ID   HM1A_PHLSP              Reviewed;          89 AA.
AC   P0DL57;
DT   14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT   14-OCT-2015, sequence version 1.
DT   25-MAY-2022, entry version 11.
DE   RecName: Full=Mu-theraphotoxin-Phlo1a {ECO:0000303|PubMed:26134258};
DE            Short=Mu-TRTX-Phlo1a {ECO:0000303|PubMed:26134258};
DE   Flags: Precursor;
OS   Phlogius sp. (Tarantula spider).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Mygalomorphae; Theraphosidae; Phlogius; unclassified Phlogius.
OX   NCBI_TaxID=1690075;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 56-87, FUNCTION, MASS
RP   SPECTROMETRY, AMIDATION AT ILE-87, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=26134258; DOI=10.3390/toxins7072494;
RA   Chow C.Y., Cristofori-Armstrong B., Undheim E.A., King G.F., Rash L.D.;
RT   "Three peptide modulators of the human voltage-gated sodium channel 1.7, an
RT   important analgesic target, from the venom of an Australian tarantula.";
RL   Toxins 7:2494-2513(2015).
CC   -!- FUNCTION: Gating-modifier toxin that inhibits voltage-gated sodium
CC       channel Nav by shifting the threshold for channel activation to more
CC       positive potentials. This toxin moderately inhibits human Nav1.7/SCN9A
CC       (IC(50)=459 nM) and weakly inhibits hNav1.2/SCN2A and hNav1.5/SCN5A
CC       (<20% inhibition at 1 uM peptide). Inhibition of Nav1.7 is voltage-
CC       dependent, with lower inhibition at more positive test pulses.
CC       {ECO:0000269|PubMed:26134258}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26134258}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:26134258}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000305|PubMed:26134258}.
CC   -!- MASS SPECTROMETRY: Mass=4105.04; Method=MALDI; Note=Monoisotopic mass.;
CC       Evidence={ECO:0000269|PubMed:26134258};
CC   -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 39 (Jztx-34)
CC       subfamily. {ECO:0000305}.
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DR   AlphaFoldDB; P0DL57; -.
DR   SMR; P0DL57; -.
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   Pfam; PF07740; Toxin_12; 1.
PE   1: Evidence at protein level;
KW   Amidation; Cardiotoxin; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Knottin; Neurotoxin; Secreted; Signal; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PROPEP          23..52
FT                   /evidence="ECO:0000269|PubMed:26134258"
FT                   /id="PRO_0000434301"
FT   CHAIN           53..87
FT                   /note="Mu-theraphotoxin-Phlo1a"
FT                   /evidence="ECO:0000269|PubMed:26134258"
FT                   /id="PRO_0000434302"
FT   MOD_RES         87
FT                   /note="Isoleucine amide"
FT                   /evidence="ECO:0000269|PubMed:26134258"
FT   DISULFID        54..68
FT                   /evidence="ECO:0000250|UniProtKB:P0C247"
FT   DISULFID        61..73
FT                   /evidence="ECO:0000250|UniProtKB:P0C247"
FT   DISULFID        67..81
FT                   /evidence="ECO:0000250|UniProtKB:P0C247"
SQ   SEQUENCE   89 AA;  10085 MW;  1F3AABAE7CBCFF6A CRC64;
     MKVSVLITLA VLGVMFVWTS AAEQEDHGSD RRDSPALLKN LLGEEVFQSE ERACRELLGG
     CSKDSDCCAH LECRKKWPYH CVWDWTIGK