TAP2A_THEAO
ID TAP2A_THEAO Reviewed; 33 AA.
AC P0DQO4;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 1.
DT 25-MAY-2022, entry version 6.
DE RecName: Full=Mu/omega-theraphotoxin-Tap2a {ECO:0000303|PubMed:32826759};
DE Short=Mu/omega-TRTX-Tap2a {ECO:0000303|PubMed:32826759};
OS Theraphosa apophysis (Goliath pinkfoot tarantula) (Pseudotheraphosa
OS apophysis).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Theraphosa.
OX NCBI_TaxID=1956358;
RN [1]
RP PROTEIN SEQUENCE, SUBCELLULAR LOCATION, 3D-STRUCTURE MODELING, RECOMBINANT
RP EXPRESSION, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=32826759; DOI=10.1097/j.pain.0000000000002041;
RA Cardoso F.C., Castro J., Grundy L., Schober G., Garcia-Caraballo S.,
RA Zhao T., Herzig V., King G.F., Brierley S.M., Lewis R.J.;
RT "A spider-venom peptide with multi-target activity on sodium and calcium
RT channels alleviates chronic visceral pain in a model of irritable bowel
RT syndrome.";
RL Pain 162:569-581(2021).
CC -!- FUNCTION: Gating-modifier toxin that inhibits both sodium (Nav) and
CC calcium (Cav3) channels by inducing hyperpolarizing shift in voltage-
CC dependence of activation and steady state inactivation. Inhibits
CC Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.6/SCN6A, Nav1.7/SCN9A and
CC Cav3.1/CACNA1G sodium and calcium channels at nanomolar concentrations
CC (IC(50)=169-621 nM). Surprisingly, selectively slows fast inactivation
CC of Nav1.3/SCN3A. Also shows moderate inhibition of Nav1.3/SCN3A sodium
CC channels (IC(50)=1216 nM). {ECO:0000269|PubMed:32826759}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:32826759}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:32826759}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000250|UniProtKB:P58426}.
CC -!- MASS SPECTROMETRY: Mass=3843.4; Method=MALDI; Note=Monoisotopic mass.;
CC Evidence={ECO:0000269|PubMed:32826759};
CC -!- MISCELLANEOUS: Shows no or weak activity on Nav1.4/SCN4A and
CC Nav1.5/SCN5A sodium channels, as well as on Cav3.2/CACNA1H and
CC Cav3.3/CACNA1I calcium channels. {ECO:0000269|PubMed:32826759}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 59 (Tltx)
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 AlphaFoldDB; P0DQO4; -.
DR SMR; P0DQO4; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
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 Pfam; PF07740; Toxin_12; 1.
PE 1: Evidence at protein level;
KW Calcium channel impairing toxin; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Secreted; Toxin;
KW Voltage-gated calcium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..33
FT /note="Mu/omega-theraphotoxin-Tap2a"
FT /evidence="ECO:0000269|PubMed:32826759"
FT /id="PRO_0000451750"
FT DISULFID 2..17
FT /evidence="ECO:0000250|UniProtKB:P58426"
FT DISULFID 9..22
FT /evidence="ECO:0000250|UniProtKB:P58426"
FT DISULFID 16..29
FT /evidence="ECO:0000250|UniProtKB:P58426"
SQ SEQUENCE 33 AA; 3852 MW; 610950EC43B955C4 CRC64;
DCLGFMKPCD INNDKCCSSY VCGRNNHWCK FHL