ID   HSTX1_HAESL             Reviewed;          49 AA.
AC   A0A2L1DGG0;
DT   07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT   07-APR-2021, sequence version 2.
DT   25-MAY-2022, entry version 12.
DE   RecName: Full=Peptide HSTX-I {ECO:0000303|PubMed:29559913, ECO:0000303|PubMed:32524995};
DE   Flags: Precursor;
OS   Haemadipsa sylvestris (Indian leech).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Annelida; Clitellata;
OC   Hirudinea; Hirudinida; Hirudiniformes; Haemadipsidae; Haemadipsa.
OX   NCBI_TaxID=13555;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 26-48, MASS SPECTROMETRY,
RP   3D-STRUCTURE MODELING, SUBCELLULAR LOCATION, DISULFIDE BONDS, AND AMIDATION
RP   AT ILE-48.
RC   TISSUE=Salivary gland;
RX   PubMed=29559913; DOI=10.3389/fphar.2018.00186;
RA   Wang G., Long C., Liu W., Xu C., Zhang M., Li Q., Lu Q., Meng P., Li D.,
RA   Rong M., Sun Z., Luo X., Lai R.;
RT   "Novel sodium channel inhibitor from leeches.";
RL   Front. Pharmacol. 9:186-186(2018).
RN   [2] {ECO:0007744|PDB:6WQR}
RP   STRUCTURE BY NMR OF 26-48, FUNCTION, SYNTHESIS OF 26-48, AND DISULFIDE
RP   BONDS.
RX   PubMed=32524995; DOI=10.1016/j.bcp.2020.114082;
RA   McMahon K.L., Tay B., Deuis J.R., Tanaka B.S., Peigneur S., Jin A.H.,
RA   Tytgat J., Waxman S.G., Dib-Hajj S.D., Vetter I., Schroeder C.I.;
RT   "Pharmacological activity and NMR solution structure of the leech peptide
RT   HSTX-I.";
RL   Biochem. Pharmacol. 181:114082-114082(2020).
CC   -!- FUNCTION: Leech salivary gland peptide with unknown function
CC       (PubMed:32524995). It was originally described as exhibiting analgesic
CC       function by specifically inhibiting rodent Nav1.8/SCN10A and
CC       Nav1.9/SCN11A voltage-gated sodium channels, as well as showing
CC       analgesic activities in several mouse models (PubMed:29559913). In a
CC       second study, the synthetic peptide has been shown as having very weak
CC       activity on Nav1.8/SCN10A at the highest concentration tested (90 uM)
CC       and as being only very modestly active at hNav1.9/SCN11A, with a modest
CC       peak current size reduction (~19%) at high concentrations (10 uM)
CC       (PubMed:32524995). In addition, this second study reports no analgesic
CC       activity in a mouse model of inflammatory pain (PubMed:32524995).
CC       {ECO:0000269|PubMed:29559913, ECO:0000269|PubMed:32524995}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in salivary glands. Highly expressed in
CC       the head, body and tail with a 2-3-fold higher expression in the head.
CC       {ECO:0000269|PubMed:29559913}.
CC   -!- MASS SPECTROMETRY: Mass=2621.14; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:29559913};
CC   -!- MISCELLANEOUS: Does not show effect on voltage-gated calcium channels,
CC       potassium channels, and tetrodotoxin-sensitive sodium channels
CC       (PubMed:29559913). Does not show activity on Nav1.7/SCN9A, and shows
CC       very weak activity on cation channel TRPA1 (PubMed:32524995).
CC       {ECO:0000269|PubMed:29559913, ECO:0000269|PubMed:32524995}.
CC   -!- SIMILARITY: Belongs to the annelide toxin family. {ECO:0000305}.
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DR   EMBL; MG786826; AVC68883.1; -; mRNA.
DR   PDB; 6WQR; NMR; -; A=26-48.
DR   PDBsum; 6WQR; -.
DR   AlphaFoldDB; A0A2L1DGG0; -.
DR   BMRB; A0A2L1DGG0; -.
DR   SMR; A0A2L1DGG0; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Direct protein sequencing; Disulfide bond;
KW   Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   PROPEP          22..28
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000452215"
FT   PEPTIDE         26..48
FT                   /note="Peptide HSTX-I"
FT                   /evidence="ECO:0000269|PubMed:29559913"
FT                   /id="PRO_5014992413"
FT   MOD_RES         48
FT                   /note="Isoleucine amide"
FT                   /evidence="ECO:0000269|PubMed:29559913"
FT   DISULFID        27..39
FT                   /evidence="ECO:0000269|PubMed:29559913,
FT                   ECO:0000269|PubMed:32524995, ECO:0007744|PDB:6WQR"
FT   DISULFID        33..44
FT                   /evidence="ECO:0000269|PubMed:29559913,
FT                   ECO:0000269|PubMed:32524995, ECO:0007744|PDB:6WQR"
FT   CONFLICT        8
FT                   /note="L -> LVFL (in Ref. 1; AVC68883)"
FT                   /evidence="ECO:0000305"
FT   HELIX           30..33
FT                   /evidence="ECO:0007829|PDB:6WQR"
FT   STRAND          38..40
FT                   /evidence="ECO:0007829|PDB:6WQR"
FT   STRAND          43..45
FT                   /evidence="ECO:0007829|PDB:6WQR"
SQ   SEQUENCE   49 AA;  5409 MW;  38DF53B293A9C102 CRC64;
     MRTLLVFLLL AIFVAVLIGN VQVEAACKEY WECGAFLFCI EGICVPMIG