CTXL_MESMA
ID CTXL_MESMA Reviewed; 59 AA.
AC Q9UAD0;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=Chlorotoxin-like BmK CT {ECO:0000303|PubMed:10673158, ECO:0000303|PubMed:17166663, ECO:0000303|PubMed:21424168};
DE Short=BmKCT {ECO:0000303|PubMed:10708793, ECO:0000303|PubMed:19906483};
DE AltName: Full=Bm-12 {ECO:0000303|PubMed:10673158};
DE AltName: Full=BmKCL1;
DE AltName: Full=BmKClTx3 {ECO:0000303|PubMed:24129506};
DE AltName: Full=BmKClTx4 {ECO:0000303|PubMed:24129506};
DE AltName: Full=CT neurotoxin {ECO:0000312|EMBL:AAD47373.1};
DE AltName: Full=Short-chain toxin KCT {ECO:0000312|EMBL:AAG01185.1};
DE AltName: Full=TXCL1 {ECO:0000312|EMBL:AAK61823.1};
DE Flags: Precursor;
OS Mesobuthus martensii (Manchurian scorpion) (Buthus martensii).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus.
OX NCBI_TaxID=34649;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=10708793; DOI=10.1016/s0041-0101(99)00212-3;
RA Zeng X.-C., Li W.-X., Zhu S.-Y., Peng F., Zhu Z.-H., Wu K.-L., Yiang F.-H.;
RT "Cloning and characterization of a cDNA sequence encoding the precursor of
RT a chlorotoxin-like peptide from the Chinese scorpion Buthus martensii
RT Karsch.";
RL Toxicon 38:1009-1014(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Henan;
RX PubMed=10673158; DOI=10.1016/s0041-0101(99)00181-6;
RA Wu J.J., Dai L., Lan Z.D., Chi C.W.;
RT "The gene cloning and sequencing of Bm-12, a chlorotoxin-like peptide from
RT the scorpion Buthus martensi Karsch.";
RL Toxicon 38:661-668(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Venom gland;
RA Zhu S.-Y., Li W.-X.;
RT "cDNA encoding a putative insect toxin from BmK.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC TISSUE=Muscle;
RX PubMed=24129506; DOI=10.1038/ncomms3602;
RA Cao Z., Yu Y., Wu Y., Hao P., Di Z., He Y., Chen Z., Yang W., Shen Z.,
RA He X., Sheng J., Xu X., Pan B., Feng J., Yang X., Hong W., Zhao W., Li Z.,
RA Huang K., Li T., Kong Y., Liu H., Jiang D., Zhang B., Hu J., Hu Y.,
RA Wang B., Dai J., Yuan B., Feng Y., Huang W., Xing X., Zhao G., Li X.,
RA Li Y., Li W.;
RT "The genome of Mesobuthus martensii reveals a unique adaptation model of
RT arthropods.";
RL Nat. Commun. 4:2602-2602(2013).
RN [5]
RP PROTEIN SEQUENCE OF 25-37, SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=22887697; DOI=10.1002/pmic.201200224;
RA Xu J., Zhang X., Guo Z., Yan J., Yu L., Li X., Xue X., Liang X.;
RT "Short-chain peptides identification of scorpion Buthus martensi Karsch
RT venom by employing high orthogonal 2D-HPLC system and tandem mass
RT spectrometry.";
RL Proteomics 12:3076-3084(2012).
RN [6]
RP FUNCTION, AND PHARMACEUTICAL.
RX PubMed=17166663; DOI=10.1016/j.neulet.2006.10.056;
RA Fu Y.J., Yin L.T., Liang A.H., Zhang C.F., Wang W., Chai B.F., Yang J.Y.,
RA Fan X.J.;
RT "Therapeutic potential of chlorotoxin-like neurotoxin from the Chinese
RT scorpion for human gliomas.";
RL Neurosci. Lett. 412:62-67(2007).
RN [7]
RP PHARMACEUTICAL.
RX PubMed=19906483; DOI=10.1016/j.canlet.2009.10.011;
RA Fan S., Sun Z., Jiang D., Dai C., Ma Y., Zhao Z., Liu H., Wu Y., Cao Z.,
RA Li W.;
RT "BmKCT toxin inhibits glioma proliferation and tumor metastasis.";
RL Cancer Lett. 291:158-166(2010).
RN [8]
RP FUNCTION, MUTAGENESIS OF 37-ARG-LYS-38; ARG-40; LYS-48 AND ARG-58, AND
RP SITES ARG-37; LYS-38 AND ARG-40.
RX PubMed=21424168; DOI=10.1007/s10529-011-0587-7;
RA Fu Y.J., An N., Chan K.G., Wu Y.B., Zheng S.H., Liang A.H.;
RT "A model of BmK CT in inhibiting glioma cell migration via matrix
RT metalloproteinase-2 from experimental and molecular dynamics simulation
RT study.";
RL Biotechnol. Lett. 33:1309-1317(2011).
CC -!- FUNCTION: Toxin with unknown function in healthy organisms. On glioma
CC cells, inhibits chloride currents in a voltage-dependent manner (when
CC tested on gliomas cells) (PubMed:17166663). Also interacts with MMP2
CC and significantly inhibits its catalytic activity (PubMed:21424168).
CC May be internalized with chloride channels (probably ClC-3/CLCN3) and
CC MMP2, thus inhibiting the chloride channels necessary for cell
CC shrinkage and tumor propagation. {ECO:0000269|PubMed:17166663,
CC ECO:0000269|PubMed:21424168}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22887697}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:22887697}.
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=3747.48; Method=Electrospray; Note=Monoisotopic
CC mass.; Evidence={ECO:0000269|PubMed:22887697};
CC -!- PHARMACEUTICAL: This protein could be exploited as a potential
CC therapeutic for glioma diagnosis and therapy, since it significantly
CC inhibits the proliferation and metastasis of glioma cells, and has
CC selective affinity to glioma cells.
CC -!- MISCELLANEOUS: Does not inhibit potassium and sodium currents.
CC {ECO:0000305|PubMed:17166663}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Chloride
CC channel inhibitor family. {ECO:0000255|PROSITE-ProRule:PRU00545}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF135821; AAG01185.1; -; mRNA.
DR EMBL; AF079059; AAD47373.1; -; Genomic_DNA.
DR EMBL; AF159976; AAK61823.1; -; mRNA.
DR EMBL; AF419252; AAN32699.1; -; Genomic_DNA.
DR AlphaFoldDB; Q9UAD0; -.
DR SMR; Q9UAD0; -.
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:0008191; F:metalloendopeptidase inhibitor 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;
KW Metalloenzyme inhibitor; Metalloprotease inhibitor; Pharmaceutical;
KW Protease inhibitor; Secreted; Signal; Toxin;
KW Voltage-gated chloride channel impairing toxin.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:22887697"
FT CHAIN 25..59
FT /note="Chlorotoxin-like BmK CT"
FT /evidence="ECO:0000305|PubMed:22887697"
FT /id="PRO_0000035315"
FT SITE 37
FT /note="Important for the binding to the catalytic site of
FT MMP2"
FT SITE 38
FT /note="Important for the binding to the catalytic site of
FT MMP2"
FT SITE 40
FT /note="Important for the binding to the catalytic site of
FT MMP2"
FT DISULFID 25..42
FT /evidence="ECO:0000250|UniProtKB:P15222,
FT ECO:0000255|PROSITE-ProRule:PRU00545"
FT DISULFID 28..49
FT /evidence="ECO:0000250|UniProtKB:P15222,
FT ECO:0000255|PROSITE-ProRule:PRU00545"
FT DISULFID 39..54
FT /evidence="ECO:0000250|UniProtKB:P15222,
FT ECO:0000255|PROSITE-ProRule:PRU00545"
FT DISULFID 43..56
FT /evidence="ECO:0000250|UniProtKB:P15222,
FT ECO:0000255|PROSITE-ProRule:PRU00545"
FT MUTAGEN 37..38
FT /note="RK->AA: Important increase in inhibition rates of
FT glioma cell migration. Important decrease of inhibition of
FT the catalytic activity of MMP2."
FT /evidence="ECO:0000269|PubMed:21424168"
FT MUTAGEN 40
FT /note="R->A: Important increase in inhibition rates of
FT glioma cell migration. Important decrease of inhibition of
FT the catalytic activity of MMP2."
FT /evidence="ECO:0000269|PubMed:21424168"
FT MUTAGEN 48
FT /note="K->A: No change in inhibition rates of glioma cell
FT migration. Weak decrease of inhibition of the catalytic
FT activity of MMP2."
FT /evidence="ECO:0000269|PubMed:21424168"
FT MUTAGEN 58
FT /note="R->A: No change in inhibition rates of glioma cell
FT migration. Weak decrease of inhibition of the catalytic
FT activity of MMP2."
FT /evidence="ECO:0000269|PubMed:21424168"
SQ SEQUENCE 59 AA; 6467 MW; C9FAABAFCB8E02EA CRC64;
MKFLYGIVFI ALFLTVMFAT QTDGCGPCFT TDANMARKCR ECCGGIGKCF GPQCLCNRI
