TX2_CERMR
ID TX2_CERMR Reviewed; 33 AA.
AC P84508;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2005, sequence version 1.
DT 25-MAY-2022, entry version 58.
DE RecName: Full=Beta-theraphotoxin-Cm1b {ECO:0000305};
DE Short=Beta-TRTX-Cm1b {ECO:0000305};
DE AltName: Full=CcoTx-II {ECO:0000303|PubMed:29703751};
DE AltName: Full=Ceratotoxin-2 {ECO:0000303|PubMed:16267209};
DE Short=CcoTx2 {ECO:0000303|PubMed:16267209};
OS Ceratogyrus marshalli (Straighthorned baboon tarantula) (Ceratogyrus
OS cornuatus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Ceratogyrus.
OX NCBI_TaxID=316287;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, BIOASSAY, SUBCELLULAR LOCATION, MASS
RP SPECTROMETRY, AND AMIDATION AT LEU-33.
RC TISSUE=Venom;
RX PubMed=16267209; DOI=10.1124/mol.105.015941;
RA Bosmans F., Rash L., Zhu S., Diochot S., Lazdunski M., Escoubas P.,
RA Tytgat J.;
RT "Four novel tarantula toxins as selective modulators of voltage-gated
RT sodium channel subtypes.";
RL Mol. Pharmacol. 69:419-429(2006).
RN [2]
RP FUNCTION.
RX PubMed=28880874; DOI=10.1371/journal.pone.0182848;
RA Sousa S.R., Wingerd J.S., Brust A., Bladen C., Ragnarsson L., Herzig V.,
RA Deuis J.R., Dutertre S., Vetter I., Zamponi G.W., King G.F., Alewood P.F.,
RA Lewis R.J.;
RT "Discovery and mode of action of a novel analgesic beta-toxin from the
RT African spider Ceratogyrus darlingi.";
RL PLoS ONE 12:E0182848-E0182848(2017).
RN [3]
RP STRUCTURE BY NMR, FUNCTION, SYNTHESIS, AND DISULFIDE BOND.
RX PubMed=29703751; DOI=10.1074/jbc.ra118.002553;
RA Agwa A.J., Peigneur S., Chow C.Y., Lawrence N., Craik D.J., Tytgat J.,
RA King G.F., Henriques S.T., Schroeder C.I.;
RT "Gating modifier toxins isolated from spider venom: modulation of voltage-
RT gated sodium channels and the role of lipid membranes.";
RL J. Biol. Chem. 293:9041-9052(2018).
CC -!- FUNCTION: Inhibits several voltage-gated sodium channels and only one
CC voltage-gated calcium channel (Cav2.2/CACNA1B (IC(50)=1.1 uM) and
CC Nav1.2/SCN2A (IC(50)=3.7-80 nM), Nav1.3/SCN3A (IC(50)=88-5570 nM),
CC Nav1.1/SCN1A (IC(50)=170-407 nM), Nav1.7/SCN9A (IC(50)=95.5-230 nM),
CC Nav1.6/SCN6A (IC(50)=49.9-3990 nM), Nav1.4/SCN4A (IC(50)=113-400 nM or
CC >10 uM), Nav1.5/SCN5A (IC(50)=1524-1634 nM or >10 uM))
CC (PubMed:16267209, PubMed:28880874, PubMed:29703751). The toxin acts by
CC shifting the voltage dependence of channel activation to more
CC depolarized potentials and by blocking the inward component of the
CC sodium current (PubMed:16267209). It shows moderate affinity for lipid
CC bilayers without cholesterol and high affinity for lipid bilayers
CC containing cholesterol (PubMed:29703751). In vivo, this toxin causes
CC general ataxia, lack of response to stimuli, and semiparalysis
CC (PubMed:16267209). After a few minutes, the mice are unable to stand,
CC and breathing is reduced in rhythm and intensity (PubMed:16267209).
CC Symptoms gradually increase with progressive slowing of breathing and
CC flaccid paralysis; death occurred within 10 to 20 minutes post
CC injection (PubMed:16267209). Animals remain totally flaccid, and no
CC symptoms of excitatory neurotoxicity are observed (PubMed:16267209).
CC {ECO:0000269|PubMed:16267209, ECO:0000269|PubMed:28880874,
CC ECO:0000269|PubMed:29703751}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16267209}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:16267209}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000250|UniProtKB:P84507}.
CC -!- MASS SPECTROMETRY: Mass=4089.61; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:16267209};
CC -!- MISCELLANEOUS: Does not inhibit Cav1.3 and Cav3.1 (PubMed:28880874).
CC Does not or only weakly inhibits Nav1.8/SCN10A (PubMed:16267209,
CC PubMed:28880874). {ECO:0000269|PubMed:28880874}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 04 (CcoTx1)
CC subfamily. {ECO:0000305}.
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DR PDB; 6BTV; NMR; -; A=1-33.
DR PDBsum; 6BTV; -.
DR AlphaFoldDB; P84508; -.
DR BMRB; P84508; -.
DR SMR; P84508; -.
DR ArachnoServer; AS000248; beta-theraphotoxin-Cm1b.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:0044489; P:negative regulation of voltage-gated sodium channel activity in another organism; IDA:UniProtKB.
DR InterPro; IPR011696; Huwentoxin-1.
DR InterPro; IPR013140; Huwentoxin_CS1.
DR Pfam; PF07740; Toxin_12; 1.
DR PROSITE; PS60021; HWTX_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Calcium channel impairing toxin;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Knottin; Neurotoxin; Secreted; Toxin;
KW Voltage-gated calcium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT PEPTIDE 1..33
FT /note="Beta-theraphotoxin-Cm1b"
FT /evidence="ECO:0000269|PubMed:16267209"
FT /id="PRO_0000045001"
FT MOD_RES 33
FT /note="Leucine amide"
FT /evidence="ECO:0000269|PubMed:16267209"
FT DISULFID 2..17
FT /evidence="ECO:0000269|PubMed:29703751,
FT ECO:0000312|PDB:6BTV"
FT DISULFID 9..22
FT /evidence="ECO:0000269|PubMed:29703751,
FT ECO:0000312|PDB:6BTV"
FT DISULFID 16..29
FT /evidence="ECO:0000269|PubMed:29703751,
FT ECO:0000312|PDB:6BTV"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:6BTV"
FT HELIX 11..13
FT /evidence="ECO:0007829|PDB:6BTV"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:6BTV"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:6BTV"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:6BTV"
SQ SEQUENCE 33 AA; 4100 MW; 2DFCD300E19FFF1A CRC64;
DCLGWFKSCD PKNDKCCKNY TCSRRDRWCK YYL
