TX1_CERDA
ID TX1_CERDA Reviewed; 33 AA.
AC P0DL84;
DT 20-DEC-2017, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2017, sequence version 1.
DT 25-MAY-2022, entry version 10.
DE RecName: Full=Beta-theraphotoxin-Cd1a {ECO:0000303|PubMed:28880874};
DE Short=Beta-TRTX-Cd1a {ECO:0000303|PubMed:28880874};
OS Ceratogyrus darlingi (Rear horned baboon tarantula).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Ceratogyrus.
OX NCBI_TaxID=2051643;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, AMIDATION AT LEU-33, SYNTHESIS, TOXIC DOSE,
RP SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
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).
CC -!- FUNCTION: Potent inhibitor of hNav1.7/SCN9A (IC(50)=16 nM, tested in
CC patch-clamp), and modest inhibitor of Cav2.2/CACNA1B (IC(50)~3 uM on
CC rat and human channel) (PubMed:28880874). It seems also to be potent on
CC hNav1.1/SCN1A (IC(50)=2.18 uM), hNav1.2/SCN2A (IC(50)=0.13 uM),
CC hNav1.7/SCN9A (IC(50)=3.34 uM) and hNav1.8/SCN10A (IC(50)=6.92 uM)
CC (tested in fluorimetric assays, which shows results with lower activity
CC than results obtained by patch-clamp) (PubMed:28880874). This toxin
CC inhibits Cav2.2/CACNA1B by acting near the pore region, but without
CC overlapping the omega-conotoxin binding site (PubMed:28880874). It also
CC seems to interfere with inactivation of Cav2.2/CACNA1B with no apparent
CC effects on the activation gating of the channel (PubMed:28880874).
CC Conversely, at Nav1.7/SCN9A it acts as a typical gating modifier toxin,
CC interacting with one or more of the voltage sensor domains and changing
CC the gating properties of this channel (PubMed:28880874). In vivo, it
CC reversibly paralyzes sheep blowflies (PubMed:28880874). In addition,
CC low doses of this toxin (400 pmol) fully reverse Nav1.7/SCN9A-evoked
CC pain behaviors in mice (without side effects), demonstrating its
CC analgesic potential (PubMed:28880874). {ECO:0000269|PubMed:28880874}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28880874}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:28880874}.
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=4028.2; Method=MALDI; Note=Monoisotopic mass.;
CC Evidence={ECO:0000269|PubMed:28880874};
CC -!- TOXIC DOSE: PD(50) is 1318 +-58 pmol/g when injected into the ventro-
CC lateral thoracic region of adult sheep blowflies (L.cuprina).
CC Remarkably, all flies fully recovers from the initial paralytic effects
CC induced by this toxin at doses up to 8.17 nmol/g.
CC {ECO:0000269|PubMed:28880874}.
CC -!- MISCELLANEOUS: Has no effect on some calcium channels (Cav1.3/CACNA1D
CC and Cav3.1/CACNA1G) and some sodium channels (Nav1.3/SCN3A,
CC Nav1.4/SCN4A, Nav1.5/SCN5A, and Nav1.6/SCN8A) (IC(50)>30 uM for all
CC channels) (tested in fluorimetric assays) (PubMed:28880874).
CC {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 AlphaFoldDB; P0DL84; -.
DR SMR; P0DL84; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR011696; Huwentoxin-1.
DR InterPro; IPR013140; Huwentoxin_CS1.
DR Pfam; PF07740; Toxin_12; 1.
PE 1: Evidence at protein level;
KW Amidation; Calcium channel impairing toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin; Secreted;
KW Toxin; Voltage-gated calcium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..33
FT /note="Beta-theraphotoxin-Cd1a"
FT /evidence="ECO:0000269|PubMed:28880874"
FT /id="PRO_0000442774"
FT MOD_RES 33
FT /note="Leucine amide"
FT /evidence="ECO:0000269|PubMed:28880874"
FT DISULFID 2..17
FT /evidence="ECO:0000250|UniProtKB:P84507"
FT DISULFID 9..22
FT /evidence="ECO:0000250|UniProtKB:P84507"
FT DISULFID 16..29
FT /evidence="ECO:0000250|UniProtKB:P84507"
SQ SEQUENCE 33 AA; 4038 MW; 2DED2300E744FF1A CRC64;
DCLGWFKSCD PKNDKCCKNY SCSRRDRWCK YDL
