DKTX_CYRSC
ID DKTX_CYRSC Reviewed; 79 AA.
AC P0CH43; D7QZ10;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 1.
DT 25-MAY-2022, entry version 34.
DE RecName: Full=Tau-theraphotoxin-Hs1a {ECO:0000305};
DE Short=Tau-TRTX-Hs1a {ECO:0000305};
DE AltName: Full=Double-knot toxin {ECO:0000303|PubMed:20510930};
DE Short=DkTx {ECO:0000303|PubMed:20510930};
OS Cyriopagopus schmidti (Chinese bird spider) (Haplopelma schmidti).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Cyriopagopus.
OX NCBI_TaxID=29017;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, DOMAIN, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=20510930; DOI=10.1016/j.cell.2010.03.052;
RA Bohlen C.J., Priel A., Zhou S., King D., Siemens J., Julius D.;
RT "A bivalent tarantula toxin activates the capsaicin receptor, TRPV1, by
RT targeting the outer pore domain.";
RL Cell 141:834-845(2010).
RN [2]
RP SUBUNIT.
RX PubMed=24305161; DOI=10.1038/nature12823;
RA Cao E., Liao M., Cheng Y., Julius D.;
RT "TRPV1 structures in distinct conformations reveal activation mechanisms.";
RL Nature 504:113-118(2013).
RN [3]
RP FUNCTION, STRUCTURE BY NMR OF 1-42 AND 43-75, MUTAGENESIS OF LEU-65, AND
RP LIPID-BINDING.
RX PubMed=26880553; DOI=10.7554/elife.11273;
RA Bae C., Anselmi C., Kalia J., Jara-Oseguera A., Schwieters C.D.,
RA Krepkiy D., Won Lee C., Kim E.H., Kim J.I., Faraldo-Gomez J.D.,
RA Swartz K.J.;
RT "Structural insights into the mechanism of activation of the TRPV1 channel
RT by a membrane-bound tarantula toxin.";
RL Elife 5:1-30(2016).
RN [4]
RP STRUCTURE BY ELECTRON MICROSCOPY (2.95 ANGSTROMS) OF 1-75, AND
RP LIPID-BINDING.
RX PubMed=27281200; DOI=10.1038/nature17964;
RA Gao Y., Cao E., Julius D., Cheng Y.;
RT "TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid
RT action.";
RL Nature 534:347-351(2016).
CC -!- FUNCTION: Selectively activates the heat-activated TRPV1 channel. It
CC binds to TRPV1 in an open state-dependent manner, trapping it there to
CC produce irreversible currents (PubMed:20510930, PubMed:26880553,
CC PubMed:27281200). It binds to the outer edge of the external pore of
CC TRPV1 in a counterclockwise configuration, using a limited protein-
CC protein interface and inserting hydrophobic residues into the bilayer
CC (PubMed:26880553, PubMed:27281200). It also partitions naturally into
CC membranes, with the two lobes exhibiting opposing energetics for
CC membrane partitioning (K1) and channel activation (K2)
CC (PubMed:26880553). In addition, the toxin disrupts a cluster of
CC hydrophobic residues behind the selectivity filter that are critical
CC for channel activation (PubMed:26880553). {ECO:0000269|PubMed:20510930,
CC ECO:0000269|PubMed:26880553, ECO:0000269|PubMed:27281200}.
CC -!- SUBUNIT: Interacts with TRPV1 (2 toxins (4 moieties) bind 1 channel
CC (homotetramer)). {ECO:0000269|PubMed:24305161}.
CC -!- INTERACTION:
CC P0CH43; O35433: Trpv1; Xeno; NbExp=2; IntAct=EBI-2793994, EBI-2794004;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20510930}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:20510930}.
CC -!- DOMAIN: The presence of 'disulfide through disulfide knots'
CC structurally defines this protein as a knottin. This toxin contains 2
CC 'disulfide through disulfide knots' that are separated by a short
CC linker. Bivalence accounts for irreversible toxin action.
CC {ECO:0000269|PubMed:20510930}.
CC -!- SIMILARITY: Belongs to the neurotoxin 23 family. Double-knot toxin
CC subfamily. {ECO:0000305}.
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DR EMBL; HM015001; ADE62145.1; -; mRNA.
DR PDB; 2N9Z; NMR; -; A=1-42.
DR PDB; 2NAJ; NMR; -; A=43-75.
DR PDB; 5IRX; EM; 2.95 A; E/F=1-75.
DR PDB; 6CUC; NMR; -; A=1-79.
DR PDB; 7L2M; EM; 3.84 A; E/F=1-75.
DR PDB; 7L2R; EM; 3.30 A; E/F=1-75.
DR PDB; 7L2T; EM; 3.08 A; E/F=1-75.
DR PDB; 7L2U; EM; 3.47 A; E/F=1-75.
DR PDBsum; 2N9Z; -.
DR PDBsum; 2NAJ; -.
DR PDBsum; 5IRX; -.
DR PDBsum; 6CUC; -.
DR PDBsum; 7L2M; -.
DR PDBsum; 7L2R; -.
DR PDBsum; 7L2T; -.
DR PDBsum; 7L2U; -.
DR AlphaFoldDB; P0CH43; -.
DR SMR; P0CH43; -.
DR DIP; DIP-62030N; -.
DR IntAct; P0CH43; 1.
DR ArachnoServer; AS001687; tau-theraphotoxin-Hs1a.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Lipid-binding; Repeat; Secreted;
KW Toxin.
FT CHAIN 1..79
FT /note="Tau-theraphotoxin-Hs1a"
FT /evidence="ECO:0000305|PubMed:20510930"
FT /id="PRO_0000398387"
FT REGION 1..35
FT /note="K1"
FT /evidence="ECO:0000305|PubMed:20510930"
FT REGION 36..42
FT /note="Linker"
FT /evidence="ECO:0000305|PubMed:20510930"
FT REGION 43..75
FT /note="K2"
FT /evidence="ECO:0000305|PubMed:20510930"
FT SITE 11
FT /note="Interacts with TRPV1 (reaches into the void formed
FT by S4, S6 and pore-helix)"
FT /evidence="ECO:0000269|PubMed:27281200"
FT SITE 25
FT /note="Important residue for activation of TRPV1"
FT /evidence="ECO:0000305|PubMed:26880553"
FT SITE 27
FT /note="Interacts with TRPV1 (reaches into the void formed
FT by S4, S6 and pore-helix)"
FT /evidence="ECO:0000269|PubMed:27281200"
FT SITE 53
FT /note="Interacts with TRPV1 (reaches into the void formed
FT by S4, S6 and pore-helix)"
FT /evidence="ECO:0000269|PubMed:27281200"
FT SITE 65
FT /note="Important residue for activation of TRPV1"
FT /evidence="ECO:0000269|PubMed:26880553"
FT SITE 67
FT /note="Interacts with TRPV1 (reaches into the void formed
FT by S4, S6 and pore-helix)"
FT /evidence="ECO:0000269|PubMed:27281200"
FT DISULFID 2..16
FT /evidence="ECO:0000269|PubMed:26880553,
FT ECO:0000269|PubMed:27281200, ECO:0000312|PDB:2N9Z,
FT ECO:0000312|PDB:5IRX"
FT DISULFID 9..23
FT /evidence="ECO:0000269|PubMed:26880553,
FT ECO:0000269|PubMed:27281200, ECO:0000312|PDB:2N9Z,
FT ECO:0000312|PDB:5IRX"
FT DISULFID 15..31
FT /evidence="ECO:0000269|PubMed:26880553,
FT ECO:0000269|PubMed:27281200, ECO:0000312|PDB:2N9Z,
FT ECO:0000312|PDB:5IRX"
FT DISULFID 44..58
FT /evidence="ECO:0000269|PubMed:26880553,
FT ECO:0000269|PubMed:27281200, ECO:0000312|PDB:2NAJ,
FT ECO:0000312|PDB:5IRX"
FT DISULFID 51..63
FT /evidence="ECO:0000269|PubMed:26880553,
FT ECO:0000269|PubMed:27281200, ECO:0000312|PDB:2NAJ,
FT ECO:0000312|PDB:5IRX"
FT DISULFID 57..71
FT /evidence="ECO:0000269|PubMed:26880553,
FT ECO:0000269|PubMed:27281200, ECO:0000312|PDB:2NAJ,
FT ECO:0000312|PDB:5IRX"
FT MUTAGEN 65
FT /note="L->A: Important decrease in activation of TRPV1 (in
FT K2 synthetic construct)."
FT /evidence="ECO:0000269|PubMed:26880553"
FT TURN 9..12
FT /evidence="ECO:0007829|PDB:5IRX"
FT TURN 18..20
FT /evidence="ECO:0007829|PDB:5IRX"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:5IRX"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:7L2T"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:5IRX"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:5IRX"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:2NAJ"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:5IRX"
SQ SEQUENCE 79 AA; 8983 MW; 8610FE914B72EAE3 CRC64;
DCAKEGEVCS WGKKCCDLDN FYCPMEFIPH CKKYKPYVPV TTNCAKEGEV CGWGSKCCHG
LDCPLAFIPY CEKYRGRND
