ID   TXH3_CYRSC              Reviewed;          87 AA.
AC   P61103;
DT   26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 2.
DT   25-MAY-2022, entry version 68.
DE   RecName: Full=Mu-theraphotoxin-Hs1a;
DE            Short=Mu-TRTX-Hs1a;
DE   AltName: Full=Huwentoxin-3;
DE   AltName: Full=Huwentoxin-III {ECO:0000303|PubMed:14614533};
DE            Short=HwTx-III {ECO:0000303|PubMed:14614533};
DE   Contains:
DE     RecName: Full=U2-theraphotoxin-Hs1b;
DE              Short=U2-TRTX-Hs1b;
DE     AltName: Full=HWTX-IIIa;
DE     AltName: Full=Mutant of huwentoxin-3;
DE     AltName: Full=Mutant of huwentoxin-III;
DE              Short=mHWTX-III;
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   PROTEIN SEQUENCE OF 53-85, FUNCTION, DISULFIDE BONDS, TOXIC DOSE, MASS
RP   SPECTROMETRY, DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=14614533;
RA   Huang R.-H., Liu Z.-H., Liang S.-P.;
RT   "Purification and characterization of a neurotoxic peptide huwentoxin-III
RT   and a natural inactive mutant from the venom of the spider Selenocosmia
RT   huwena Wang (Ornithoctonus huwena Wang).";
RL   Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 35:976-980(2003).
RN   [3]
RP   FUNCTION.
RX   PubMed=20506577; DOI=10.1631/jzus.b0900393;
RA   Wang R.L., Yi S., Liang S.P.;
RT   "Mechanism of action of two insect toxins huwentoxin-III and hainantoxin-VI
RT   on voltage-gated sodium channels.";
RL   J. Zhejiang Univ. Sci. B 11:451-457(2010).
CC   -!- FUNCTION: [Mu-theraphotoxin-Hs1a]: Probable sodium channel pore blocker
CC       that dose-dependently inhibits voltage-gated sodium channels (VGSC) on
CC       DUM neurons in a way similar to tetrodotoxin (PubMed:20506577). Has no
CC       effect on the kinetics of activation and inactivation
CC       (PubMed:20506577). Seems not to interact with VGSC in an inactivated
CC       state (PubMed:20506577). In vivo, reversibly paralyzes cockroaches, and
CC       can enhance the muscular contraction elicited by stimulating its nerve
CC       (PubMed:14614533). {ECO:0000269|PubMed:14614533,
CC       ECO:0000269|PubMed:20506577}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14614533}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin. {ECO:0000250}.
CC   -!- MASS SPECTROMETRY: [Mu-theraphotoxin-Hs1a]: Mass=3853.35; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:14614533};
CC   -!- MASS SPECTROMETRY: [U2-theraphotoxin-Hs1b]: Mass=3667.40; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:14614533};
CC   -!- DISRUPTION PHENOTYPE: The natural mutant mHwTx-III does not reversibly
CC       paralyze cockroaches. {ECO:0000269|PubMed:14614533}.
CC   -!- TOXIC DOSE: PD(50) of HwTx-III is 192.95 +/- 120.84 mg/kg to locusts.
CC       {ECO:0000269|PubMed:14614533}.
CC   -!- MISCELLANEOUS: Does not inhibit sodium channels of adult rat DRG
CC       neurons (PubMed:20506577). Neither HwTx-III, nor mHwTx-III agglutinate
CC       erythrocytes (PubMed:14614533). {ECO:0000269|PubMed:14614533,
CC       ECO:0000269|PubMed:20506577}.
CC   -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 51 (Hntx-8)
CC       subfamily. Hntx-8 sub-subfamily. {ECO:0000305}.
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DR   AlphaFoldDB; P61103; -.
DR   SMR; P61103; -.
DR   ArachnoServer; AS000331; mu-theraphotoxin-Hs1a.
DR   ArachnoServer; AS000754; U2-theraphotoxin-Hs1b.
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   Cleavage on pair of basic residues; Direct protein sequencing;
KW   Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin; Secreted;
KW   Signal; Toxin; Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   PROPEP          25..52
FT                   /evidence="ECO:0000269|PubMed:14614533"
FT                   /id="PRO_0000035564"
FT   CHAIN           53..85
FT                   /note="Mu-theraphotoxin-Hs1a"
FT                   /evidence="ECO:0000269|PubMed:14614533"
FT                   /id="PRO_0000035565"
FT   CHAIN           53..84
FT                   /note="U2-theraphotoxin-Hs1b"
FT                   /id="PRO_0000035566"
FT   DISULFID        54..67
FT                   /evidence="ECO:0000250|UniProtKB:B3FIS6"
FT   DISULFID        61..72
FT                   /evidence="ECO:0000250|UniProtKB:B3FIS6"
FT   DISULFID        66..79
FT                   /evidence="ECO:0000250|UniProtKB:B3FIS6"
SQ   SEQUENCE   87 AA;  10155 MW;  E9ABB859D99BB8FE CRC64;
     MVNMKASMFL TFAGLVLLFV VCYASESEEK EFPKEMLSSI FAVDNDFKQE ERDCAGYMRE
     CKEKLCCSGY VCSSRWKWCV LPAPWRR