SCX2_TITSE
ID SCX2_TITSE Reviewed; 84 AA.
AC P68410; A0A218QWV5; P23814;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 03-AUG-2022, sequence version 2.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=Alpha-mammal toxin Ts2 {ECO:0000303|PubMed:19689419};
DE AltName: Full=P-Mice-beta* NaTx5.1;
DE AltName: Full=Tityustoxin II;
DE Short=Toxin II;
DE Short=TsTX-II;
DE Short=Tst2;
DE AltName: Full=Toxin T1-IV;
DE AltName: Full=TsTX III-8 {ECO:0000303|PubMed:1993690};
DE AltName: Full=TsTX-III;
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:JAW06979.1, ECO:0000312|EMBL:JAW07016.1}
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:QPD99042.1}
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]
RP PROTEIN SEQUENCE OF 21-82, 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 [4]
RP PROTEIN SEQUENCE OF 21-82, FUNCTION, SUBCELLULAR LOCATION, AMIDATION AT
RP CYS-82, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=1344906; DOI=10.1002/nt.2620010211;
RA Mansuelle P., Martin-Eauclaire M.-F., Chavez-Olortegui C., de Lima M.E.,
RA Rochat H., Granier C.;
RT "The beta-type toxin Ts II from the scorpion Tityus serrulatus: amino acid
RT sequence determination and assessment of biological and antigenic
RT properties.";
RL Nat. Toxins 1:119-125(1992).
RN [5]
RP PROTEIN SEQUENCE OF 21-82, FUNCTION, SUBCELLULAR LOCATION, MASS
RP SPECTROMETRY, AND 3D-STRUCTURE MODELING.
RX PubMed=22356164; DOI=10.1111/j.1742-4658.2012.08545.x;
RA Cologna C.T., Peigneur S., Rustiguel J.K., Nonato M.C., Tytgat J.,
RA Arantes E.C.;
RT "Investigation of the relationship between the structure and function of
RT Ts2, a neurotoxin from Tityus serrulatus venom.";
RL FEBS J. 279:1495-1504(2012).
RN [6]
RP PROTEIN SEQUENCE OF 21-40, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom {ECO:0000303|PubMed:25199494};
RX PubMed=25199494; DOI=10.1016/j.toxicon.2014.08.064;
RA Pucca M.B., Amorim F.G., Cerni F.A., Bordon K.C.F., Cardoso I.A.,
RA Anjolette F.A., Arantes E.C.;
RT "Influence of post-starvation extraction time and prey-specific diet in
RT Tityus serrulatus scorpion venom composition and hyaluronidase activity.";
RL Toxicon 90:326-336(2014).
RN [7]
RP PROTEIN SEQUENCE OF 21-34, FUNCTION, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=1926167; DOI=10.1016/0041-0101(91)90058-y;
RA Sampaio S.V., Arantes E.C., Prado W.A., Riccioppo Neto F., Giglio J.R.;
RT "Further characterization of toxins T1IV (TsTX-III) and T2IV from Tityus
RT serrulatus scorpion venom.";
RL Toxicon 29:663-672(1991).
RN [8]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=21549737; DOI=10.1016/j.toxicon.2011.04.017;
RA Zoccal K.F., Bitencourt C.S., Secatto A., Sorgi C.A., Bordon K.C.,
RA Sampaio S.V., Arantes E.C., Faccioli L.H.;
RT "Tityus serrulatus venom and toxins Ts1, Ts2 and Ts6 induce macrophage
RT activation and production of immune mediators.";
RL Toxicon 57:1101-1108(2011).
RN [9]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=23085190; DOI=10.1016/j.toxicon.2012.10.002;
RA Zoccal K.F., Bitencourt C.S., Sorgi C.A., Bordon K.C., Sampaio S.V.,
RA Arantes E.C., Faccioli L.H.;
RT "Ts6 and Ts2 from Tityus serrulatus venom induce inflammation by mechanisms
RT dependent on lipid mediators and cytokine production.";
RL Toxicon 61:1-10(2013).
RN [10]
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 [11]
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).
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. This toxin acts on
CC Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.5/SCN5A, Nav1.6/SCN8A and Nav1.7/SCN9A
CC voltage-gated sodium channels, with the highest affinity for
CC Nav1.3/SCN3A, followed by Nav1.6/SCN8A and Nav1.7/SCN9A which are
CC affected almost equally. Interestingly, shows a significant shift of
CC the voltage dependence of activation for Nav1.3/SCN3A that is
CC characteristic of beta-toxins (PubMed:21549737). In addition, in
CC presence of LPS, this toxin inhibits the release of NO, IL-6 and TNF-
CC alpha in J774.1 cells (PubMed:21549737). Further, in the absence of
CC LPS, it stimulates the production of the anti-inflammatory cytokine IL-
CC 10 (PubMed:21549737, PubMed:23085190). This toxin is active on mammals.
CC {ECO:0000269|PubMed:1344906, ECO:0000269|PubMed:1926167,
CC ECO:0000269|PubMed:21549737, ECO:0000269|PubMed:22356164,
CC ECO:0000269|PubMed:23085190}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1344906,
CC ECO:0000269|PubMed:1926167, ECO:0000269|PubMed:1993690,
CC ECO:0000269|PubMed:22356164, ECO:0000269|PubMed:25199494}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:25199494}.
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=6998; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:22356164};
CC -!- TOXIC DOSE: LD(50) is 6 ng by intracerebroventricular injection into
CC mice (PubMed:1344906) and 12.9 +- 1.6 ug/kg when intracisternally
CC injected into mice (PubMed:1926167). {ECO:0000269|PubMed:1344906,
CC ECO:0000269|PubMed:1926167}.
CC -!- MISCELLANEOUS: This toxin does not affect Nav1.4/SCN4A, Nav1.8/SCN10A
CC and DmNa1/para. {ECO:0000305|PubMed:22356164}.
CC -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC Sodium channel inhibitor family. Beta subfamily. {ECO:0000305}.
CC -!- CAUTION: This toxin is functionally similar to alpha toxins and
CC structurally similar to beta toxins. {ECO:0000305}.
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DR EMBL; GEUW01000066; JAW06979.1; -; mRNA.
DR EMBL; GEUW01000029; JAW07016.1; -; mRNA.
DR EMBL; MT450706; QPD99042.1; -; mRNA.
DR PIR; B39510; B39510.
DR AlphaFoldDB; P68410; -.
DR SMR; P68410; -.
DR ABCD; P68410; 1 sequenced antibody.
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 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:0000255, ECO:0000305|PubMed:1344906,
FT ECO:0000305|PubMed:1926167, ECO:0000305|PubMed:1993690,
FT ECO:0000305|PubMed:22356164, ECO:0000305|PubMed:25199494"
FT CHAIN 21..82
FT /note="Alpha-mammal toxin Ts2"
FT /evidence="ECO:0000269|PubMed:1344906,
FT ECO:0000269|PubMed:1993690, ECO:0000269|PubMed:22356164"
FT /id="PRO_0000066824"
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:0000269|PubMed:1344906"
FT DISULFID 31..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 35..58
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"
SQ SEQUENCE 84 AA; 9349 MW; C2B66CDAA4D18E21 CRC64;
MKGFLLFISI LMMIGTIVVG KEGYAMDHEG CKFSCFIRPA GFCDGYCKTH LKASSGYCAW
PACYCYGVPD HIKVWDYATN KCGK
