ID   HD1A_CYRDO              Reviewed;          35 AA.
AC   A0A0J9X1W9;
DT   25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2017, sequence version 2.
DT   25-MAY-2022, entry version 25.
DE   RecName: Full=Mu-theraphotoxin-Hd1a {ECO:0000303|PubMed:25754331};
DE            Short=Mu-TRTX-Hd1a {ECO:0000303|PubMed:25754331};
OS   Cyriopagopus doriae (Tarantula spider) (Haplopelma doriae).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Mygalomorphae; Theraphosidae; Cyriopagopus.
OX   NCBI_TaxID=2024410;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, MASS SPECTROMETRY, STRUCTURE BY NMR, DISULFIDE
RP   BONDS, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=25754331; DOI=10.1111/bph.13081;
RA   Klint J.K., Smith J.J., Vetter I., Rupasinghe D.B., Er S.Y., Senff S.,
RA   Herzig V., Mobli M., Lewis R.J., Bosmans F., King G.F.;
RT   "Seven novel modulators of the analgesic target NaV 1.7 uncovered using a
RT   high-throughput venom-based discovery approach.";
RL   Br. J. Pharmacol. 172:2445-2458(2015).
CC   -!- FUNCTION: Gating-modifier toxin that reversibly and voltage-
CC       independently inhibits human Nav1.1/SCN1A and Nav1.7/SCN9A (IC(50)=111
CC       nM) (PubMed:25754331). It also shows moderate inhibition on
CC       Nav1.2/SCN2A (1 uM inhibits current by 55%), Nav1.6/SCN8A (31%),
CC       Nav1.3/SCN5A (27%) and Nav1.4/SCN4A (23%) (PubMed:25754331). This toxin
CC       inhibits Nav1.7/SCN9A by interacting with the S3b-S4 paddle motif in
CC       channel domain II (PubMed:25754331). {ECO:0000269|PubMed:25754331}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25754331}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:25754331}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000269|PubMed:25754331}.
CC   -!- MASS SPECTROMETRY: Mass=3819.9; Method=MALDI; Note=Monoisotopic mass.;
CC       Evidence={ECO:0000269|PubMed:25754331};
CC   -!- MISCELLANEOUS: Does not inhibit Nav1.5/SCN5A, Nav1.8/SCN10A, and
CC       presumably not Nav1.9/SCN11A voltage-gated sodium channels.
CC       {ECO:0000269|PubMed:25754331}.
CC   -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 22 (Htx-4)
CC       subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Biological Magnetic Resonance Data Bank;
CC       URL="http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=19998";
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   PDB; 2MPQ; NMR; -; A=1-35.
DR   PDBsum; 2MPQ; -.
DR   AlphaFoldDB; A0A0J9X1W9; -.
DR   SMR; A0A0J9X1W9; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR011696; Huwentoxin-1.
DR   InterPro; IPR013140; Huwentoxin_CS1.
DR   Pfam; PF07740; Toxin_12; 1.
DR   PROSITE; PS60021; HWTX_1; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Knottin; Secreted; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..35
FT                   /note="Mu-theraphotoxin-Hd1a"
FT                   /evidence="ECO:0000269|PubMed:25754331"
FT                   /id="PRO_0000441850"
FT   DISULFID        2..17
FT                   /evidence="ECO:0000269|PubMed:25754331,
FT                   ECO:0000312|PDB:2MPQ"
FT   DISULFID        9..24
FT                   /evidence="ECO:0000269|PubMed:25754331,
FT                   ECO:0000312|PDB:2MPQ"
FT   DISULFID        16..31
FT                   /evidence="ECO:0000269|PubMed:25754331,
FT                   ECO:0000312|PDB:2MPQ"
FT   HELIX           18..20
FT                   /evidence="ECO:0007829|PDB:2MPQ"
FT   STRAND          22..24
FT                   /evidence="ECO:0007829|PDB:2MPQ"
FT   TURN            26..28
FT                   /evidence="ECO:0007829|PDB:2MPQ"
FT   STRAND          30..33
FT                   /evidence="ECO:0007829|PDB:2MPQ"
SQ   SEQUENCE   35 AA;  3828 MW;  831F6769C58D39CD CRC64;
     ACLGFGKSCN PSNDQCCKSS SLACSTKHKW CKYEL