TX32A_SCOMU
ID TX32A_SCOMU Reviewed; 112 AA.
AC P0DL36; C0HJF5;
DT 19-FEB-2014, integrated into UniProtKB/Swiss-Prot.
DT 11-JUN-2014, sequence version 2.
DT 25-MAY-2022, entry version 27.
DE RecName: Full=Mu-scoloptoxin(03)-Ssm2a {ECO:0000303|PubMed:24082113};
DE Short=Mu-SLPTX(03)-Ssm2a {ECO:0000303|PubMed:24082113};
DE AltName: Full=Mu-scoloptoxin-Ssm6a {ECO:0000303|PubMed:24082113};
DE Short=Mu-SLPTX-Ssm6a {ECO:0000303|PubMed:24082113};
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 66-87, FUNCTION, BIOASSAY,
RP DISULFIDE BONDS, MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND NOMENCLATURE.
RC TISSUE=Venom, and Venom gland;
RX PubMed=24082113; DOI=10.1073/pnas.1306285110;
RA Yang S., Xiao Y., Kang D., Liu J., Li Y., Undheim E.A., Klint J.K.,
RA Rong M., Lai R., King G.F.;
RT "Discovery of a selective NaV1.7 inhibitor from centipede venom with
RT analgesic efficacy exceeding morphine in rodent pain models.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:17534-17539(2013).
RN [2]
RP FUNCTION.
RX PubMed=25658507; DOI=10.1021/jm501765v;
RA Murray J.K., Ligutti J., Liu D., Zou A., Poppe L., Li H., Andrews K.L.,
RA Moyer B.D., McDonough S.I., Favreau P., Stoecklin R., Miranda L.P.;
RT "Engineering potent and selective analogues of GpTx-1, a tarantula venom
RT peptide antagonist of the Na(V)1.7 sodium channel.";
RL J. Med. Chem. 58:2299-2314(2015).
RN [3]
RP STRUCTURE BY NMR OF 66-111, AND DISULFIDE BOND.
RX PubMed=26073605; DOI=10.1016/j.str.2015.05.003;
RA Undheim E.A., Grimm L.L., Low C.F., Morgenstern D., Herzig V.,
RA Zobel-Thropp P., Pineda S.S., Habib R., Dziemborowicz S., Fry B.G.,
RA Nicholson G.M., Binford G.J., Mobli M., King G.F.;
RT "Weaponization of a hormone: convergent recruitment of hyperglycemic
RT hormone into the venom of arthropod predators.";
RL Structure 23:1283-1292(2015).
CC -!- FUNCTION: Gating-modifier toxin that inhibits voltage-gated sodium
CC channel with a preference for hNav1.7/SCN9A (IC(50)=25.4 nM) over
CC hNav1.1/SCN1A (IC(50)=4.1 uM), hNav1.2/SCN2A (IC(50)=813 nM), and
CC hNav1.6/SCN8A (IC(50)=15.2 uM) (PubMed:24082113). Is an effective
CC analgesic in rodent pain models, since it is several-fold more
CC effective than morphine in a rodent model of formalin-induced pain and
CC is equipotent with morphine in its ability to reduce thermal and acid-
CC induced pain (PubMed:24082113). In addition, this peptide shows a high
CC level of resistance to proteases and a high thermal stability that may
CC be explained by its predominant composition of alpha-helices
CC (PubMed:24082113). {ECO:0000269|PubMed:24082113}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24082113}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:24082113}.
CC -!- DOMAIN: Is exclusively composed of 4 tightly packed alpha helices (no
CC beta strand is present). {ECO:0000269|PubMed:26073605}.
CC -!- MASS SPECTROMETRY: Mass=5318.41; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:24082113};
CC -!- MISCELLANEOUS: Does not show effects on sodium channels hNav1.3/SCN3A,
CC hNav1.4/SCN4A, hNav1.5/SCN5A, hNav1.8/SCN10A and potassium channel
CC hKv11.1/KCNH2 (PubMed:24082113). The synthetic peptide has been found
CC to be inactive against Nav1.7/SCN9A at concentrations up to 1 uM, in
CC contrast to the isolated natural peptide described in PubMed:24082113
CC (PubMed:25658507). Intraperitoneal injection of this toxin has no
CC effect on blood pressure, heart rate, or motor function (as judged by a
CC swim test) at doses up to 1-10 umol/kg (PubMed:24082113).
CC {ECO:0000269|PubMed:24082113, ECO:0000269|PubMed:25658507}.
CC -!- MISCELLANEOUS: Arose via modification of ancestral neuropeptide
CC hormones (ion transport peptide/crustacean hyperglycemic hormones
CC (ITP/CHH)). {ECO:0000305|PubMed:26073605}.
CC -!- SIMILARITY: Belongs to the scoloptoxin-03 family. {ECO:0000305}.
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DR PDB; 2MUN; NMR; -; A=66-111.
DR PDB; 2MZ4; NMR; -; A=66-111.
DR PDBsum; 2MUN; -.
DR PDBsum; 2MZ4; -.
DR AlphaFoldDB; P0DL36; -.
DR BMRB; P0DL36; -.
DR SMR; P0DL36; -.
DR TCDB; 8.B.26.1.4; the scorpion toxin, scoloptoxin (scoloptoxin) family.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0017080; F:sodium 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; Neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..65
FT /evidence="ECO:0000305|PubMed:24082113"
FT /id="PRO_0000425498"
FT PEPTIDE 66..111
FT /note="Mu-scoloptoxin(03)-Ssm2a"
FT /evidence="ECO:0000305|PubMed:24082113"
FT /id="PRO_0000425499"
FT DISULFID 70..97
FT /evidence="ECO:0000269|PubMed:24082113,
FT ECO:0000269|PubMed:26073605, ECO:0000312|PDB:2MUN,
FT ECO:0000312|PDB:2MZ4"
FT DISULFID 80..96
FT /evidence="ECO:0000269|PubMed:24082113,
FT ECO:0000269|PubMed:26073605, ECO:0000312|PDB:2MUN,
FT ECO:0000312|PDB:2MZ4"
FT DISULFID 83..106
FT /evidence="ECO:0000269|PubMed:24082113,
FT ECO:0000269|PubMed:26073605, ECO:0000312|PDB:2MUN,
FT ECO:0000312|PDB:2MZ4"
FT HELIX 69..72
FT /evidence="ECO:0007829|PDB:2MUN"
FT HELIX 74..86
FT /evidence="ECO:0007829|PDB:2MUN"
FT HELIX 92..96
FT /evidence="ECO:0007829|PDB:2MUN"
FT HELIX 100..110
FT /evidence="ECO:0007829|PDB:2MUN"
SQ SEQUENCE 112 AA; 12990 MW; 1F1217BB64B6C916 CRC64;
MRIWSLTRIL TFIVIFNFAE AGGECMKKCD SPDMIREIFT RCTMVKRDTQ FSENSGHLIP
KRSVVADNKC ENSLRREIAC GQCRDKVKTD GYFYECCTSD STFKKCQDLL HK
