AF2_GRARO
ID AF2_GRARO Reviewed; 81 AA.
AC P61409; F8WQV7; M5AYD2;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 2.
DT 25-MAY-2022, entry version 50.
DE RecName: Full=Kappa-theraphotoxin-Gr2c {ECO:0000303|PubMed:31234412};
DE Short=Kappa-TRTX-Gr2c {ECO:0000303|PubMed:31234412};
DE AltName: Full=GTx2-1-1 {ECO:0000312|EMBL:BAN13517.1};
DE AltName: Full=GsAF II {ECO:0000303|Ref.2};
DE Short=GsAFII {ECO:0000303|PubMed:19955179, ECO:0000303|PubMed:21740921};
DE AltName: Full=GsAf2 {ECO:0000303|PubMed:30661758};
DE AltName: Full=Mechanotoxin-alpha;
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 51-81, SUBCELLULAR
RP LOCATION, AND 3D-STRUCTURE MODELING.
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 PROTEIN SEQUENCE OF 51-81, FUNCTION, SUBCELLULAR LOCATION, AND MASS
RP SPECTROMETRY.
RC TISSUE=Venom;
RA Lampe R.A.;
RT "Analgesic peptides from venom of Grammostola spatulata and use thereof.";
RL Patent number US5877026, 02-MAR-1999.
RN [3]
RP PROTEIN SEQUENCE OF 51-81, FUNCTION, SUBCELLULAR LOCATION, AND MASS
RP SPECTROMETRY.
RC TISSUE=Venom;
RA Lampe R.A.;
RT "Antiarrhythmic peptide from venom of spider Grammostola spatulata.";
RL Patent number US5968838, 19-OCT-1999.
RN [4]
RP PROTEIN SEQUENCE OF 51-81, MASS SPECTROMETRY, AND 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 [5]
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 [6]
RP FUNCTION.
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 [7]
RP FUNCTION ON NAV1.7/SCN9A, AND SYNTHESIS OF 51-81.
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 sodium channels Nav1.1/SCN1A (IC(50)=5.7 uM),
CC Nav1.2/SCN2A (IC(50)=12 uM), Nav1.4/SCN4A (IC(50)=4 uM), Nav1.6/SCN8A
CC (IC(50)=6.6 uM), Nav1.7/SCN9A (IC(50)=13.6-1030 nM), potassium channels
CC Kv11.1/KCNH2 (IC(50)=4.7 uM), as well as high-voltage-gated calcium
CC channels Cav1.2/CACNA1C (IC(50)= nM) (PubMed:19955179, PubMed:30661758,
CC PubMed:31234412). Also blocks mechanosensitive ion channels (also named
CC stretch-activated channels or SACs) and the hypotonic cell swelling
CC induced calcium increase associated with the activation of such
CC channels (Ref.3). It can thus be useful in treating cardiac ventricular
CC disturbances (Ref.3). Also induces analgesia in mammals (Ref.2).
CC {ECO:0000269|PubMed:19955179, ECO:0000269|PubMed:30661758,
CC ECO:0000269|PubMed:31234412, ECO:0000269|Ref.2, ECO:0000269|Ref.3}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21740921,
CC ECO:0000269|Ref.2, ECO:0000269|Ref.3}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:21740921, ECO:0000305|Ref.2, ECO:0000305|Ref.3}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000250|UniProtKB:P61230}.
CC -!- MASS SPECTROMETRY: Mass=3979.9; Method=Electrospray;
CC Evidence={ECO:0000269|Ref.2, ECO:0000269|Ref.3};
CC -!- MASS SPECTROMETRY: Mass=3980.0; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:19955179};
CC -!- MISCELLANEOUS: This toxin does not have effect on sodium channels
CC Nav1.3/SCN3A (IC(50)=24 uM) and Nav1.5/SCN5A (IC(50)>40 uM), and
CC potassium channels Kv1.1/KCNA1, Kv1.4/KCNA4, Kv11.2/KCNH6 and
CC Kv11.3/KCNH7 (IC(50)>200 uM). {ECO:0000305|PubMed:19955179}.
CC -!- SIMILARITY: Belongs to the neurotoxin 30 (phrixotoxin) family.
CC {ECO:0000305}.
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DR EMBL; AB201021; BAN13517.1; -; mRNA.
DR EMBL; AB612242; BAK55734.1; -; mRNA.
DR AlphaFoldDB; P61409; -.
DR SMR; P61409; -.
DR ArachnoServer; AS000027; kappa-theraphotoxin-Gr2c.
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: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 Calcium channel impairing toxin; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Potassium channel impairing toxin;
KW Secreted; Signal; Toxin; Voltage-gated calcium channel impairing toxin;
KW Voltage-gated potassium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..50
FT /evidence="ECO:0000269|PubMed:19955179,
FT ECO:0000269|PubMed:21740921, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.3"
FT /id="PRO_0000414298"
FT PEPTIDE 51..81
FT /note="Kappa-theraphotoxin-Gr2c"
FT /evidence="ECO:0000269|PubMed:21740921"
FT /id="PRO_0000045016"
FT DISULFID 52..66
FT /evidence="ECO:0000250|UniProtKB:P61230"
FT DISULFID 59..71
FT /evidence="ECO:0000250|UniProtKB:P61230"
FT DISULFID 65..75
FT /evidence="ECO:0000250|UniProtKB:P61230"
FT CONFLICT 81
FT /note="Missing (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 81 AA; 9679 MW; 8BD59C517DAA704C CRC64;
MKAFFVILGL ALLCAYSFAL EEQDQLSLRN DLLTVMFAEN SELTPETEER YCQKWMWTCD
EERKCCEGLV CRLWCKKKIE W
