ID   KA233_SCOTI             Reviewed;          57 AA.
AC   P0DP36;
DT   10-MAY-2017, integrated into UniProtKB/Swiss-Prot.
DT   10-MAY-2017, sequence version 1.
DT   25-MAY-2022, entry version 11.
DE   RecName: Full=Potassium channel toxin alpha-KTx 23.3 {ECO:0000303|PubMed:28077339};
DE   AltName: Full=Toxin St20 {ECO:0000303|PubMed:28077339};
DE   Flags: Precursor;
OS   Scorpiops tibetanus (Scorpion).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Iurida; Chactoidea; Euscorpiidae; Scorpiopinae; Scorpiopini;
OC   Scorpiops.
OX   NCBI_TaxID=500600;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], 3D-STRUCTURE MODELING, AND MUTAGENESIS OF
RP   LYS-45.
RC   TISSUE=Venom gland;
RX   PubMed=28077339; DOI=10.1016/j.toxicon.2017.01.005;
RA   Xiao M., Ding L., Yang W., Chai L., Sun Y., Yang X., Li D., Zhang H.,
RA   Li W., Cao Z., Wu Y., Li J., Li S., Chen Z.;
RT   "St20, a new venomous animal derived natural peptide with immunosuppressive
RT   and anti-inflammatory activities.";
RL   Toxicon 127:37-43(2017).
CC   -!- FUNCTION: This toxin shows both immunosuppressive and anti-inflammatory
CC       activities (PubMed:28077339). It has the potential to inhibit human T
CC       cell activation, since it reduces IL-2 secretion and the expression of
CC       T cell activation marker CD69 and acts as a anti-inflammatory agent,
CC       since it provokes the reduction of secretion of both IFN-gamma and TNF-
CC       alpha (PubMed:28077339). In vivo, the delayed-type hypersensitivity
CC       response in rat autoimmune disease model is ameliorated in the presence
CC       of this toxin (PubMed:28077339). Acts by blocking Kv1.3/KCNA3 potassium
CC       channels of T-lymphocytes (By similarity).
CC       {ECO:0000250|UniProtKB:P0DJ31, ECO:0000269|PubMed:28077339}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P0DJ31}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:28077339}.
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   -!- MISCELLANEOUS: Recombinant toxin does not cause hemolysis in human
CC       erythrocytes. {ECO:0000269|PubMed:28077339}.
CC   -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC       channel inhibitor family. Alpha-KTx 23 subfamily.
CC       {ECO:0000305|PubMed:28077339}.
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DR   AlphaFoldDB; P0DP36; -.
DR   SMR; P0DP36; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.30.10; -; 1.
DR   InterPro; IPR036574; Scorpion_toxin-like_sf.
DR   InterPro; IPR001947; Scorpion_toxinS_K_inh.
DR   Pfam; PF00451; Toxin_2; 1.
DR   PRINTS; PR00286; CHARYBDTOXIN.
DR   SUPFAM; SSF57095; SSF57095; 1.
PE   1: Evidence at protein level;
KW   Disulfide bond; Ion channel impairing toxin; Neurotoxin;
KW   Potassium channel impairing toxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..57
FT                   /note="Potassium channel toxin alpha-KTx 23.3"
FT                   /evidence="ECO:0000305|PubMed:28077339"
FT                   /id="PRO_0000439897"
FT   SITE            45
FT                   /note="Basic residue of the functional dyad"
FT   SITE            45
FT                   /note="Key residue for immunosuppressive and anti-
FT                   inflammatory activities"
FT                   /evidence="ECO:0000269|PubMed:28077339"
FT   SITE            54
FT                   /note="Aromatic residue of the functional dyad"
FT   DISULFID        26..46
FT                   /evidence="ECO:0000250|UniProtKB:P0DJ31"
FT   DISULFID        32..51
FT                   /evidence="ECO:0000250|UniProtKB:P0DJ31"
FT   DISULFID        36..53
FT                   /evidence="ECO:0000250|UniProtKB:P0DJ31"
FT   DISULFID        41..56
FT                   /evidence="ECO:0000250|UniProtKB:P0DJ31"
FT   MUTAGEN         45
FT                   /note="K->A: Complete loss of inhibition potency on human T
FT                   cells (IL-2, TNF-alpha and IFN-gamma secretion)."
FT                   /evidence="ECO:0000269|PubMed:28077339"
SQ   SEQUENCE   57 AA;  6175 MW;  C9391064ED2EEABE CRC64;
     MKMSIVIILL LFTCLIATNG ASGTKCSGSP ECVKFCRTKG CRNGKCMNRS CKCYLCS