TX15_GRARO
ID TX15_GRARO Reviewed; 82 AA.
AC P0DJA9; M5AYC6;
DT 14-DEC-2011, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 25-MAY-2022, entry version 27.
DE RecName: Full=Toxin GTx1-15 {ECO:0000250|UniProtKB:P0DL73, ECO:0000303|PubMed:21740921};
DE AltName: Full=Beta/omega-theraphotoxin-Gr2a {ECO:0000305};
DE Short=Beta/omega-TRTX-Gr2a {ECO:0000305};
DE AltName: Full=GpTx-1 {ECO:0000250|UniProtKB:P0DL72};
DE AltName: Full=GpTx-I {ECO:0000303|PubMed:29703751};
DE Flags: Precursor;
OS Grammostola rosea (Chilean rose tarantula) (Grammostola spatulata).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Grammostola.
OX NCBI_TaxID=432528;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 47-80, FUNCTION, MASS
RP SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=21740921; DOI=10.1016/j.toxicon.2011.06.006;
RA Ono S., Kimura T., Kubo T.;
RT "Characterization of voltage-dependent calcium channel blocking peptides
RT from the venom of the tarantula Grammostola rosea.";
RL Toxicon 58:265-276(2011).
RN [2]
RP FUNCTION, AND SYNTHESIS.
RX PubMed=29703751; DOI=10.1074/jbc.ra118.002553;
RA Agwa A.J., Peigneur S., Chow C.Y., Lawrence N., Craik D.J., Tytgat J.,
RA King G.F., Henriques S.T., Schroeder C.I.;
RT "Gating modifier toxins isolated from spider venom: modulation of voltage-
RT gated sodium channels and the role of lipid membranes.";
RL J. Biol. Chem. 293:9041-9052(2018).
CC -!- FUNCTION: Potent voltage-gated sodium channel blocker (By similarity).
CC Potently inhibits the voltage-gated sodium channels Nav1.7/SCN9A
CC (IC(50)=0.58-10 nM) (By similarity). Shows a moderate activity on
CC Nav1.1/SCN1A (IC(50)=6 nM), Nav1.2/SCN2A (IC(50)=5-128 nM),
CC Nav1.3/SCN3A (IC(50)=20.3-170 nM), and Nav1.6/SCN8A (IC(50)=17-20.1 nM)
CC (PubMed:29703751) (By similarity). Shows an unclear inhibition of
CC Nav1.4/SCN4A (IC(50)=200 nM to >10 uM), Nav1.5/SCN5A (IC(50)=140 nM to
CC >10 uM) and Nav1.8/SCN10A (IC(50)=68-12200 nM) (PubMed:29703751) (By
CC similarity). Weakly blocks the low voltage-gated calcium channels
CC Cav3.1/CACNA1G (30% inhibition of the peak current by 9.8 nM of the
CC toxin) (PubMed:21740921). It shows moderate affinity for lipid bilayers
CC (PubMed:29703751). {ECO:0000250|UniProtKB:P0DL72,
CC ECO:0000250|UniProtKB:P0DL73, ECO:0000269|PubMed:21740921,
CC ECO:0000269|PubMed:29703751}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21740921}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:21740921}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000250|UniProtKB:P0DL72}.
CC -!- DOMAIN: This toxin is amphipathic in nature with a hydrophobic face on
CC one side of the molecule (composed of residues 51-Phe-Met-52 and 73-
CC His--Phe-80) and a hydrophilic (mostly cationic) face on the opposite
CC side (composed of residues 56-Ile--Lys-61 and 64-Arg--Pro-65).
CC {ECO:0000250|UniProtKB:P0DL72}.
CC -!- MASS SPECTROMETRY: Mass=4071.21; Method=MALDI; Note=Monoisotopic mass
CC (after thiol reduction).; Evidence={ECO:0000269|PubMed:21740921};
CC -!- MISCELLANEOUS: The primary structure of the mature peptide is identical
CC to that of GpTx-1 from Grammostola porteri (AC P0DL72) and Gtx1-15 from
CC Paraphysa scrofa (AC P0DL73). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 08 (Gtx1-15)
CC subfamily. {ECO:0000305}.
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DR EMBL; AB201016; BAN13512.1; -; mRNA.
DR AlphaFoldDB; P0DJA9; -.
DR SMR; P0DJA9; -.
DR ArachnoServer; AS001910; omega-theraphotoxin-Gr2a.
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 InterPro; IPR013140; Huwentoxin_CS1.
DR Pfam; PF07740; Toxin_12; 1.
DR PROSITE; PS60021; HWTX_1; 1.
PE 1: Evidence at protein level;
KW Amidation; Calcium channel impairing toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin; Secreted;
KW Signal; Toxin; Voltage-gated calcium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..46
FT /evidence="ECO:0000269|PubMed:21740921"
FT /id="PRO_0000414299"
FT PEPTIDE 47..80
FT /note="Toxin GTx1-15"
FT /evidence="ECO:0000269|PubMed:21740921"
FT /id="PRO_0000414300"
FT MOD_RES 80
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000250|UniProtKB:P0DL72,
FT ECO:0000250|UniProtKB:P0DL73"
FT DISULFID 48..63
FT /evidence="ECO:0000250|UniProtKB:P83471"
FT DISULFID 55..69
FT /evidence="ECO:0000250|UniProtKB:P83471"
FT DISULFID 62..76
FT /evidence="ECO:0000250|UniProtKB:P83471"
SQ SEQUENCE 82 AA; 9364 MW; 7C9A0312D0FB651C CRC64;
MKTSVVFVIA GLALLSVACY ASELKEQSSI NEVLSTIFHF EQPEERDCLG FMRKCIPDND
KCCRPNLVCS RTHKWCKYVF GK
