TX41A_SCOMU
ID TX41A_SCOMU Reviewed; 68 AA.
AC A0A0N7CSQ4; A0A0R4I950;
DT 31-JAN-2018, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 2.
DT 25-MAY-2022, entry version 17.
DE RecName: Full=Tau-scoloptoxin(04)-Sm1b {ECO:0000305};
DE Short=Tau-SLPTX(04)-Sm1b {ECO:0000305};
DE AltName: Full=Toxin RhTx2 {ECO:0000303|PubMed:32097697};
DE Contains:
DE RecName: Full=Tau-scoloptoxin(04)-Sm1a {ECO:0000305};
DE Short=Tau-SLPTX(04)-Sm1a {ECO:0000305};
DE AltName: Full=Toxin RhTx {ECO:0000303|PubMed:26420335};
DE Flags: Precursor;
OS Scolopendra mutilans (Chinese red-headed centipede) (Scolopendra
OS subspinipes mutilans).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Myriapoda; Chilopoda;
OC Pleurostigmophora; Scolopendromorpha; Scolopendridae; Scolopendra.
OX NCBI_TaxID=2836329;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 41-67, FUNCTION, SYNTHESIS
RP OF 41-67, MUTAGENESIS OF ARG-55; ASP-60; LYS-61; GLN-62 AND GLU-67,
RP STRUCTURE BY NMR OF 41-67, DISULFIDE BOND, MASS SPECTROMETRY, SUBCELLULAR
RP LOCATION, AND BIOASSAY.
RC TISSUE=Venom, and Venom gland;
RX PubMed=26420335; DOI=10.1038/ncomms9297;
RA Yang S., Yang F., Wei N., Hong J., Li B., Luo L., Rong M.,
RA Yarov-Yarovoy V., Zheng J., Wang K., Lai R.;
RT "A pain-inducing centipede toxin targets the heat activation machinery of
RT nociceptor TRPV1.";
RL Nat. Commun. 6:8297-8297(2015).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 37-67, FUNCTION, SYNTHESIS
RP OF 41-67, SYNTHESIS OF 37-67, MASS SPECTROMETRY, DISULFIDE BONDS,
RP 3D-STRUCTURE MODELING, AND SUBCELLULAR LOCATION.
RX PubMed=32097697; DOI=10.1016/j.toxicon.2020.02.016;
RA Zhu A., Aierken A., Yao Z., Vu S., Tian Y., Zheng J., Yang S., Yang F.;
RT "A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion
RT channel.";
RL Toxicon 178:41-49(2020).
CC -!- FUNCTION: [Tau-scoloptoxin(04)-Sm1a]: Extremely potent agonist and
CC potentiator of TRPV1 (EC(50)=470-521.5 nM (mouse)) (PubMed:26420335,
CC PubMed:32097697). It strongly promotes the heat activation process by
CC downshifting the activation threshold temperature (PubMed:26420335). It
CC preferably binds to the activated channel and promotes its opening
CC (PubMed:26420335). Holding the channel closed by cooling prevents
CC binding of this toxin, leaving it ineffective (PubMed:26420335). The
CC toxin binds to the charge-rich outer pore region of the channel where
CC it directly interacts with the pore helix and turret, two adjacent
CC structural elements known to be critical for activation gating of TRPV1
CC (PubMed:26420335). In comparison with Sm1b, induces a TRPV1
CC desensitization with slower kinetics (20 seconds) (PubMed:32097697). In
CC vivo, induces pain in mice after intraplantar injection
CC (PubMed:26420335). {ECO:0000269|PubMed:26420335,
CC ECO:0000269|PubMed:32097697}.
CC -!- FUNCTION: [Tau-scoloptoxin(04)-Sm1b]: Potent agonist and probable
CC potentiator of TRPV1 (EC(50)=38.35 uM (mouse)) (PubMed:32097697). Also
CC binds to the outer pore region of TRPV1 (PubMed:32097697). In
CC comparison with Sm1a, induces a TRPV1 desensitization with faster
CC kinetics (2 seconds) and leads to a more complete TRPV1 desensitization
CC (PubMed:32097697). Desensitization is achieved by reducing both the
CC open probability and the single-channel conductance upon prolonged
CC exposure (PubMed:32097697). {ECO:0000269|PubMed:32097697}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26420335}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:26420335, ECO:0000305|PubMed:32097697}.
CC -!- DOMAIN: [Tau-scoloptoxin(04)-Sm1a]: Does not incorporate into the lipid
CC membrane. {ECO:0000269|PubMed:26420335}.
CC -!- MASS SPECTROMETRY: Mass=2967.3; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:26420335};
CC -!- MASS SPECTROMETRY: Mass=3458.8; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:32097697};
CC -!- MISCELLANEOUS: [Tau-scoloptoxin(04)-Sm1a]: Does not act on
CC mNav1.5/SCN5A, mNav1.7/SCN9A, tetrodotoxin-sensitive and -resistant
CC Nav, mKv1.1/KCNA1, mKv2.1/KCNB1, mKv4.1/KCND1, high voltage activated
CC Cav, low voltage activated Cav, TRPV2, TRPV3 and TRPV4.
CC {ECO:0000269|PubMed:26420335}.
CC -!- MISCELLANEOUS: [Tau-scoloptoxin(04)-Sm1b]: Has no or very weak activity
CC on TRPV2 and TRPV3. {ECO:0000269|PubMed:32097697}.
CC -!- SIMILARITY: Belongs to the scoloptoxin-04 family. {ECO:0000305}.
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DR EMBL; KM675476; AKN58847.1; -; mRNA.
DR PDB; 2MVA; NMR; -; A=41-67.
DR PDBsum; 2MVA; -.
DR AlphaFoldDB; A0A0N7CSQ4; -.
DR SMR; A0A0N7CSQ4; -.
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: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; Secreted; Signal; Toxin.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..36
FT /evidence="ECO:0000305|PubMed:32097697"
FT /id="PRO_0000442957"
FT PEPTIDE 37..67
FT /note="Tau-scoloptoxin(04)-Sm1b"
FT /evidence="ECO:0000269|PubMed:32097697"
FT /id="PRO_0000448930"
FT PEPTIDE 41..67
FT /note="Tau-scoloptoxin(04)-Sm1a"
FT /evidence="ECO:0000269|PubMed:26420335"
FT /id="PRO_5006011410"
FT REGION 55..67
FT /note="Highly charged C-terminal region, binds to TRPV1
FT channel"
FT /evidence="ECO:0000269|PubMed:26420335"
FT DISULFID 45..56
FT /evidence="ECO:0000269|PubMed:26420335,
FT ECO:0000269|PubMed:32097697, ECO:0000312|PDB:2MVA"
FT DISULFID 50..63
FT /evidence="ECO:0000269|PubMed:26420335,
FT ECO:0000269|PubMed:32097697, ECO:0000312|PDB:2MVA"
FT MUTAGEN 55
FT /note="R->A: 2-fold increase in potentiator activity."
FT /evidence="ECO:0000269|PubMed:26420335"
FT MUTAGEN 60
FT /note="D->A: 15-fold decrease in potentiator activity."
FT /evidence="ECO:0000269|PubMed:26420335"
FT MUTAGEN 61
FT /note="K->A: 2-fold decrease in potentiator activity."
FT /evidence="ECO:0000269|PubMed:26420335"
FT MUTAGEN 62
FT /note="Q->A: 7-fold decrease in potentiator activity."
FT /evidence="ECO:0000269|PubMed:26420335"
FT MUTAGEN 67
FT /note="E->A: 6-fold decrease in potentiator activity."
FT /evidence="ECO:0000269|PubMed:26420335"
FT CONFLICT 39
FT /note="E -> K (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:2MVA"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:2MVA"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:2MVA"
SQ SEQUENCE 68 AA; 7649 MW; 42C0FA69DE165FC7 CRC64;
MLKSFCILSV FMVLFLAKFP DLCSGEEISP LKIVVRNSEY LNNPCNGVTC PSGYRCSIVD
KQCIKKEK
