SCX2_CENNO
ID SCX2_CENNO Reviewed; 84 AA.
AC P01495; Q26461; Q6V4Y0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 3.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Beta-mammal toxin Cn2 {ECO:0000303|PubMed:10080898, ECO:0000303|PubMed:1371253, ECO:0000303|PubMed:8013663, ECO:0000303|PubMed:8585086};
DE Short=Toxin 2 {ECO:0000303|PubMed:10080898, ECO:0000303|PubMed:1371253, ECO:0000303|PubMed:8013663, ECO:0000303|PubMed:8585086};
DE AltName: Full=Toxin II.9.2.2 {ECO:0000303|Ref.4};
DE Flags: Precursor; Fragment;
OS Centruroides noxius (Mexican scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Centruroides.
OX NCBI_TaxID=6878;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND AMIDATION AT SER-82.
RC TISSUE=Venom, and Venom gland;
RX PubMed=8585086; DOI=10.1016/0041-0101(95)00058-t;
RA Vazquez A., Tapia J.V., Eliason W.K., Martin B.M., Lebreton F.,
RA Delepierre M., Possani L.D., Becerril B.;
RT "Cloning and characterization of the cDNAs encoding Na+ channel-specific
RT toxins 1 and 2 of the scorpion Centruroides noxius Hoffmann.";
RL Toxicon 33:1161-1170(1995).
RN [2]
RP PROTEIN SEQUENCE OF 17-82.
RC TISSUE=Venom;
RX PubMed=1371253; DOI=10.1111/j.1432-1033.1992.tb16635.x;
RA Zamudio F.Z., Saavedra R., Martin B.M., Gurrola G.B., Herion P.,
RA Possani L.D.;
RT "Amino acid sequence and immunological characterization with monoclonal
RT antibodies of two toxins from the venom of the scorpion Centruroides noxius
RT Hoffmann.";
RL Eur. J. Biochem. 204:281-292(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 17-81.
RA Zhu S.;
RT "Alignment of beta-toxin nucleotide sequences.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 17-46, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RA Martin B.M., Possani L.D., Dent M.A.R., Maelicke A.;
RT "N-terminal sequence of toxin II.9.2.2 from the venom of the Mexican
RT scorpion Centruroides noxius.";
RL Toxicon 20:74-74(1982).
RN [5]
RP DISULFIDE BONDS.
RX PubMed=8013663; DOI=10.1016/0014-5793(94)00507-9;
RA Gurrola G.B., Moreno-Hagelsieb G., Zamudio F.Z., Garcia M., Soberon X.,
RA Possani L.D.;
RT "The disulfide bridges of toxin 2 from the scorpion Centruroides noxius
RT Hoffmann and its three-dimensional structure calculated using the
RT coordinates of variant 3 from Centruroides sculpturatus.";
RL FEBS Lett. 347:59-62(1994).
RN [6]
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 [7]
RP STRUCTURE BY NMR OF 17-82, AND DISULFIDE BONDS.
RX PubMed=10080898; DOI=10.1006/jmbi.1999.2611;
RA Pintar A., Possani L.D., Delepierre M.;
RT "Solution structure of toxin 2 from Centruroides noxius Hoffmann, a beta-
RT scorpion neurotoxin acting on sodium channels.";
RL J. Mol. Biol. 287:359-367(1999).
CC -!- FUNCTION: Mammal beta-toxins bind voltage-independently at site-4 of
CC sodium channels (Nav) and shift the activation voltage to more negative
CC potentials. This toxin is active against mammals.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.4}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|Ref.4}.
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 -!- TOXIC DOSE: LD(50) is 20 ug/kg in mice.
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 EMBL; S81096; AAB36086.1; -; mRNA.
DR EMBL; AY351310; AAR08045.1; -; Genomic_DNA.
DR PIR; T10893; NTSR2N.
DR PDB; 1CN2; NMR; -; A=17-82.
DR PDB; 2YBR; X-ray; 2.55 A; C/F/I=17-82.
DR PDB; 2YC1; X-ray; 1.90 A; C/F=17-82.
DR PDB; 4V1D; X-ray; 3.10 A; C=17-82.
DR PDBsum; 1CN2; -.
DR PDBsum; 2YBR; -.
DR PDBsum; 2YC1; -.
DR PDBsum; 4V1D; -.
DR AlphaFoldDB; P01495; -.
DR BMRB; P01495; -.
DR SMR; P01495; -.
DR ABCD; P01495; 3 sequenced antibodies.
DR EvolutionaryTrace; P01495; -.
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 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..16
FT /evidence="ECO:0000269|PubMed:1371253, ECO:0000269|Ref.4"
FT CHAIN 17..82
FT /note="Beta-mammal toxin Cn2"
FT /id="PRO_0000035280"
FT DOMAIN 17..82
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT MOD_RES 82
FT /note="Serine amide"
FT /evidence="ECO:0000269|PubMed:8585086"
FT DISULFID 28..81
FT /evidence="ECO:0000269|PubMed:10080898,
FT ECO:0000269|PubMed:8013663, ECO:0007744|PDB:1CN2,
FT ECO:0007744|PDB:2YBR, ECO:0007744|PDB:2YC1,
FT ECO:0007744|PDB:4V1D"
FT DISULFID 32..57
FT /evidence="ECO:0000269|PubMed:10080898,
FT ECO:0000269|PubMed:8013663, ECO:0007744|PDB:1CN2,
FT ECO:0007744|PDB:2YBR, ECO:0007744|PDB:2YC1,
FT ECO:0007744|PDB:4V1D"
FT DISULFID 41..62
FT /evidence="ECO:0000269|PubMed:10080898,
FT ECO:0000269|PubMed:8013663, ECO:0007744|PDB:1CN2,
FT ECO:0007744|PDB:2YBR, ECO:0007744|PDB:2YC1,
FT ECO:0007744|PDB:4V1D"
FT DISULFID 45..64
FT /evidence="ECO:0000269|PubMed:10080898,
FT ECO:0000269|PubMed:8013663, ECO:0007744|PDB:1CN2,
FT ECO:0007744|PDB:2YBR, ECO:0007744|PDB:2YC1,
FT ECO:0007744|PDB:4V1D"
FT CONFLICT 24
FT /note="Missing (in Ref. 3; AAR08045)"
FT /evidence="ECO:0000305"
FT CONFLICT 49..50
FT /note="YG -> GY (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT NON_TER 1
FT TURN 24..26
FT /evidence="ECO:0007829|PDB:2YC1"
FT STRAND 33..37
FT /evidence="ECO:0007829|PDB:4V1D"
FT HELIX 39..49
FT /evidence="ECO:0007829|PDB:2YC1"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:2YC1"
FT STRAND 61..66
FT /evidence="ECO:0007829|PDB:2YC1"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:1CN2"
SQ SEQUENCE 84 AA; 9436 MW; 9784E065D37E2383 CRC64;
LLIITACLAL IGTVWAKEGY LVDKNTGCKY ECLKLGDNDY CLRECKQQYG KGAGGYCYAF
ACWCTHLYEQ AIVWPLPNKR CSGK
