ID H1A02_CYRHA Reviewed; 83 AA. AC D2Y1X7; P83591; DT 02-NOV-2010, integrated into UniProtKB/Swiss-Prot. DT 02-MAR-2010, sequence version 1. DT 02-JUN-2021, entry version 29. DE RecName: Full=Mu-theraphotoxin-Hhn2b 2 {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. 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 CC (AECKGFGKSCVPGKNECCSGYACNSRDKWCKVLL). {ECO:0000305|PubMed:26429937}. CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 14 (Hntx-1) CC subfamily. {ECO:0000305}. 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 EMBL; GU292854; ADB56670.1; -; mRNA. DR BMRB; D2Y1X7; -. DR SMR; D2Y1X7; -. DR ArachnoServer; AS000338; mu-theraphotoxin-Hhn2b. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro. DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW. DR GO; GO:0009405; P:pathogenesis; IEA:InterPro. 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 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_0000400496" FT PEPTIDE 49..81 FT /note="Mu-theraphotoxin-Hhn2b 2" FT /evidence="ECO:0000269|PubMed:12727268, FT ECO:0000269|PubMed:20192277" FT /id="PRO_0000400497" 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" FT DISULFID 57..70 FT /evidence="ECO:0000269|PubMed:14675784, FT ECO:0000269|PubMed:26429937" FT DISULFID 64..77 FT /evidence="ECO:0000269|PubMed:14675784, FT ECO:0000269|PubMed:26429937" 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" SQ SEQUENCE 83 AA; 9270 MW; A72E5B88A1E04933 CRC64; MKASMFLALA GLVLLFVVCY ASESEEKEFP RELISKIFTV DDFKGEEREC KGFGKSCVPG KNECCSGYAC NSRDKWCKVL LGK //