TX1_GRARO
ID TX1_GRARO Reviewed; 29 AA.
AC P85117;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 1.
DT 25-MAY-2022, entry version 42.
DE RecName: Full=Beta-theraphotoxin-Gr1a {ECO:0000305};
DE Short=Beta-TRTX-Gr1a {ECO:0000305};
DE AltName: Full=GrTx1 {ECO:0000303|PubMed:19955179};
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 PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=17418351; DOI=10.1016/j.toxicon.2007.02.015;
RA Clement H., Odell G., Zamudio F.Z., Redaelli E., Wanke E., Alagon A.,
RA Possani L.D.;
RT "Isolation and characterization of a novel toxin from the venom of the
RT spider Grammostola rosea that blocks sodium channels.";
RL Toxicon 50:65-74(2007).
RN [2]
RP FUNCTION.
RX PubMed=19955179; DOI=10.1074/jbc.m109.054718;
RA Redaelli E., Cassulini R.R., Silva D.F., Clement H., Schiavon E.,
RA Zamudio F.Z., Odell G., Arcangeli A., Clare J.J., Alagon A.,
RA de la Vega R.C., Possani L.D., Wanke E.;
RT "Target promiscuity and heterogeneous effects of tarantula venom peptides
RT affecting Na+ and K+ ion channels.";
RL J. Biol. Chem. 285:4130-4142(2010).
RN [3]
RP ERRATUM OF PUBMED:19955179.
RA Redaelli E., Cassulini R.R., Silva D.F., Clement H., Schiavon E.,
RA Zamudio F.Z., Odell G., Arcangeli A., Clare J.J., Alagon A.,
RA de la Vega R.C., Possani L.D., Wanke E.;
RL J. Biol. Chem. 285:13314-13314(2010).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF GLN-22.
RX PubMed=30661758; DOI=10.1016/j.cell.2018.12.018;
RA Xu H., Li T., Rohou A., Arthur C.P., Tzakoniati F., Wong E., Estevez A.,
RA Kugel C., Franke Y., Chen J., Ciferri C., Hackos D.H., Koth C.M.,
RA Payandeh J.;
RT "Structural basis of Nav1.7 inhibition by a gating-modifier spider toxin.";
RL Cell 176:702-715(2019).
RN [5]
RP FUNCTION ON NAV1.7/SCN9A, AND SYNTHESIS.
RX PubMed=31234412; DOI=10.3390/toxins11060367;
RA Nicolas S., Zoukimian C., Bosmans F., Montnach J., Diochot S., Cuypers E.,
RA De Waard S., Beroud R., Mebs D., Craik D., Boturyn D., Lazdunski M.,
RA Tytgat J., De Waard M.;
RT "Chemical synthesis, proper folding, Nav channel selectivity profile and
RT analgesic properties of the spider peptide Phlotoxin 1.";
RL Toxins 11:0-0(2019).
CC -!- FUNCTION: Inhibits voltage-gated sodium channels Nav1.1/SCN1A
CC (IC(50)=630 nM), Nav1.2/SCN2A (IC(50)=230 nM), Nav1.3/SCN3A (IC(50)=770
CC nM), Nav1.4/SCN4A (IC(50)=1290 nM), Nav1.6/SCN8A (IC(50)=630 nM),
CC Nav1.7/SCN9A (IC(50)=15.3-1000 nM) and potassium channels Kv11.1/KCNH2
CC (IC(50)=4.2 uM). {ECO:0000269|PubMed:17418351,
CC ECO:0000269|PubMed:19955179, ECO:0000269|PubMed:30661758,
CC ECO:0000269|PubMed:31234412}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17418351}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:17418351}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000250|UniProtKB:P83476}.
CC -!- MASS SPECTROMETRY: Mass=3697; Mass_error=1; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:17418351};
CC -!- MISCELLANEOUS: This toxin does not inhibit sodium channels Nav1.5/SCN5A
CC (IC(50)=22 uM) and potassium channels Kv11.2/KCNH6, Kv11.3/KCNH7,
CC Kv1.1/KCNA1 and Kv1.4/KCNA4 (IC(50)>200 uM).
CC {ECO:0000269|PubMed:19955179}.
CC -!- SIMILARITY: Belongs to the neurotoxin 30 (phrixotoxin) family.
CC {ECO:0000305}.
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DR AlphaFoldDB; P85117; -.
DR SMR; P85117; -.
DR ArachnoServer; AS000223; beta-theraphotoxin-Gr1a.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0017080; F:sodium 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; Potassium channel impairing toxin; Secreted; Toxin;
KW Voltage-gated potassium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT PEPTIDE 1..29
FT /note="Beta-theraphotoxin-Gr1a"
FT /evidence="ECO:0000303|PubMed:17418351"
FT /id="PRO_0000284758"
FT DISULFID 2..16
FT /evidence="ECO:0000250|UniProtKB:P83476"
FT DISULFID 9..21
FT /evidence="ECO:0000250|UniProtKB:P83476"
FT DISULFID 15..25
FT /evidence="ECO:0000250|UniProtKB:P83476"
FT MUTAGEN 22
FT /note="Q->D: 8-fold decrease in inhibitory potency on human
FT Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:30661758"
FT MUTAGEN 22
FT /note="Q->E: 9-fold decrease in inhibitory potency on human
FT Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:30661758"
FT MUTAGEN 22
FT /note="Q->K: 111-fold increase in inhibitory potency on
FT human Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:30661758"
FT MUTAGEN 22
FT /note="Q->R: 100-fold increase in inhibitory potency on
FT human Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:30661758"
SQ SEQUENCE 29 AA; 3703 MW; 93E9F690431B9B34 CRC64;
YCQKWMWTCD SKRKCCEDMV CQLWCKKRL
