H3A01_CYRHA
ID H3A01_CYRHA Reviewed; 83 AA.
AC D2Y1X9; P83464;
DT 02-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 1.
DT 25-MAY-2022, entry version 37.
DE RecName: Full=Hainantoxin-III 1 {ECO:0000303|PubMed:23703613, ECO:0000303|Ref.5};
DE Short=HnTx-III {ECO:0000303|PubMed:23703613, ECO:0000303|Ref.5};
DE AltName: Full=Hainantoxin-3;
DE AltName: Full=Mu-theraphotoxin-Hhn2a;
DE Short=Mu-TRTX-Hhn2a;
DE AltName: Full=Peptide F7-18.76;
DE Flags: Precursor;
OS Cyriopagopus hainanus (Chinese bird spider) (Haplopelma hainanum).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Haplopelma.
OX NCBI_TaxID=209901;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA / MRNA], PROTEIN SEQUENCE OF
RP 49-81, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom, and Venom gland;
RX PubMed=20192277; DOI=10.1021/pr1000016;
RA Tang X., Zhang Y., Hu W., Xu D., Tao H., Yang X., Li Y., Jiang L.,
RA Liang S.;
RT "Molecular diversification of peptide toxins from the tarantula Haplopelma
RT hainanum (Ornithoctonus hainana) venom based on transcriptomic, peptidomic,
RT and genomic analyses.";
RL J. Proteome Res. 9:2550-2564(2010).
RN [2]
RP PROTEIN SEQUENCE OF 49-81, FUNCTION, SUBCELLULAR LOCATION, AND AMIDATION AT
RP LEU-81.
RC TISSUE=Venom;
RX PubMed=14512091; DOI=10.1016/s0014-2999(03)02190-3;
RA Xiao Y., Liang S.;
RT "Inhibition of neuronal tetrodotoxin-sensitive Na+ channels by two spider
RT toxins: hainantoxin-III and hainantoxin-IV.";
RL Eur. J. Pharmacol. 477:1-7(2003).
RN [3]
RP SUBUNIT, AND MASS SPECTROMETRY.
RA Zhu Q., Liu Z.-H., Liang S.-P.;
RT "Function and solution structure of hainantoxin-III, a potent neuronal TTX-
RT sensitive sodium channel antagonist from Chinese bird spider Selenocosmia
RT hainana.";
RL Submitted (OCT-2002) to UniProtKB.
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, STRUCTURE BY NMR OF 49-81, AND DISULFIDE
RP BONDS.
RC TISSUE=Venom;
RX PubMed=23703613; DOI=10.1074/jbc.m112.426627;
RA Liu Z., Cai T., Zhu Q., Deng M., Li J., Zhou X., Zhang F., Li D., Li J.,
RA Liu Y., Hu W., Liang S.;
RT "Structure and function of hainantoxin-III, a selective antagonist of
RT neuronal tetrodotoxin-sensitive voltage-gated sodium channels isolated from
RT the Chinese bird spider Ornithoctonus hainana.";
RL J. Biol. Chem. 288:20392-20403(2013).
RN [5]
RP STRUCTURE BY NMR OF 49-81, AND DISULFIDE BONDS.
RA Zhu Q., Liu Z., Liang S.;
RT "Three dimensional solution structure of hainantoxin-III by 2D 1H-NMR.";
RL Submitted (JUL-2007) to the PDB data bank.
CC -!- FUNCTION: Selective antagonist of neuronal tetrodotoxin (TTX)-sensitive
CC voltage-gated sodium channels (IC(50)=1270 nM on Nav1.1/SCN1A, 270 nM
CC on Nav1.2/SCN2A, 491 nM on Nav1.3/SCN3A and 232 nM on Nav1.7/SCN9A).
CC This toxin suppress Nav1.7 current amplitude without significantly
CC altering the activation, inactivation, and repriming kinetics. Short
CC extreme depolarizations partially activate the toxin-bound channel,
CC indicating voltage-dependent inhibition of this toxin. This toxin
CC increases the deactivation of the Nav1.7 current after extreme
CC depolarizations. The toxin-Nav1.7 complex is gradually dissociated upon
CC prolonged strong depolarizations in a voltage-dependent manner, and the
CC unbound toxin rebinds to Nav1.7 after a long repolarization. Moreover,
CC analysis of chimeric channels showed that the DIIS3-S4 linker is
CC critical for toxin binding to Nav1.7. These data are consistent with
CC this toxin interacting with Nav1.7 site 4 and trapping the domain II
CC voltage sensor in the closed state. {ECO:0000269|PubMed:23703613}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|Ref.3}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14512091,
CC ECO:0000269|PubMed:23703613}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:14512091, ECO:0000305|PubMed:23703613}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:23703613}.
CC -!- MASS SPECTROMETRY: Mass=3607.6; Method=Electrospray;
CC Evidence={ECO:0000269|Ref.3};
CC -!- MISCELLANEOUS: Has no activity on Nav1.4, Nav1.5, Nav1.8 and Nav1.9
CC sodium and calcium currents. {ECO:0000269|PubMed:14512091,
CC ECO:0000269|PubMed:23703613}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 15 (Hntx-3)
CC subfamily. {ECO:0000305}.
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DR EMBL; GU292856; ADB56672.1; -; mRNA.
DR EMBL; GU293061; ADB56877.1; -; Genomic_DNA.
DR PDB; 2JTB; NMR; -; A=49-81.
DR PDBsum; 2JTB; -.
DR AlphaFoldDB; D2Y1X9; -.
DR SMR; D2Y1X9; -.
DR ArachnoServer; AS000339; mu-theraphotoxin-Hhn2a.
DR EvolutionaryTrace; D2Y1X9; -.
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; Amidation; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Neurotoxin; Presynaptic neurotoxin;
KW Secreted; Signal; Toxin; Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..48
FT /evidence="ECO:0000269|PubMed:14512091,
FT ECO:0000269|PubMed:20192277"
FT /id="PRO_0000400500"
FT PEPTIDE 49..81
FT /note="Hainantoxin-III 1"
FT /evidence="ECO:0000269|PubMed:14512091,
FT ECO:0000269|PubMed:20192277"
FT /id="PRO_0000400501"
FT MOD_RES 81
FT /note="Leucine amide"
FT /evidence="ECO:0000269|PubMed:14512091"
FT DISULFID 50..65
FT /evidence="ECO:0000269|PubMed:23703613, ECO:0000269|Ref.5,
FT ECO:0000312|PDB:2JTB"
FT DISULFID 57..70
FT /evidence="ECO:0000269|PubMed:23703613, ECO:0000269|Ref.5,
FT ECO:0000312|PDB:2JTB"
FT DISULFID 64..77
FT /evidence="ECO:0000269|PubMed:23703613, ECO:0000269|Ref.5,
FT ECO:0000312|PDB:2JTB"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:2JTB"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:2JTB"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:2JTB"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:2JTB"
SQ SEQUENCE 83 AA; 9195 MW; AEE1DBFDFB29B622 CRC64;
MKASMFLALA GLVLLFVVGY ASESEEKEFP RELLSKIFAV DDFKGEERGC KGFGDSCTPG
KNECCPNYAC SSKHKWCKVY LGK
