TXF1A_SCOMU
ID TXF1A_SCOMU Reviewed; 76 AA.
AC A0A2L0ART2; A0A2R2JFU4; C0HKE0;
DT 20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT 25-APR-2018, sequence version 1.
DT 25-MAY-2022, entry version 14.
DE RecName: Full=Mu-scoloptoxin(15)-Ssm1a {ECO:0000305};
DE Short=Mu-SLPTX(15)-Ssm1a {ECO:0000305};
DE AltName: Full=Potassium channel toxin SsTx {ECO:0000303|PubMed:29358396};
DE AltName: Full=Ssm spooky toxin {ECO:0000303|PubMed:29358396};
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 24-76, STRUCTURE BY NMR OF
RP 24-76, FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY, TOXIC DOSE,
RP DISULFIDE BONDS, AND MUTAGENESIS OF LYS-27; LYS-28; ASP-29; LYS-33; LYS-34;
RP ARG-35; LYS-36; LYS-40; GLU-42; LYS-45; ASP-55; GLU-56; ARG-58; GLU-61;
RP LYS-63 AND LYS-68.
RC TISSUE=Venom, and Venom gland;
RX PubMed=29358396; DOI=10.1073/pnas.1714760115;
RA Luo L., Li B., Wang S., Wu F., Wang X., Liang P., Ombati R., Chen J.,
RA Lu X., Cui J., Lu Q., Zhang L., Zhou M., Tian C., Yang S., Lai R.;
RT "Centipedes subdue giant prey by blocking KCNQ channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:1646-1651(2018).
CC -!- FUNCTION: Blocks voltage-gated potassium channels Kv7.4/KCNQ4
CC (IC(50)=2.5 uM), Kv7.1/KCNQ1 (IC(50)=2.8 uM), Kv7.2/KCNQ2 (IC(50)=2.7
CC uM) and Kv7.5/KCNQ5 (IC(50)=2.7 uM). Targets the pore domain, in
CC particular negatively charged residues 'Asp-266' and 'Asp-288', of
CC KCNQ4 and probably other KCNQ channel family members where these
CC residues are conserved. In vivo, shows vasoconstrictive activity
CC resulting in acute hypertension when injected intravenously in mice.
CC Also induces coronary vasospasms ultimately leading to heart failure.
CC Induces seizures when injected into the hippocampus of mice. Decreases
CC respiratory rate while increasing respiratory amplitude, probably by
CC triggering a contraction of the bronchial ring.
CC {ECO:0000269|PubMed:29358396}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:29358396}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:29358396}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to a
CC beta-sheet by disulfide bonds (CSalpha/beta). Since the toxin contains
CC only 2 disulfide bonds, it is called 2ds-CSalpha/beta.
CC {ECO:0000269|PubMed:29358396}.
CC -!- MASS SPECTROMETRY: Mass=6017.5; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:29358396};
CC -!- TOXIC DOSE: LD(50) is 0.85 mg/kg when injected intravenously in mice.
CC {ECO:0000269|PubMed:29358396}.
CC -!- MISCELLANEOUS: Does not inhibit channels TRPV1 and TRPV2, voltage-gated
CC potassium channels Kv2.1/KCNB1 and Kv4.1/KCND1, hERG, tetrodotoxin
CC (TTX)-sensitive and TTX-insensitive sodium channels in DRG neurons or
CC voltage-gated calcium channels in DRG neurons.
CC {ECO:0000269|PubMed:29358396}.
CC -!- SIMILARITY: Belongs to the scoloptoxin-15 family. {ECO:0000305}.
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DR EMBL; MG585384; AUW64492.1; -; mRNA.
DR PDB; 5X0S; NMR; -; A=24-76.
DR PDBsum; 5X0S; -.
DR AlphaFoldDB; A0A2L0ART2; -.
DR SMR; A0A2L0ART2; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:0044499; P:envenomation resulting in positive regulation of blood pressure in another organism; IDA:UniProtKB.
DR GO; GO:1903817; P:negative regulation of voltage-gated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IDA:UniProtKB.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Potassium channel impairing toxin; Secreted;
KW Signal; Toxin; Voltage-gated potassium channel impairing toxin.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:29358396"
FT CHAIN 24..76
FT /note="Mu-scoloptoxin(15)-Ssm1a"
FT /evidence="ECO:0000269|PubMed:29358396"
FT /id="PRO_0000444563"
FT REGION 33..36
FT /note="Important for inhibition of KCNQ4"
FT /evidence="ECO:0000269|PubMed:29358396"
FT SITE 27
FT /note="Important for inhibition of KCNQ4"
FT /evidence="ECO:0000269|PubMed:29358396"
FT SITE 68
FT /note="Important for inhibition of KCNQ4"
FT /evidence="ECO:0000269|PubMed:29358396"
FT DISULFID 43..69
FT /evidence="ECO:0000269|PubMed:29358396,
FT ECO:0007744|PDB:5X0S"
FT DISULFID 47..71
FT /evidence="ECO:0000269|PubMed:29358396,
FT ECO:0007744|PDB:5X0S"
FT MUTAGEN 27
FT /note="K->A: Reduced inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 28
FT /note="K->A: No effect on inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 29
FT /note="D->A: No effect on inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 33
FT /note="K->A: Reduced inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 34
FT /note="K->A: Reduced inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 35
FT /note="R->A: Severely reduced inhibition of KCNQ4
FT (IC(50)=104.7 uM)."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 35
FT /note="R->K: No effect on inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 36
FT /note="K->A: Severaly reduced inhibition of KCNQ4
FT (IC(50)=117.5 uM)."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 36
FT /note="K->R: No effect on inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 40
FT /note="K->A: No effect on inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 42
FT /note="E->A: No effect on inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 45
FT /note="K->A: No effect on inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 55
FT /note="D->A: No effect on inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 56
FT /note="E->A: No effect on inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 58
FT /note="R->A: No effect on inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 61
FT /note="E->A: No effect on inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 63
FT /note="K->A: No effect on inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 68
FT /note="K->A: Reduced inhibition of KCNQ4."
FT /evidence="ECO:0000269|PubMed:29358396"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:5X0S"
FT HELIX 41..49
FT /evidence="ECO:0007829|PDB:5X0S"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:5X0S"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:5X0S"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:5X0S"
SQ SEQUENCE 76 AA; 8568 MW; 92484A9A32ADECB2 CRC64;
MEKKIIFLVF LVALLALPGF ISTEVIKKDT PYKKRKFPYK SECLKACATS FTGGDESRIQ
EGKPGFFKCT CYFTTG
