SCX2_CENSU
ID SCX2_CENSU Reviewed; 66 AA.
AC P08900;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Beta-mammal toxin Css2 {ECO:0000305};
DE AltName: Full=Css II {ECO:0000303|PubMed:10958995, ECO:0000303|PubMed:2435711};
DE Short=CssII {ECO:0000303|PubMed:17544584, ECO:0000303|PubMed:19524619, ECO:0000303|PubMed:21078353, ECO:0000303|PubMed:22251893};
OS Centruroides suffusus (Durango bark scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Centruroides.
OX NCBI_TaxID=6880;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, TOXIC DOSE, AMIDATION AT ASN-66, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=2435711; DOI=10.1016/s0021-9258(18)61214-1;
RA Martin M.-F., Garcia Y., Perez L.G., el Ayeb M., Kopeyan C., Bechis G.,
RA Jover E., Rochat H.;
RT "Purification and chemical and biological characterizations of seven toxins
RT from the Mexican scorpion, Centruroides suffusus suffusus.";
RL J. Biol. Chem. 262:4452-4459(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10958995; DOI=10.1016/s0196-9781(00)00206-0;
RA Johnson T.M., Quick M.W., Sakai T.T., Krishna N.R.;
RT "Expression of functional recombinant scorpion beta-neurotoxin Css II in E.
RT coli.";
RL Peptides 21:767-772(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Venom gland;
RX PubMed=17544584; DOI=10.1016/j.bbagen.2007.04.006;
RA Estrada G., Garcia B.I., Schiavon E., Ortiz E., Cestele S., Wanke E.,
RA Possani L.D., Corzo G.;
RT "Four disulfide-bridged scorpion beta neurotoxin CssII: heterologous
RT expression and proper folding in vitro.";
RL Biochim. Biophys. Acta 1770:1161-1168(2007).
RN [4]
RP PROTEIN SEQUENCE OF 1-15, MASS SPECTROMETRY, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=21329715; DOI=10.1016/j.toxicon.2011.02.006;
RA Espino-Solis G.P., Estrada G., Olamendi-Portugal T., Villegas E.,
RA Zamudio F., Cestele S., Possani L.D., Corzo G.;
RT "Isolation and molecular cloning of beta-neurotoxins from the venom of the
RT scorpion Centruroides suffusus suffusus.";
RL Toxicon 57:739-746(2011).
RN [5]
RP MUTAGENESIS OF GLU-15.
RX PubMed=19524619; DOI=10.1016/j.imlet.2009.06.001;
RA Hernandez-Salgado K., Estrada G., Olvera A., Coronas F.I., Possani L.D.,
RA Corzo G.;
RT "Heterologous expressed toxic and non-toxic peptide variants of toxin CssII
RT are capable to produce neutralizing antibodies against the venom of the
RT scorpion Centruroides suffusus suffusus.";
RL Immunol. Lett. 125:93-99(2009).
RN [6]
RP PHOSPHOLIPID-BINDING ACTIVITY.
RX PubMed=15632158; DOI=10.1074/jbc.m412552200;
RA Smith J.J., Alphy S., Seibert A.L., Blumenthal K.M.;
RT "Differential phospholipid binding by site 3 and site 4 toxins.
RT Implications for structural variability between voltage-sensitive sodium
RT channel domains.";
RL J. Biol. Chem. 280:11127-11133(2005).
RN [7]
RP MUTAGENESIS OF ASN-66 AND 64-THR--ASN-66, AND MASS SPECTROMETRY.
RX PubMed=21078353; DOI=10.1016/j.peptides.2010.11.001;
RA Estrada G., Restano-Cassulini R., Ortiz E., Possani L.D., Corzo G.;
RT "Addition of positive charges at the C-terminal peptide region of CssII, a
RT mammalian scorpion peptide toxin, improves its affinity for sodium channels
RT Nav1.6.";
RL Peptides 32:75-79(2011).
RN [8]
RP FUNCTION, AND 3D-STRUCTURE MODELING.
RC TISSUE=Venom;
RX PubMed=22200496; DOI=10.1016/j.toxicon.2011.12.003;
RA Schiavon E., Pedraza-Escalona M., Gurrola G.B., Olamendi-Portugal T.,
RA Corzo G., Wanke E., Possani L.D.;
RT "Negative-shift activation, current reduction and resurgent currents
RT induced by beta-toxins from Centruroides scorpions in sodium channels.";
RL Toxicon 59:283-293(2012).
RN [9]
RP NEUTRALIZATION BY ANTIBODY.
RX PubMed=30634620; DOI=10.3390/toxins11010032;
RA Riano-Umbarila L., Gomez-Ramirez I.V., Ledezma-Candanoza L.M.,
RA Olamendi-Portugal T., Rodriguez-Rodriguez E.R., Fernandez-Taboada G.,
RA Possani L.D., Becerril B.;
RT "Generation of a broadly cross-neutralizing antibody fragment against
RT several mexican scorpion venoms.";
RL Toxins 11:0-0(2019).
RN [10]
RP STRUCTURE BY NMR OF 1-66, FUNCTION, DISULFIDE BOND, AMIDATION AT ASN-66,
RP AND MASS SPECTROMETRY.
RX PubMed=22251893; DOI=10.1016/j.bbapap.2012.01.003;
RA Saucedo A.L., del Rio-Portilla F., Picco C., Estrada G., Prestipino G.,
RA Possani L.D., Delepierre M., Corzo G.;
RT "Solution structure of native and recombinant expressed toxin CssII from
RT the venom of the scorpion Centruroides suffusus suffusus, and their effects
RT on Nav1.5 sodium channels.";
RL Biochim. Biophys. Acta 1824:478-487(2012).
CC -!- FUNCTION: Beta toxin that binds site-4 of sodium channels (Nav) and
CC reduces peak current (observed on Nav1.6/SCN8A (IC(50)=307 nM)), shifts
CC the voltage of activation toward more negative potentials (observed on
CC Nav1.6, Nav1.1 (weak), Nav1.2 (weak), and Nav1.7 (weak)), and induces
CC resurgent currents at negative voltages following brief and strong
CC depolarizations (observed on Nav1.6, Nav1.1 (weak), and Nav1.7 (weak))
CC (PubMed:22200496). A reduction of peak current of Nav1.5/SCN7A has been
CC observed in another study (IC(50)=35-40 nM) (PubMed:22251893). This
CC toxin is only active on mammals (PubMed:17544584). It has been shown to
CC bind phospholipids (PubMed:15632158). {ECO:0000269|PubMed:15632158,
CC ECO:0000269|PubMed:17544584, ECO:0000269|PubMed:22200496,
CC ECO:0000269|PubMed:22251893, ECO:0000269|PubMed:2435711}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2435711}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:2435711}.
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 -!- PTM: C-terminal amidation increases its affinity for sodium channels.
CC {ECO:0000269|PubMed:2435711}.
CC -!- MASS SPECTROMETRY: Mass=7537.0; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:21078353, ECO:0000269|PubMed:22251893};
CC -!- MASS SPECTROMETRY: Mass=7537.6; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:21329715};
CC -!- TOXIC DOSE: LD(50) is 25 ug/kg by subcutaneous injection into mice and
CC 0.25 ug/kg by intracerebroventricular injection.
CC {ECO:0000269|PubMed:2435711}.
CC -!- TOXIC DOSE: LD(100) is 3 ug/kg by intracranial injection into mice.
CC {ECO:0000269|PubMed:21329715}.
CC -!- MISCELLANEOUS: Is the most abundant and deadly toxin from the venom of
CC C.s.suffusus. {ECO:0000269|PubMed:21329715}.
CC -!- MISCELLANEOUS: Does not show inhibition of peak current on Nav1.1,
CC Nav1.2, Nav1.3, Nav1.4, Nav1.5 and Nav1.7 (at 280 nM).
CC {ECO:0000269|PubMed:22200496}.
CC -!- MISCELLANEOUS: Is neutralized by the single-chain antibody fragment
CC 10FG2. {ECO:0000269|PubMed:30634620}.
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 PIR; A27406; A27406.
DR PDB; 2LI7; NMR; -; A=1-66.
DR PDB; 2LJM; NMR; -; A=1-66.
DR PDBsum; 2LI7; -.
DR PDBsum; 2LJM; -.
DR AlphaFoldDB; P08900; -.
DR BMRB; P08900; -.
DR SMR; P08900; -.
DR GO; GO:0005615; C:extracellular space; TAS:UniProtKB.
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 3D-structure; Amidation; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..66
FT /note="Beta-mammal toxin Css2"
FT /evidence="ECO:0000269|PubMed:2435711"
FT /id="PRO_0000066777"
FT DOMAIN 1..66
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT MOD_RES 66
FT /note="Asparagine amide"
FT /evidence="ECO:0000269|PubMed:22251893,
FT ECO:0000269|PubMed:2435711"
FT DISULFID 12..65
FT /evidence="ECO:0000269|PubMed:22251893,
FT ECO:0007744|PDB:2LI7, ECO:0007744|PDB:2LJM"
FT DISULFID 16..41
FT /evidence="ECO:0000269|PubMed:22251893,
FT ECO:0007744|PDB:2LI7, ECO:0007744|PDB:2LJM"
FT DISULFID 25..46
FT /evidence="ECO:0000269|PubMed:22251893,
FT ECO:0007744|PDB:2LI7, ECO:0007744|PDB:2LJM"
FT DISULFID 29..48
FT /evidence="ECO:0000269|PubMed:22251893,
FT ECO:0007744|PDB:2LI7, ECO:0007744|PDB:2LJM"
FT MUTAGEN 15
FT /note="E->R: Non-amidated peptide that is not toxic to mice
FT at concentrations up to 30 ug/20 g mouse body weight, when
FT injected intraperitoneally."
FT /evidence="ECO:0000269|PubMed:19524619"
FT MUTAGEN 64..66
FT /note="TCN->RCR: Non-amidated peptide that is as potent as
FT the amidated native peptide."
FT /evidence="ECO:0000269|PubMed:21078353"
FT MUTAGEN 64..66
FT /note="TCN->RCS: Non-amidated peptide that is almost
FT inactive."
FT /evidence="ECO:0000269|PubMed:21078353"
FT MUTAGEN 66
FT /note="N->H: Non-amidated peptide that is less potent than
FT the native peptide."
FT /evidence="ECO:0000269|PubMed:21078353"
FT MUTAGEN 66
FT /note="N->R: Non-amidated peptide that is less potent than
FT the native peptide."
FT /evidence="ECO:0000269|PubMed:21078353"
FT MUTAGEN 66
FT /note="N->S: Non-amidated peptide that is almost inactive."
FT /evidence="ECO:0000269|PubMed:21078353"
FT CONFLICT 27
FT /note="R -> G (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT STRAND 8..12
FT /evidence="ECO:0007829|PDB:2LI7"
FT STRAND 19..21
FT /evidence="ECO:0007829|PDB:2LI7"
FT HELIX 24..33
FT /evidence="ECO:0007829|PDB:2LI7"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:2LI7"
FT STRAND 43..50
FT /evidence="ECO:0007829|PDB:2LI7"
FT TURN 60..62
FT /evidence="ECO:0007829|PDB:2LI7"
SQ SEQUENCE 66 AA; 7547 MW; AEC8FE5FD071418C CRC64;
KEGYLVSKST GCKYECLKLG DNDYCLRECK QQYGKSSGGY CYAFACWCTH LYEQAVVWPL
PNKTCN
