VSTX1_GRARO
ID VSTX1_GRARO Reviewed; 63 AA.
AC P60980; M5AY63;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 09-DEC-2015, sequence version 2.
DT 25-MAY-2022, entry version 70.
DE RecName: Full=Kappa-theraphotoxin-Gr3a;
DE Short=Kappa-TRTX-Gr3a;
DE AltName: Full=Voltage sensor toxin 1;
DE Short=VsTx1 {ECO:0000303|PubMed:19955179};
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].
RC TISSUE=Venom gland;
RA Kimura T., Kubo T.;
RT "Grammostola spatulata venom gland cDNA.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 30-63, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=12629550; DOI=10.1038/nature01473;
RA Ruta V., Jiang Y., Lee A., Chen J., MacKinnon R.;
RT "Functional analysis of an archaebacterial voltage-dependent K+ channel.";
RL Nature 422:180-185(2003).
RN [3]
RP PROTEIN SEQUENCE OF 30-63, MASS SPECTROMETRY, FUNCTION, AND TOXIN TARGET.
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 [4]
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 [5]
RP FUNCTION.
RX PubMed=15241419; DOI=10.1038/nature02632;
RA Lee S.-Y., MacKinnon R.;
RT "A membrane-access mechanism of ion channel inhibition by voltage sensor
RT toxins from spider venom.";
RL Nature 430:232-235(2004).
RN [6]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=15287735; DOI=10.1021/bi049463y;
RA Ruta V., MacKinnon R.;
RT "Localization of the voltage-sensor toxin receptor on KvAP.";
RL Biochemistry 43:10071-10079(2004).
RN [7]
RP FUNCTION.
RX PubMed=17002285; DOI=10.1021/bi061111z;
RA Bemporad D., Sands Z.A., Wee C.L., Grottesi A., Sansom M.S.;
RT "Vstx1, a modifier of Kv channel gating, localizes to the interfacial
RT region of lipid bilayers.";
RL Biochemistry 45:11844-11855(2006).
RN [8]
RP STRUCTURE BY NMR OF 30-63, DISULFIDE BONDS, MEMBRANE-PARTITIONING, AND
RP SYNTHESIS.
RX PubMed=15835890; DOI=10.1021/bi0477034;
RA Jung H.J., Lee J.Y., Kim S.H., Eu Y.-J., Shin S.Y., Milescu M.,
RA Swartz K.J., Kim J.I.;
RT "Solution structure and lipid membrane partitioning of VSTx1, an inhibitor
RT of the KvAP potassium channel.";
RL Biochemistry 44:6015-6023(2005).
CC -!- FUNCTION: Inhibits sodium channels Nav1.7/SCN9A and potassium channels
CC Kv11.1/KCNH2. Also binds the voltage-sensor domain of the potassium
CC channel KvAP (from the archaeon Aeropyrum pernix) with very slow
CC apparent binding kinetics and affects channel gating. Reaches its
CC target by dynamically partitioning into anionic or zwitterionic
CC headgroup lipid membranes. May bind to the open state of KvAP.
CC {ECO:0000269|PubMed:15241419, ECO:0000269|PubMed:15287735,
CC ECO:0000269|PubMed:17002285, ECO:0000269|PubMed:19955179}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC -!- MASS SPECTROMETRY: Mass=3997.0; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:19955179};
CC -!- MISCELLANEOUS: Does not inhibit potassium channels Kv1.1/KCNA1
CC (IC(50)>200 uM), Kv1.4/KCNA4 (IC(50)>200 uM), Kv11.2/KCNH6 (IC(50)=45
CC uM) and Kv11.3/KCNH7 (IC(50)=55 uM) and sodium channels Nav1.1/SCN1A,
CC Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.4/SCN4A, Nav1.5/SCN5A, Nav1.6/SCN8A.
CC {ECO:0000305|PubMed:19955179}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 63 (VsTx1)
CC subfamily. {ECO:0000305}.
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DR EMBL; AB200994; BAN13490.1; -; mRNA.
DR PDB; 1S6X; NMR; -; A=30-63.
DR PDB; 2N1N; NMR; -; A=30-63.
DR PDBsum; 1S6X; -.
DR PDBsum; 2N1N; -.
DR AlphaFoldDB; P60980; -.
DR SMR; P60980; -.
DR TCDB; 8.B.5.3.8; the na(+)/k(+)/ca(2+) channel targeting tarantula huwentoxin (tht) family.
DR ArachnoServer; AS000423; kappa-theraphotoxin-Gr3a.
DR EvolutionaryTrace; P60980; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
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.
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 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Neurotoxin;
KW Potassium channel impairing toxin; Secreted; Signal; Toxin;
KW Voltage-gated potassium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..29
FT /evidence="ECO:0000305"
FT /id="PRO_0000434821"
FT PEPTIDE 30..63
FT /note="Kappa-theraphotoxin-Gr3a"
FT /id="PRO_0000045008"
FT DISULFID 31..45
FT /evidence="ECO:0000269|PubMed:15835890"
FT DISULFID 38..50
FT /evidence="ECO:0000269|PubMed:15835890"
FT DISULFID 44..57
FT /evidence="ECO:0000269|PubMed:15835890"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:1S6X"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:1S6X"
FT TURN 52..55
FT /evidence="ECO:0007829|PDB:1S6X"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:1S6X"
SQ SEQUENCE 63 AA; 7175 MW; 931A386CF4122268 CRC64;
MKTSVFVLVL GLVLLFAVSF ATEMEESARE CGKFMWKCKN SNDCCKDLVC SSRWKWCVLA
SPF
