KKX1U_UROMN
ID KKX1U_UROMN Reviewed; 68 AA.
AC C0HLG4;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2019, sequence version 1.
DT 25-MAY-2022, entry version 12.
DE RecName: Full=Wasabi receptor toxin {ECO:0000303|PubMed:31447178};
DE Short=WaTx {ECO:0000303|PubMed:31447178};
DE Flags: Precursor;
OS Urodacus manicatus (Black rock scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Scorpionoidea; Scorpionidae; Urodacinae; Urodacus.
OX NCBI_TaxID=1330407;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=24351712; DOI=10.3390/toxins5122456;
RA Sunagar K., Undheim E.A., Chan A.H., Koludarov I., Munoz-Gomez S.A.,
RA Antunes A., Fry B.G.;
RT "Evolution stings: the origin and diversification of scorpion toxin peptide
RT scaffolds.";
RL Toxins 5:2456-2487(2013).
RN [2]
RP PROTEIN SEQUENCE OF 36-68, STRUCTURE BY NMR OF 36-68, DISULFIDE BOND,
RP SUBCELLULAR LOCATION, MASS SPECTROMETRY, SUBUNIT, SYNTHESIS OF 36-68,
RP MUTAGENESIS OF GLN-39; GLN-40; LYS-42 AND ARG-67, FUNCTION, AND BIOASSAY.
RC TISSUE=Venom;
RX PubMed=31447178; DOI=10.1016/j.cell.2019.07.014;
RA Lin King J.V., Emrick J.J., Kelly M.J.S., Herzig V., King G.F.,
RA Medzihradszky K.F., Julius D.;
RT "A cell-penetrating scorpion toxin enables mode-specific modulation of
RT TRPA1 and pain.";
RL Cell 178:1362-1374(2019).
CC -!- FUNCTION: Cell-penetrating peptide (CPP) with defensive purpose that
CC induces pain by specifically activating mammalian sensory neuron TRPA1
CC channels. It non-covalently binds to the same region than other TRPA1
CC agonists (irritants), but acts via a distinct biochemical mechanism.
CC Its binding stabilizes the TRPA1 open state and diminishes calcium-
CC permeability. Consequently, it produces pain and pain hypersensitivity,
CC but fails to trigger efferent release of neuropeptides (CGRP) and
CC neurogenic inflammation typically produced by noxious electrophiles. Is
CC not active on voltage-gated potassium channels and other TRP channels.
CC {ECO:0000269|PubMed:31447178}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:31447178}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:31447178}. Host
CC cytoplasm {ECO:0000269|PubMed:31447178}. Note=Penetrates into cell via
CC passive diffusion and binds to the cytoplasmic side of TRPA1
CC (PubMed:31447178). {ECO:0000269|PubMed:31447178}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:31447178}.
CC -!- DOMAIN: Has the structural arrangement of two alpha-helices stabilized
CC by disulfide bonds (CSalpha/alpha 2(S-S)).
CC {ECO:0000269|PubMed:31447178}.
CC -!- MASS SPECTROMETRY: Mass=3854.5; Method=MALDI; Note=Monoisotopic mass.;
CC Evidence={ECO:0000269|PubMed:31447178};
CC -!- PHARMACEUTICAL: Could be used, as a first step, as a pharmacological
CC probe for dissecting TRPA1 function and its contribution to acute and
CC persistent pain. {ECO:0000305|PubMed:31447178}.
CC -!- MISCELLANEOUS: Has no effect on Kv1.2/KCNA2, Kv2.1/KCNB1, Kv3.1/KCNC1,
CC Kv4.3/KCND3, TRPM8, and TRPV1. {ECO:0000269|PubMed:31447178}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor kappa-KTx family. Kappa-KTx 1 subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=National Center for Biotechnology Information
CC (NCBI);
CC URL="https://trace.ncbi.nlm.nih.gov/Traces/sra/sra.cgi?run=SRR870663.19916.2";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Sting - Issue 219 of
CC November 2019;
CC URL="https://web.expasy.org/spotlight/back_issues/219/";
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DR PDB; 6OFA; NMR; -; A=36-68.
DR PDBsum; 6OFA; -.
DR AlphaFoldDB; C0HLG4; -.
DR BMRB; C0HLG4; -.
DR SMR; C0HLG4; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0099106; F:ion channel regulator activity; 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; Host cytoplasm;
KW Ion channel impairing toxin; Pharmaceutical; Secreted; Signal; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..35
FT /evidence="ECO:0000269|PubMed:31447178"
FT /id="PRO_0000448352"
FT CHAIN 36..68
FT /note="Wasabi receptor toxin"
FT /evidence="ECO:0000269|PubMed:31447178"
FT /id="PRO_0000448353"
FT DISULFID 44..62
FT /evidence="ECO:0000269|PubMed:31447178,
FT ECO:0007744|PDB:6OFA"
FT DISULFID 48..58
FT /evidence="ECO:0000269|PubMed:31447178,
FT ECO:0007744|PDB:6OFA"
FT MUTAGEN 39
FT /note="Q->A: No change in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:31447178"
FT MUTAGEN 40
FT /note="Q->A: No change in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:31447178"
FT MUTAGEN 42
FT /note="K->A: Decrease in ability penetrate membranes."
FT /evidence="ECO:0000269|PubMed:31447178"
FT MUTAGEN 67
FT /note="R->A: No change in cell-penetrating properties."
FT /evidence="ECO:0000269|PubMed:31447178"
FT CONFLICT 38..39
FT /note="PQ -> QD (in Ref. 1)"
FT /evidence="ECO:0000305"
FT HELIX 38..51
FT /evidence="ECO:0007829|PDB:6OFA"
FT HELIX 55..66
FT /evidence="ECO:0007829|PDB:6OFA"
SQ SEQUENCE 68 AA; 7978 MW; DB7476EB83758754 CRC64;
MKYFTLALTL LFLLLINPCK DMNFAWAESS EKVERASPQQ AKYCYEQCNV NKVPFDQCYQ
MCSPLERS
