TXH4_CYRSC
ID TXH4_CYRSC Reviewed; 89 AA.
AC P83303; B3FIU7; B3FIU8; B3FIU9; Q86C52;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 2.
DT 25-MAY-2022, entry version 101.
DE RecName: Full=Huwentoxin-IV {ECO:0000303|PubMed:14757201};
DE Short=HwTx-IV {ECO:0000303|PubMed:14757201, ECO:0000303|PubMed:29703751};
DE AltName: Full=Huwentoxin-4 {ECO:0000305};
DE AltName: Full=Huwentoxin-IVa {ECO:0000312|EMBL:ABY77744.1};
DE Short=HWTX-IVa {ECO:0000312|EMBL:ABY77744.1};
DE AltName: Full=Huwentoxin-IVb {ECO:0000312|EMBL:ABY77745.1};
DE Short=HWTX-IVb {ECO:0000312|EMBL:ABY77745.1};
DE AltName: Full=Huwentoxin-IVc {ECO:0000312|EMBL:ABY77746.1};
DE Short=HWTX-IVc {ECO:0000312|EMBL:ABY77746.1};
DE AltName: Full=Mu-theraphotoxin-Hs2a {ECO:0000303|PubMed:23760503};
DE Short=Mu-TRTX-Hs2a {ECO:0000303|PubMed:23760503};
DE Flags: Precursor;
OS Cyriopagopus schmidti (Chinese bird spider) (Haplopelma schmidti).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Cyriopagopus.
OX NCBI_TaxID=29017;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=14757201; DOI=10.1016/j.toxicon.2003.08.007;
RA Diao J., Lin Y., Tang J., Liang S.-P.;
RT "cDNA sequence analysis of seven peptide toxins from the spider
RT Selenocosmia huwena.";
RL Toxicon 42:715-723(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-89.
RC TISSUE=Venom gland;
RX PubMed=18482741; DOI=10.1016/j.toxicon.2008.03.024;
RA Jiang L., Peng L., Chen J., Zhang Y., Xiong X., Liang S.;
RT "Molecular diversification based on analysis of expressed sequence tags
RT from the venom glands of the Chinese bird spider Ornithoctonus huwena.";
RL Toxicon 51:1479-1489(2008).
RN [3]
RP PROTEIN SEQUENCE OF 53-87, STRUCTURE BY NMR OF 53-87, FUNCTION, DISULFIDE
RP BONDS, AMIDATION AT ILE-87, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=12228241; DOI=10.1074/jbc.m204063200;
RA Peng K., Shu Q., Liang S.-P.;
RT "Function and solution structure of huwentoxin-IV, a potent neuronal
RT tetrodotoxin (TTX)-sensitive sodium channel antagonist from Chinese bird
RT spider Selenocosmia huwena.";
RL J. Biol. Chem. 277:47564-47571(2002).
RN [4]
RP PROTEIN SEQUENCE OF 53-59, PYROGLUTAMATE FORMATION AT GLU-53, AND MASS
RP SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=23826086; DOI=10.1371/journal.pone.0065984;
RA Rong M., Duan Z., Chen J., Li J., Xiao Y., Liang S.;
RT "Native pyroglutamation of huwentoxin-IV: a post-translational modification
RT that increases the trapping ability to the sodium channel.";
RL PLoS ONE 8:E65984-E65984(2013).
RN [5]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=18628201; DOI=10.1074/jbc.m708447200;
RA Xiao Y., Bingham J.-P., Zhu W., Moczydlowski E., Liang S., Cummins T.R.;
RT "Tarantula huwentoxin-IV inhibits neuronal sodium channels by binding to
RT receptor site 4 and trapping the domain II voltage sensor in the closed
RT configuration.";
RL J. Biol. Chem. 283:27300-27313(2008).
RN [6]
RP FUNCTION, SYNTHESIS OF 53-87, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=18054060; DOI=10.1016/j.toxicon.2007.09.008;
RA Xiao Y., Luo X., Kuang F., Deng M., Wang M., Zeng X., Liang S.;
RT "Synthesis and characterization of huwentoxin-IV, a neurotoxin inhibiting
RT central neuronal sodium channels.";
RL Toxicon 51:230-239(2008).
RN [7]
RP FUNCTION.
RX PubMed=20855463; DOI=10.1124/mol.110.066332;
RA Xiao Y., Blumenthal K., Jackson J.O. II, Liang S., Cummins T.R.;
RT "The tarantula toxins ProTx-II and huwentoxin-IV differentially interact
RT with human Nav1.7 voltage sensors to inhibit channel activation and
RT inactivation.";
RL Mol. Pharmacol. 78:1124-1134(2010).
RN [8]
RP FUNCTION.
RX PubMed=21659528; DOI=10.1074/jbc.m111.246876;
RA Xiao Y., Jackson J.O. II, Liang S., Cummins T.R.;
RT "Common molecular determinants of tarantula huwentoxin-IV inhibition of Na+
RT channel voltage sensors in domains II and IV.";
RL J. Biol. Chem. 286:27301-27310(2011).
RN [9]
RP FUNCTION, SYNTHESIS OF 53-87, AND MUTAGENESIS OF GLU-53; GLU-56 AND TYR-85.
RX PubMed=23523779; DOI=10.1016/j.peptides.2013.03.011;
RA Revell J.D., Lund P.E., Linley J.E., Metcalfe J., Burmeister N.,
RA Sridharan S., Jones C., Jermutus L., Bednarek M.A.;
RT "Potency optimization of Huwentoxin-IV on hNav1.7: a neurotoxin TTX-S
RT sodium-channel antagonist from the venom of the Chinese bird-eating spider
RT Selenocosmia huwena.";
RL Peptides 44:40-46(2013).
RN [10]
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 [11]
RP FUNCTION, AND SYNTHESIS.
RX PubMed=29703751; DOI=10.1074/jbc.ra118.002553;
RA Agwa A.J., Peigneur S., Chow C.Y., Lawrence N., Craik D.J., Tytgat J.,
RA King G.F., Henriques S.T., Schroeder C.I.;
RT "Gating modifier toxins isolated from spider venom: modulation of voltage-
RT gated sodium channels and the role of lipid membranes.";
RL J. Biol. Chem. 293:9041-9052(2018).
RN [12]
RP FUNCTION, AND SYNTHESIS OF 53-87.
RX PubMed=29483648; DOI=10.1038/s41594-018-0033-9;
RA Correnti C.E., Gewe M.M., Mehlin C., Bandaranayake A.D., Johnsen W.A.,
RA Rupert P.B., Brusniak M.Y., Clarke M., Burke S.E., De Van Der Schueren W.,
RA Pilat K., Turnbaugh S.M., May D., Watson A., Chan M.K., Bahl C.D.,
RA Olson J.M., Strong R.K.;
RT "Screening, large-scale production and structure-based classification of
RT cystine-dense peptides.";
RL Nat. Struct. Mol. Biol. 25:270-278(2018).
RN [13]
RP FUNCTION ON NAV1.7/SCN9A, AND SYNTHESIS OF 53-87.
RX PubMed=31234412; DOI=10.3390/toxins11060367;
RA Nicolas S., Zoukimian C., Bosmans F., Montnach J., Diochot S., Cuypers E.,
RA De Waard S., Beroud R., Mebs D., Craik D., Boturyn D., Lazdunski M.,
RA Tytgat J., De Waard M.;
RT "Chemical synthesis, proper folding, Nav channel selectivity profile and
RT analgesic properties of the spider peptide Phlotoxin 1.";
RL Toxins 11:0-0(2019).
RN [14]
RP STRUCTURE BY NMR OF 53-87, FUNCTION, AND MUTAGENESIS OF GLU-56; PHE-58;
RP PRO-63; ASP-66; LEU-74; SER-77; TRP-82; LYS-84; TYR-85 AND ILE-87.
RX PubMed=23760503; DOI=10.1074/jbc.m113.461392;
RA Minassian N.A., Gibbs A., Shih A.Y., Liu Y., Neff R.A., Sutton S.W.,
RA Mirzadegan T., Connor J., Fellows R., Husovsky M., Nelson S., Hunter M.J.,
RA Flinspach M., Wickenden A.D.;
RT "Analysis of the structural and molecular basis of voltage-sensitive sodium
RT channel inhibition by the spider toxin huwentoxin-IV (mu-TRTX-Hh2a).";
RL J. Biol. Chem. 288:22707-22720(2013).
RN [15]
RP STRUCTURE BY NMR OF 53-87 OF HUWENTOXIN-IV; M-HUWENTOXIN-IV AND
RP G-HUWENTOXIN-IV, FUNCTION, SYNTHESIS OF 53-87 (HUWENTOXIN-IV;
RP MHUWENTOXIN-IV AND G-HUWENTOXIN-IV), AND MUTAGENESIS OF GLU-53; GLU-56;
RP PHE-58 AND TYR-85.
RX PubMed=28115115; DOI=10.1016/j.bbamem.2017.01.020;
RA Agwa A.J., Lawrence N., Deplazes E., Cheneval O., Chen R.M., Craik D.J.,
RA Schroeder C.I., Henriques S.T.;
RT "Spider peptide toxin HwTx-IV engineered to bind to lipid membranes has an
RT increased inhibitory potency at human voltage-gated sodium channel
RT hNaV1.7.";
RL Biochim. Biophys. Acta 1859:835-844(2017).
RN [16]
RP STRUCTURE BY NMR OF M3-HUWENTOXIN-IV MUTANT, AND MUTAGENESIS OF GLU-53;
RP GLU-56 AND TYR-85.
RX PubMed=28301520; DOI=10.1371/journal.pone.0173551;
RA Rahnama S., Deuis J.R., Cardoso F.C., Ramanujam V., Lewis R.J., Rash L.D.,
RA King G.F., Vetter I., Mobli M.;
RT "The structure, dynamics and selectivity profile of a NaV1.7 potency-
RT optimised huwentoxin-IV variant.";
RL PLoS ONE 12:E0173551-E0173551(2017).
RN [17]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.2 ANGSTROMS) IN COMPLEX WITH SCN9A;
RP SCN1B AND SCN2B.
RX PubMed=30765606; DOI=10.1126/science.aaw2493;
RA Shen H., Liu D., Wu K., Lei J., Yan N.;
RT "Structures of human Nav1.7 channel in complex with auxiliary subunits and
RT animal toxins.";
RL Science 363:1303-1308(2019).
CC -!- FUNCTION: This lethal neurotoxin (without cyclization at position 53)
CC inhibits neuronal voltage-gated sodium channel Nav1.2/SCN2A (IC(50)=10-
CC 150 nM), rNav1.3/SCN3A (IC(50)=338 nM), Nav1.6/SCN8A (IC(50)=117 nM),
CC and hNav1.7/SCN9A (IC(50)=9.6-33 nM) (PubMed:18628201, PubMed:20855463,
CC PubMed:25658507, PubMed:29703751,PubMed:31234412, PubMed:23760503). It
CC inhibits activation of sodium channel by trapping the voltage sensor of
CC domain II (DIIS4) in the closed configuration (PubMed:18628201,
CC PubMed:23760503). The toxin neither shifts the Nav1.7/SCN9A activation
CC curve nor modifies the slope factor (PubMed:20855463). It does not slow
CC fast-inactivation of hNav1.7/SCN9A channels (PubMed:20855463). In
CC addition, it has only a weak affinity for lipid membranes
CC (PubMed:18054060, PubMed:29703751, PubMed:28115115). This toxin also
CC exists with a pyroglutamate at position 53 (PubMed:23826086). The sole
CC difference observed between modified (mHwTx-IV) and unmodified toxins
CC is that moderate or high depolarization voltages (200 mV) permit the
CC unmodified toxin to dissociate, whereas mHwTx-IV toxin does not
CC dissociate, even at high depolarization voltages (PubMed:23826086).
CC These data indicate that mHwTx-IV strongly binds to voltage sensor of
CC sodium channel even at extreme depolarization voltages
CC (PubMed:23826086). {ECO:0000269|PubMed:12228241,
CC ECO:0000269|PubMed:18054060, ECO:0000269|PubMed:18628201,
CC ECO:0000269|PubMed:20855463, ECO:0000269|PubMed:21659528,
CC ECO:0000269|PubMed:23523779, ECO:0000269|PubMed:23760503,
CC ECO:0000269|PubMed:25658507, ECO:0000269|PubMed:28115115,
CC ECO:0000269|PubMed:29483648}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12228241}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:12228241}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:12228241, ECO:0000269|PubMed:23760503,
CC ECO:0000269|PubMed:28115115}.
CC -!- PTM: Two forms of huwentoxin-IV exist in the venom of H.schmidti, a
CC non-N-terminally modified (HwTx-IV) and a naturally modified peptide
CC with pyroglutamic acid residue at position 53 (mHwTx-IV). mHwTx-IV
CC shows no observable difference with the unmodified toxin when applied
CC to the TTX-S sodium channel of DRG neuron (IC(50)~50 nM) or when tested
CC on hNav1.7/SCN9A (IC(50)=30.8 nM) (PubMed:23826086, PubMed:28115115).
CC In addition, similarly to the unmodified toxin, mHwTx-IV has only a
CC weak affinity for lipid membranes (PubMed:28115115). However, in
CC contrast with HwTx-IV, which dissociates at moderate and high
CC depolarization voltages (50-200 mV), mHwTx-IV inhibition of TTX-
CC sensitive sodium channels is not reversed by strong depolarization
CC voltages (PubMed:23826086). {ECO:0000269|PubMed:23826086,
CC ECO:0000269|PubMed:28115115}.
CC -!- MASS SPECTROMETRY: Mass=4089.64; Method=MALDI; Note=mhuwentoxin-IV
CC (with pyrrolidone carboxylic acid (Glu) at position 53).;
CC Evidence={ECO:0000269|PubMed:23826086};
CC -!- MASS SPECTROMETRY: Mass=4107.94; Method=MALDI; Note=huwentoxin-IV (with
CC unmodified Glu at position 53).;
CC Evidence={ECO:0000269|PubMed:23826086};
CC -!- MASS SPECTROMETRY: Mass=4107.5; Method=MALDI; Note=huwentoxin-IV (with
CC unmodified Glu at position 53).;
CC Evidence={ECO:0000269|PubMed:18054060};
CC -!- MISCELLANEOUS: Shows a weak or no inhibition on rNav1.4/SCN4A
CC (IC(50)=3.9->10 uM) and hNav1.5/SCN5A sodium channels (IC(50)=>10-25
CC uM) (PubMed:18628201, PubMed:25658507). This toxin has also been shown
CC to weakly inhibit Kv11.1/KCNH2/ERG1, Kv1.2/KCNA2 and Kv1.3/KCNA3
CC (PubMed:29483648). {ECO:0000269|PubMed:18628201,
CC ECO:0000269|PubMed:25658507, ECO:0000269|PubMed:29483648}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 22 (Htx-4)
CC subfamily. {ECO:0000305}.
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DR EMBL; AY263707; AAP33074.1; -; mRNA.
DR EMBL; EU195291; ABY77744.1; -; mRNA.
DR EMBL; EU195292; ABY77745.1; -; mRNA.
DR EMBL; EU195293; ABY77746.1; -; mRNA.
DR PDB; 1MB6; NMR; -; A=53-87.
DR PDB; 2M4X; NMR; -; A=53-87.
DR PDB; 2M4Z; NMR; -; A=53-87.
DR PDB; 2M50; NMR; -; A=53-87.
DR PDB; 5T3M; NMR; -; A=53-87.
DR PDB; 5TLR; NMR; -; A=53-87.
DR PDB; 6W6O; EM; 3.20 A; C/E/G/I=53-87.
DR PDB; 7K48; EM; 3.60 A; E/F/G/H=53-87.
DR PDBsum; 1MB6; -.
DR PDBsum; 2M4X; -.
DR PDBsum; 2M4Z; -.
DR PDBsum; 2M50; -.
DR PDBsum; 5T3M; -.
DR PDBsum; 5TLR; -.
DR PDBsum; 6W6O; -.
DR PDBsum; 7K48; -.
DR AlphaFoldDB; P83303; -.
DR BMRB; P83303; -.
DR SMR; P83303; -.
DR TCDB; 8.B.3.1.3; the huwentoxin-1 (huwentoxin-1) family.
DR ArachnoServer; AS000332; mu-theraphotoxin-Hs2a.
DR EvolutionaryTrace; P83303; -.
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 Pyrrolidone carboxylic acid; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..52
FT /evidence="ECO:0000269|PubMed:12228241"
FT /id="PRO_0000035560"
FT CHAIN 53..87
FT /note="Huwentoxin-IV"
FT /evidence="ECO:0000269|PubMed:12228241"
FT /id="PRO_0000035561"
FT SITE 58
FT /note="Binds to the extracellular loop of voltage sensor
FT domain II of sodium channels (Nav1.2/SCN2A and
FT Nav1.7/SCN9A)"
FT /evidence="ECO:0000305|PubMed:23760503"
FT SITE 78
FT /note="Binds to the extracellular loop of voltage sensor
FT domain II of sodium channels (Nav1.2/SCN2A and
FT Nav1.7/SCN9A)"
FT /evidence="ECO:0000305|PubMed:23760503"
FT SITE 79
FT /note="Binds to the extracellular loop of voltage sensor
FT domain II of sodium channels (Nav1.2/SCN2A and
FT Nav1.7/SCN9A)"
FT /evidence="ECO:0000305|PubMed:23760503"
FT SITE 82
FT /note="Binds to the extracellular loop of voltage sensor
FT domain II of sodium channels (Nav1.2/SCN2A and
FT Nav1.7/SCN9A)"
FT /evidence="ECO:0000305|PubMed:23760503"
FT SITE 84
FT /note="Binds to the extracellular loop of voltage sensor
FT domain II of sodium channels (Nav1.2/SCN2A and
FT Nav1.7/SCN9A)"
FT /evidence="ECO:0000305|PubMed:23760503"
FT MOD_RES 53
FT /note="Pyrrolidone carboxylic acid (Glu); partial"
FT /evidence="ECO:0000269|PubMed:23826086"
FT MOD_RES 87
FT /note="Isoleucine amide"
FT /evidence="ECO:0000269|PubMed:12228241"
FT DISULFID 54..69
FT /evidence="ECO:0000269|PubMed:12228241,
FT ECO:0000312|PDB:1MB6, ECO:0000312|PDB:2M4X,
FT ECO:0000312|PDB:5TLR"
FT DISULFID 61..76
FT /evidence="ECO:0000269|PubMed:12228241,
FT ECO:0000312|PDB:1MB6, ECO:0000312|PDB:2M4X,
FT ECO:0000312|PDB:5TLR"
FT DISULFID 68..83
FT /evidence="ECO:0000269|PubMed:12228241,
FT ECO:0000312|PDB:1MB6, ECO:0000312|PDB:2M4X,
FT ECO:0000312|PDB:5TLR"
FT MUTAGEN 53..56
FT /note="ECLE->ACLA: 6-fold increase in ability to inhibit
FT hNav1.7/SCN9A. 28-fold increase in ability to inhibit
FT hNav1.7/SCN9A; when associated with W-85."
FT /evidence="ECO:0000269|PubMed:23523779"
FT MUTAGEN 53..56
FT /note="ECLE->GCLG: 34-fold increase in ability to inhibit
FT hNav1.7/SCN9A. In m3-huwentoxin-IV; 43-fold increase in
FT ability to inhibit hNav1.7/SCN9A. In m3-huwentoxin-IV;
FT potently inhibits Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.3/SCN3A,
FT Nav1.6/SCN8A and Nav1.7/SCN9A. In gHuwentoxin-IV; shows
FT higher affinity for lipid membranes and a 4-fold increase
FT in ability to inhibit hNav1.7/SCN9A compared to both
FT huwentoxin-IV and mhuwentoxin-IV."
FT /evidence="ECO:0000269|PubMed:23523779,
FT ECO:0000269|PubMed:28115115, ECO:0000269|PubMed:28301520"
FT MUTAGEN 53
FT /note="E->A: 2.8-fold increase in ability to inhibit
FT hNav1.7/SCN9A, and no change in activity on hNav1.5/SCN5A."
FT /evidence="ECO:0000269|PubMed:23523779"
FT MUTAGEN 56
FT /note="E->A: No change in activity on both Nav1.2/SCN2A and
FT hNav1.5/SCN5A, and contreversial activity on Nav1.7/SCN9A.
FT Small increase in ability to inhibit Nav1.7/SCN9A
FT (according to PMID:23760503), and 1.5-fold decrease in
FT ability to inhibit hNav1.7/SCN9A (according to
FT PMID:23523779)."
FT /evidence="ECO:0000269|PubMed:23523779,
FT ECO:0000269|PubMed:23760503"
FT MUTAGEN 58
FT /note="F->A: Important decrease in ability to inhibit
FT Nav1.2/SCN2A, and small decrease in ability to inhibit
FT Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23760503"
FT MUTAGEN 58
FT /note="F->W: In gHuwentoxin-IV; shows higher affinity for
FT lipid membranes and a 4-fold increase in ability to inhibit
FT hNav1.7/SCN9A compared to both huwentoxin-IV and
FT mhuwentoxin-IV."
FT /evidence="ECO:0000269|PubMed:28115115"
FT MUTAGEN 63
FT /note="P->A: Important decrease in ability to inhibit both
FT Nav1.2/SCN2A and Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23760503"
FT MUTAGEN 66
FT /note="D->A: Important decrease in ability to inhibit both
FT Nav1.2/SCN2A and Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23760503"
FT MUTAGEN 74
FT /note="L->A: Important decrease in ability to inhibit both
FT Nav1.2/SCN2A and Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23760503"
FT MUTAGEN 77
FT /note="S->A: Important decrease in ability to inhibit both
FT Nav1.2/SCN2A and Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23760503"
FT MUTAGEN 78
FT /note="R->A: Important decrease in ability to inhibit
FT Nav1.2/SCN2A, and no change in activity on Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23760503"
FT MUTAGEN 79
FT /note="K->A: Important decrease in ability to inhibit
FT Nav1.2/SCN2A, and no change in activity on Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23760503"
FT MUTAGEN 81
FT /note="R->A: Small decrease in ability to inhibit
FT Nav1.2/SCN2A, and no change in activity on Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23760503"
FT MUTAGEN 82
FT /note="W->A: Almost complete loss in ability to inhibit
FT both Nav1.2/SCN2A and Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23760503"
FT MUTAGEN 84
FT /note="K->A: Almost complete loss in ability to inhibit
FT both Nav1.2/SCN2A and Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23760503"
FT MUTAGEN 85
FT /note="Y->A: Important decrease in ability to inhibit both
FT Nav1.2/SCN2A and Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23760503"
FT MUTAGEN 85
FT /note="Y->W: 12-fold increase in ability to inhibit
FT hNav1.7/SCN9A, and no change in activity on hNav1.5/SCN5A.
FT In m3-huwentoxin-IV; 43-fold increase in ability to inhibit
FT hNav1.7/SCN9A. In m3-huwentoxin-IV; potently inhibits
FT Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.6/SCN8A and
FT Nav1.7/SCN9A. In gHuwentoxin-IV; shows higher affinity for
FT lipid membranes and a 4-fold increase in ability to inhibit
FT hNav1.7/SCN9A compared to both huwentoxin-IV and
FT mhuwentoxin-IV."
FT /evidence="ECO:0000269|PubMed:23523779,
FT ECO:0000269|PubMed:28115115, ECO:0000269|PubMed:28301520"
FT MUTAGEN 87
FT /note="I->A: Small decrease in ability to inhibit both
FT Nav1.2/SCN2A and Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23760503"
FT CONFLICT 17
FT /note="L -> Q (in Ref. 2; ABY77746)"
FT /evidence="ECO:0000305|PubMed:18482741"
FT CONFLICT 85
FT /note="Y -> C (in Ref. 2; ABY77745)"
FT /evidence="ECO:0000305|PubMed:18482741"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:2M4Z"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:6W6O"
FT TURN 70..73
FT /evidence="ECO:0007829|PDB:6W6O"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:6W6O"
FT STRAND 78..85
FT /evidence="ECO:0007829|PDB:6W6O"
SQ SEQUENCE 89 AA; 9997 MW; 39CCC6FC1ADCBC75 CRC64;
MVNMKASMFL ALAGLVLLFV VCYASESEEK EFSNELLSSV LAVDDNSKGE ERECLEIFKA
CNPSNDQCCK SSKLVCSRKT RWCKYQIGK
