC that the wild-type toxin corresponds to the amidated 64-residues long
CC peptide (PubMed:8143874, PubMed:27244051).
CC {ECO:0000269|PubMed:27244051, ECO:0000303|PubMed:8143874}.
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DR EMBL; GEUW01000074; JAW06971.1; -; mRNA.
DR EMBL; MT450707; QPD99043.1; -; mRNA.
DR EMBL; S69808; AAB30413.1; -; mRNA.
DR EMBL; S82286; AAB37719.2; -; Genomic_DNA.
DR PIR; S43674; NTSR4T.
DR PDB; 5CY0; X-ray; 1.93 A; A=20-83.
DR PDBsum; 5CY0; -.
DR AlphaFoldDB; P01496; -.
DR SMR; P01496; -.
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 3D-structure; 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..19
FT /evidence="ECO:0000255"
FT CHAIN 20..83
FT /note="Alpha-mammal toxin Ts3"
FT /evidence="ECO:0000305|PubMed:1993690,
FT ECO:0000305|PubMed:8143874, ECO:0000305|Ref.7"
FT /id="PRO_0000035299"
FT DOMAIN 21..82
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT MOD_RES 83
FT /note="Serine amide"
FT /evidence="ECO:0000250|UniProtKB:P01484"
FT DISULFID 31..81
FT /evidence="ECO:0000269|PubMed:27244051,
FT ECO:0000312|PDB:5CY0"
FT DISULFID 35..57
FT /evidence="ECO:0000269|PubMed:27244051,
FT ECO:0000312|PDB:5CY0"
FT DISULFID 43..64
FT /evidence="ECO:0000269|PubMed:27244051,
FT ECO:0000312|PDB:5CY0"
FT DISULFID 47..66
FT /evidence="ECO:0000269|PubMed:27244051,
FT ECO:0000312|PDB:5CY0"
FT CONFLICT 7
FT /note="L -> M (in Ref. 4; AAB37719)"
FT /evidence="ECO:0000305"
FT CONFLICT 76..79
FT /note="KTNG -> GST (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:5CY0"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:5CY0"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:5CY0"
FT HELIX 40..49
FT /evidence="ECO:0007829|PDB:5CY0"
FT STRAND 53..58
FT /evidence="ECO:0007829|PDB:5CY0"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:5CY0"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:5CY0"
SQ SEQUENCE 86 AA; 9807 MW; F2962D7109AB6179 CRC64;
MNYFILLVVV CLLTAGTEGK KDGYPVEYDN CAYICWNYDN AYCDKLCKDK KADSGYCYWV
HILCYCYGLP DSEPTKTNGK CKSGKK
