TX1_STRGF
ID TX1_STRGF Reviewed; 34 AA.
AC P56855;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 87.
DE RecName: Full=Kappa-theraphotoxin-Scg1a {ECO:0000305};
DE Short=Kappa-TRTX-Scg1a {ECO:0000305};
DE AltName: Full=SGTx1 {ECO:0000303|PubMed:10504388, ECO:0000303|PubMed:11312507, ECO:0000303|PubMed:14744131, ECO:0000303|PubMed:17071657};
DE Short=SGTx {ECO:0000303|PubMed:15051809, ECO:0000303|PubMed:20643084};
DE AltName: Full=SgTx-I {ECO:0000303|PubMed:29703751};
OS Stromatopelma calceatum griseipes (Feather leg baboon tarantula) (Scodra
OS griseipes).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Stromatopelma.
OX NCBI_TaxID=118974;
RN [1]
RP PROTEIN SEQUENCE, SUBCELLULAR LOCATION, FUNCTION, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=10504388; DOI=10.1046/j.1432-1327.1999.00726.x;
RA Marvin L., De E., Cosette P., Gagnon J., Molle G., Lange C.;
RT "Isolation, amino acid sequence and functional assays of SGTx1. The first
RT toxin purified from the venom of the spider Scodra griseipes.";
RL Eur. J. Biochem. 265:572-579(1999).
RN [2]
RP MASS SPECTROMETRY.
RX PubMed=11312507; DOI=10.1002/rcm.261;
RA Marvin L., Lange C.;
RT "Conformational study of a new SGTx1 neurotoxin from the spider Scodra
RT griseipes using mass spectrometry.";
RL Rapid Commun. Mass Spectrom. 15:579-585(2001).
RN [3]
RP FUNCTION, MUTAGENESIS OF THR-1; ARG-3; TYR-4; LEU-5; PHE-6; GLY-7; GLY-8;
RP LYS-10; THR-11; THR-12; ALA-13; ASP-14; LYS-17; HIS-18; ALA-20; ARG-22;
RP SER-23; ASP-24; GLY-25; LYS-26; ALA-29; TRP-30; ASP-31; GLY-32; THR-33 AND
RP PHE-34, SYNTHESIS, AND IDENTIFICATION OF THE ACTIVE FACE.
RX PubMed=15051809; DOI=10.1085/jgp.200309005;
RA Wang J.M., Roh S.H., Kim S., Lee C.W., Kim J.I., Swartz K.J.;
RT "Molecular surface of tarantula toxins interacting with voltage sensors in
RT K(v) channels.";
RL J. Gen. Physiol. 123:455-467(2004).
RN [4]
RP MEMBRANE-PARTITIONING.
RX PubMed=17071657; DOI=10.1529/biophysj.106.098681;
RA Wee C.L., Bemporad D., Sands Z.A., Gavaghan D., Sansom M.S.;
RT "SGTx1, a Kv channel gating-modifier toxin, binds to the interfacial region
RT of lipid bilayers.";
RL Biophys. J. 92:7-9(2007).
RN [5]
RP MEMBRANE-PARTITIONING, SITES ARG-3; LEU-5; PHE-6; ARG-22 AND TRP-30, AND
RP SYNTHESIS.
RX PubMed=20643084; DOI=10.1016/j.bpj.2010.04.061;
RA Jung H.H., Jung H.J., Milescu M., Lee C.W., Lee S., Lee J.Y., Eu Y.-J.,
RA Kim H.H., Swartz K.J., Kim J.I.;
RT "Structure and orientation of a voltage-sensor toxin in lipid membranes.";
RL Biophys. J. 99:638-646(2010).
RN [6]
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).
RN [7]
RP STRUCTURE BY NMR, SYNTHESIS, DISULFIDE BONDS, AND FUNCTION.
RX PubMed=14744131; DOI=10.1021/bi0353373;
RA Lee C.W., Kim S., Roh S.H., Endoh H., Kodera Y., Maeda T., Kohno T.,
RA Wang J.M., Swartz K.J., Kim J.I.;
RT "Solution structure and functional characterization of SGTx1, a modifier of
RT Kv2.1 channel gating.";
RL Biochemistry 43:890-897(2004).
CC -!- FUNCTION: Reversibly inhibits potassium currents in oocytes expressing
CC Kv2.1/KCNB1 channels (Kd=2.7 uM) (PubMed:15051809). Acts by shifting
CC activation of the channel to more depolarized voltages. The toxin may
CC bind to the S3b-S4 helices of the voltage sensor paddle. One, two,
CC three or four toxin molecules may bind the Kv2.1/KCNB1 channel. It
CC shows low to moderate affinity for lipid bilayers (PubMed:29703751). It
CC partitions into the bilayer membrane, where it stabilizes at the
CC water/membrane interface (PubMed:17071657, PubMed:20643084).
CC {ECO:0000269|PubMed:10504388, ECO:0000269|PubMed:14744131,
CC ECO:0000269|PubMed:15051809, ECO:0000269|PubMed:17071657,
CC ECO:0000269|PubMed:20643084, ECO:0000269|PubMed:29703751}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10504388}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:10504388}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:14744131}.
CC -!- MASS SPECTROMETRY: Mass=3775.7; Mass_error=0.6; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:10504388};
CC -!- MASS SPECTROMETRY: Mass=3776.7; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:11312507};
CC -!- MISCELLANEOUS: Shows no or very low activity on Nav1.2/SCN2A,
CC Nav1.4/SCN4A, Nav1.5/SCN5A, Nav1.6/SCN8A, and Nav1.7/SCN9A (IC(50)>3
CC uM). {ECO:0000269|PubMed:29703751}.
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 09 (HaTx)
CC subfamily. {ECO:0000305}.
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DR PDB; 1LA4; NMR; -; A=1-34.
DR PDBsum; 1LA4; -.
DR AlphaFoldDB; P56855; -.
DR SMR; P56855; -.
DR IntAct; P56855; 1.
DR ArachnoServer; AS000227; kappa-theraphotoxin-Scg1a.
DR EvolutionaryTrace; P56855; -.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
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: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 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Neurotoxin;
KW Potassium channel impairing toxin; Secreted; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT PEPTIDE 1..34
FT /note="Kappa-theraphotoxin-Scg1a"
FT /evidence="ECO:0000269|PubMed:10504388"
FT /id="PRO_0000045024"
FT REGION 4..6
FT /note="Involved in active face"
FT /evidence="ECO:0000269|PubMed:15051809"
FT SITE 3
FT /note="May be involved in interaction with voltage sensor"
FT /evidence="ECO:0000269|PubMed:15051809"
FT SITE 5
FT /note="May be involved in interaction with voltage sensor"
FT /evidence="ECO:0000269|PubMed:15051809"
FT SITE 6
FT /note="May be involved in interaction with voltage sensor"
FT /evidence="ECO:0000269|PubMed:15051809"
FT SITE 22
FT /note="May be involved in interaction with voltage sensor"
FT /evidence="ECO:0000269|PubMed:15051809"
FT SITE 30
FT /note="May be involved in interaction with voltage sensor,
FT positioned at 9 angstroms from the center of the bilayer"
FT /evidence="ECO:0000269|PubMed:15051809"
FT DISULFID 2..16
FT /evidence="ECO:0000269|PubMed:14744131,
FT ECO:0000312|PDB:1LA4"
FT DISULFID 9..21
FT /evidence="ECO:0000269|PubMed:14744131,
FT ECO:0000312|PDB:1LA4"
FT DISULFID 15..28
FT /evidence="ECO:0000269|PubMed:14744131,
FT ECO:0000312|PDB:1LA4"
FT MUTAGEN 1
FT /note="T->A: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 3
FT /note="R->A: Exhibits <150-fold weaker interaction with
FT Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 4
FT /note="Y->A: Exhibits 7.5-fold weaker interaction with
FT Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 5
FT /note="L->A: Exhibits <150-fold weaker interaction with
FT Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 6
FT /note="F->A: Exhibits <300-fold weaker interaction with
FT Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 7
FT /note="G->A: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 8
FT /note="G->A: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 10
FT /note="K->A: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 11
FT /note="T->A: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 12
FT /note="T->A: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 13
FT /note="A->S: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 14
FT /note="D->A: Exhibits 6-fold tigher interaction with Kv2.1
FT channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 17
FT /note="K->A: No change in interaction with Kv2.1."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 18
FT /note="H->A: Exhibits 7.5-fold weaker interaction with
FT Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 20
FT /note="A->S: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 22
FT /note="R->A: Exhibits <150-fold weaker interaction with
FT Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 23
FT /note="S->A: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 24
FT /note="D->A: Exhibits 20-fold tigher interaction with Kv2.1
FT channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 25
FT /note="G->A: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 26
FT /note="K->A: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 29
FT /note="A->S: Exhibits 7.5-fold weaker interaction with
FT Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 30
FT /note="W->A: Exhibits <300-fold weaker interaction with
FT Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 31
FT /note="D->A: Exhibits 11.3-fold weaker interaction with
FT Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 32
FT /note="G->A: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 33
FT /note="T->A: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT MUTAGEN 34
FT /note="F->A: No change in interaction with Kv2.1 channels."
FT /evidence="ECO:0000269|PubMed:15051809"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:1LA4"
FT TURN 23..26
FT /evidence="ECO:0007829|PDB:1LA4"
SQ SEQUENCE 34 AA; 3782 MW; 31B44D44BAF814A4 CRC64;
TCRYLFGGCK TTADCCKHLA CRSDGKYCAW DGTF
