CTXL3_HOTTA
ID CTXL3_HOTTA Reviewed; 60 AA.
AC P83400; Q8T0X5;
DT 13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 13-DEC-2002, sequence version 2.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=Neurotoxin BtITx3 {ECO:0000303|PubMed:12297317};
DE AltName: Full=Neurotoxin BTChl1 {ECO:0000312|EMBL:AAL87236.1};
DE Flags: Precursor;
OS Hottentotta tamulus (Eastern Indian scorpion) (Mesobuthus tamulus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus.
OX NCBI_TaxID=34647;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Telson;
RA Newton K.A., Armugam A., Strong P.N., Jeyaseelan K.;
RT "Insect toxin from Mesobuthus tamulus.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 25-59, FUNCTION, SUBCELLULAR LOCATION, TOXIC DOSE, MASS
RP SPECTROMETRY, AND BIOASSAY.
RC TISSUE=Venom;
RX PubMed=12297317; DOI=10.1016/s0014-5793(02)03326-4;
RA Dhawan R., Joseph S., Sethi A., Lala A.K.;
RT "Purification and characterization of a short insect toxin from the venom
RT of the scorpion Buthus tamulus.";
RL FEBS Lett. 528:261-266(2002).
RN [3]
RP FUNCTION, AND SYNTHESIS OF 25-59.
RX PubMed=29483648; DOI=10.1038/s41594-018-0033-9;
RA Correnti C.E., Gewe M.M., Mehlin C., Bandaranayake A.D., Johnsen W.A.,
RA Rupert P.B., Brusniak M.Y., Clarke M., Burke S.E., De Van Der Schueren W.,
RA Pilat K., Turnbaugh S.M., May D., Watson A., Chan M.K., Bahl C.D.,
RA Olson J.M., Strong R.K.;
RT "Screening, large-scale production and structure-based classification of
RT cystine-dense peptides.";
RL Nat. Struct. Mol. Biol. 25:270-278(2018).
CC -!- FUNCTION: Toxin with unknown function in healthy organisms. On glioma
CC cells, interacts with chloride channels (probably ClC-3/CLCN3) and MMP2
CC at the surface of glioma cells. This complex is then internalized via
CC caveolae, thus inhibiting the chloride channels necessary for cell
CC shrinkage and tumor propagation (By similarity). Has been shown to
CC weakly inhibit Kv1.1/KCNA1, Kv1.2/KCNA2 and Kv1.3/KCNA3 voltage-gated
CC potassium channels (PubMed:29483648). In vivo, induces contraction,
CC severe paralysis and death in insect larva of Helicoverpa armigera
CC (PubMed:12297317). {ECO:0000250|UniProtKB:Q9UAD0,
CC ECO:0000269|PubMed:12297317}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12297317}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:12297317}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000250|UniProtKB:P15222}.
CC -!- MASS SPECTROMETRY: Mass=3796.5; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:12297317};
CC -!- TOXIC DOSE: LD(50) is 53.1 mg/kg when injected into the thoracic region
CC of insect larvae of H.armigera. {ECO:0000269|PubMed:12297317}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Chloride
CC channel inhibitor family. {ECO:0000255|PROSITE-ProRule:PRU00545}.
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DR EMBL; AF481880; AAL87236.1; -; mRNA.
DR AlphaFoldDB; P83400; -.
DR SMR; P83400; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0017081; F:chloride channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR InterPro; IPR007958; Scorpion_toxinS_Cl_inh.
DR Pfam; PF05294; Toxin_5; 1.
DR SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS51200; SHORT_SCORPION_CHLORIDE; 1.
PE 1: Evidence at protein level;
KW Chloride channel impairing toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin;
KW Potassium channel impairing toxin; Secreted; Signal; Toxin;
KW Voltage-gated chloride channel impairing toxin;
KW Voltage-gated potassium channel impairing toxin.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:12297317"
FT CHAIN 25..59
FT /note="Neurotoxin BtITx3"
FT /evidence="ECO:0000269|PubMed:12297317"
FT /id="PRO_0000035325"
FT PROPEP 60
FT /note="Removed by a carboxypeptidase"
FT /evidence="ECO:0000305"
FT /id="PRO_0000035326"
FT DISULFID 26..43
FT /evidence="ECO:0000250|UniProtKB:P15222,
FT ECO:0000255|PROSITE-ProRule:PRU00545"
FT DISULFID 29..50
FT /evidence="ECO:0000250|UniProtKB:P15222,
FT ECO:0000255|PROSITE-ProRule:PRU00545"
FT DISULFID 40..55
FT /evidence="ECO:0000250|UniProtKB:P15222,
FT ECO:0000255|PROSITE-ProRule:PRU00545"
FT DISULFID 44..57
FT /evidence="ECO:0000250|UniProtKB:P15222,
FT ECO:0000255|PROSITE-ProRule:PRU00545"
SQ SEQUENCE 60 AA; 6564 MW; C09D107FD2F2643F CRC64;
MKFLYGTILI AFFLTVMIAT HSEARCPPCF TTNPNMEADC RKCCGGRGYC ASYQCICPGG
