H1A01_CYRHA
ID H1A01_CYRHA Reviewed; 83 AA.
AC D2Y1X6; P83591;
DT 02-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 1.
DT 25-MAY-2022, entry version 33.
DE RecName: Full=Mu-theraphotoxin-Hhn2b 1 {ECO:0000305|PubMed:26429937};
DE Short=Mu-TRTX-Hhn2b {ECO:0000303|PubMed:26429937};
DE AltName: Full=Hainantoxin-I {ECO:0000303|PubMed:12727268, ECO:0000303|PubMed:14675784, ECO:0000303|PubMed:20192277};
DE Short=HnTx-I {ECO:0000303|PubMed:12727268, ECO:0000303|PubMed:14675784, ECO:0000303|PubMed:20192277};
DE AltName: Full=Peptide F5-19.03;
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 MRNA], PROTEIN SEQUENCE OF 49-81, AND
RP 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.
RC TISSUE=Venom;
RX PubMed=12727268; DOI=10.1016/s0041-0101(02)00280-5;
RA Xiao Y.-C., Liang S.-P.;
RT "Purification and characterization of Hainantoxin-V, a tetrodotoxin-
RT sensitive sodium channel inhibitor from the venom of the spider
RT Selenocosmia hainana.";
RL Toxicon 41:643-650(2003).
RN [3]
RP SEQUENCE REVISION TO 78-81, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, MASS
RP SPECTROMETRY, DISULFIDE BONDS, AMIDATION AT LEU-81, AND STRUCTURE BY NMR OF
RP 48-81.
RC TISSUE=Venom;
RX PubMed=14675784; DOI=10.1016/s0014-5793(03)01303-6;
RA Li D.-L., Xiao Y.-C., Hu W.-J., Xie J.-Y., Bosmans F., Tytgat J.,
RA Liang S.-P.;
RT "Function and solution structure of hainantoxin-I, a novel insect sodium
RT channel inhibitor from the Chinese bird spider Selenocosmia hainana.";
RL FEBS Lett. 555:616-622(2003).
RN [4]
RP STRUCTURE BY NMR OF 48-81 OF WILD-TYPE AND G54W/N71S MUTANT, FUNCTION,
RP RECOMBINANT EXPRESSION OF 48-81, AND MUTAGENESIS OF LYS-51; GLY-54; ASN-71
RP AND VAL-79.
RX PubMed=26429937; DOI=10.1124/mol.115.100784;
RA Klint J.K., Chin Y.K., Mobli M.;
RT "Rational engineering defines a molecular switch that is essential for
RT activity of spider-venom peptides against the analgesics target NaV1.7.";
RL Mol. Pharmacol. 88:1002-1010(2015).
CC -!- FUNCTION: Weakly blocks the rat SCN2A/SCN1B (Nav1.2/beta-1) sodium
CC channel (IC(50)=68 uM) and the insect sodium channel para/tipE
CC (IC(50)=4.3 uM), without altering the activation or inactivation
CC kinetics (depressant toxin). {ECO:0000269|PubMed:14675784,
CC ECO:0000269|PubMed:26429937}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:14675784}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14675784}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000269|PubMed:14675784}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:14675784, ECO:0000269|PubMed:26429937}.
CC -!- MASS SPECTROMETRY: Mass=3608.02; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:14675784};
CC -!- MISCELLANEOUS: Has no effect on mammalian SCN3A/SCN1B (Nav1.3/beta-1),
CC SCN4A (Nav1.4), SCN5A/SCN1B (Nav1.5/beta-1), and SCN9A/SCN1B
CC (Nav1.7/beta-1) (PubMed:14675784, PubMed:26429937). Has also no effect
CC on sodium subtypes in rat DRG neurons containing Nav1.1/SCN1A,
CC Nav1.6/SCN8A, Nav1.7/SCN9A, Nav1.8/SCN10A and Nav1.9/SCN11A
CC (PubMed:14675784). {ECO:0000269|PubMed:14675784,
CC ECO:0000269|PubMed:26429937}.
CC -!- MISCELLANEOUS: Klint et al., 2015 worked with a recombinant peptide N-
CC terminally extended by an Ala residue. {ECO:0000305|PubMed:26429937}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 14 (Hntx-1)
CC subfamily. {ECO:0000305}.
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DR EMBL; GU292853; ADB56669.1; -; mRNA.
DR PDB; 1NIX; NMR; -; A=49-81.
DR PDB; 2MQF; NMR; -; A=48-81.
DR PDB; 2MXO; NMR; -; A=48-81.
DR PDBsum; 1NIX; -.
DR PDBsum; 2MQF; -.
DR PDBsum; 2MXO; -.
DR AlphaFoldDB; D2Y1X6; -.
DR BMRB; D2Y1X6; -.
DR SMR; D2Y1X6; -.
DR ArachnoServer; AS000338; mu-theraphotoxin-Hhn2b.
DR EvolutionaryTrace; D2Y1X6; -.
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; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..48
FT /evidence="ECO:0000305|PubMed:12727268,
FT ECO:0000305|PubMed:20192277"
FT /id="PRO_0000400495"
FT PEPTIDE 49..81
FT /note="Mu-theraphotoxin-Hhn2b 1"
FT /evidence="ECO:0000269|PubMed:12727268,
FT ECO:0000269|PubMed:20192277"
FT /id="PRO_0000045004"
FT MOD_RES 81
FT /note="Leucine amide"
FT /evidence="ECO:0000269|PubMed:14675784"
FT DISULFID 50..65
FT /evidence="ECO:0000269|PubMed:14675784,
FT ECO:0000269|PubMed:26429937, ECO:0007744|PDB:1NIX,
FT ECO:0007744|PDB:2MQF, ECO:0007744|PDB:2MXO"
FT DISULFID 57..70
FT /evidence="ECO:0000269|PubMed:14675784,
FT ECO:0000269|PubMed:26429937, ECO:0007744|PDB:1NIX,
FT ECO:0007744|PDB:2MQF, ECO:0007744|PDB:2MXO"
FT DISULFID 64..77
FT /evidence="ECO:0000269|PubMed:14675784,
FT ECO:0000269|PubMed:26429937, ECO:0007744|PDB:1NIX,
FT ECO:0007744|PDB:2MQF, ECO:0007744|PDB:2MXO"
FT MUTAGEN 51
FT /note="K->L: No gain of activity against hNav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:26429937"
FT MUTAGEN 54
FT /note="G->W: Low gain of inhibition activity against
FT hNav1.7/SCN9A (IC(50)=2.7 uM), and gain of binding to
FT anionic POPG liposome. Important gain of inhibition
FT activity (IC(50)=440 nM), and gain of binding to anionic
FT POPG liposome; when associated with S-71."
FT /evidence="ECO:0000269|PubMed:26429937"
FT MUTAGEN 71
FT /note="N->S: Low gain of inhibition activity against
FT hNav1.7/SCN9A (IC(50)=4.0 uM) and no change in binding to
FT anionic POPG liposome. Important gain of inhibition
FT activity (IC(50)=440 nM), and gain of binding to anionic
FT POPG liposome; when associated with W-54."
FT /evidence="ECO:0000269|PubMed:26429937"
FT MUTAGEN 79
FT /note="V->W: No gain of activity against hNav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:26429937"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:1NIX"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:1NIX"
FT STRAND 72..79
FT /evidence="ECO:0007829|PDB:1NIX"
SQ SEQUENCE 83 AA; 9240 MW; A72E5B88B0E04922 CRC64;
MKASMFLALA GLVLLFVVCY ASESEEKEFP RELISKIFAV DDFKGEEREC KGFGKSCVPG
KNECCSGYAC NSRDKWCKVL LGK
