TX3A_HETMC
ID TX3A_HETMC Reviewed; 37 AA.
AC C0HKD0;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2017, sequence version 1.
DT 25-MAY-2022, entry version 11.
DE RecName: Full=Pi-theraphotoxin-Hm3a {ECO:0000303|PubMed:28327374};
DE Short=Pi-TRTX-Hm3a {ECO:0000303|PubMed:28327374};
OS Heteroscodra maculata (Togo starburst tarantula) (Togo starburst baboon
OS spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Heteroscodra.
OX NCBI_TaxID=268413;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY,
RP MUTAGENESIS OF VAL-37, AND STABILITY.
RC TISSUE=Venom;
RX PubMed=28327374; DOI=10.1016/j.neuropharm.2017.03.020;
RA Er S.Y., Cristofori-Armstrong B., Escoubas P., Rash L.D.;
RT "Discovery and molecular interaction studies of a highly stable, tarantula
RT peptide modulator of acid-sensing ion channel 1.";
RL Neuropharmacology 114:3750-3755(2017).
CC -!- FUNCTION: This toxin acts on different isoforms of acid-sensing ion
CC channel ASIC1 in a similar manner to psalmotoxin-1 (AC P60514). On
CC ASIC1a homotrimer, it provokes a pH-dependent inhibition (IC(50)=39.7
CC nM on human and IC(50)=1.3 nM on rat channels), whereas it potentiates
CC ASIC1b homotrimer and ASIC1a-ASIC1b heterotrimer (EC(50)=178.1 nM on
CC human ASIC1b, EC(50)=46.5 nM on rat ASIC1b and EC(50)=17.4 nM on rat
CC ASIC1a-ASIC1b channels). On rat ASIC1a, it acts by inhibiting channel
CC currents by shifting the pH of half-maximal effect (pH(50)) of steady-
CC state desensitization and activation to more alkaline values.
CC {ECO:0000269|PubMed:28327374}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28327374}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:28327374}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin. {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=4285.05; Method=MALDI; Note=Monoisotopic mass.;
CC Evidence={ECO:0000269|PubMed:28327374};
CC -!- MISCELLANEOUS: This toxin if more stable than psalmotoxin-1 (AC P60514)
CC when challenged with either high temperature or human serum.
CC {ECO:0000269|PubMed:28327374}.
CC -!- MISCELLANEOUS: Does not show activity on Nav1.2/SCN2A,
CC Kv10.1/KCNH1/EAG1 and Kv11.1/KCNH2/ERG1. {ECO:0000269|PubMed:28327374}.
CC -!- SIMILARITY: Belongs to the psalmotoxin-1 family. {ECO:0000305}.
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DR AlphaFoldDB; C0HKD0; -.
DR SMR; C0HKD0; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Knottin; Neurotoxin; Proton-gated sodium channel impairing toxin; Secreted;
KW Toxin.
FT PEPTIDE 1..37
FT /note="Pi-theraphotoxin-Hm3a"
FT /evidence="ECO:0000269|PubMed:28327374"
FT /id="PRO_0000439456"
FT DISULFID 3..18
FT /evidence="ECO:0000250|UniProtKB:P60514"
FT DISULFID 10..23
FT /evidence="ECO:0000250|UniProtKB:P60514"
FT DISULFID 17..33
FT /evidence="ECO:0000250|UniProtKB:P60514"
FT MUTAGEN 37
FT /note="V->VP: 3.3-fold increase in ability to inhibit
FT rASIC1a."
FT /evidence="ECO:0000269|PubMed:28327374"
SQ SEQUENCE 37 AA; 4293 MW; 2A1DE32844095916 CRC64;
EPCIPKWKSC VNRHGDCCAG LECWKRRKSF EVCVPKV
