WGRTX_GRARO
ID WGRTX_GRARO Reviewed; 87 AA.
AC P60590; F8WQV8;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 2.
DT 25-MAY-2022, entry version 75.
DE RecName: Full=Omega-theraphotoxin-Gr1a {ECO:0000305};
DE Short=Omega-TRTX-Gr1a {ECO:0000305};
DE AltName: Full=Omega-grammotoxin SIA {ECO:0000303|PubMed:8394998};
DE Short=Omega-GTX SIA;
DE Short=Omega-GrTx SIA;
DE Short=Omega-GsTx SIA {ECO:0000303|PubMed:8394998};
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 50-85, AND FUNCTION.
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 50-85, AMIDATION AT VAL-85, FUNCTION, MASS
RP SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=8394998;
RA Lampe R.A., Defeo P.A., Davison M.D., Young J., Herman J.L., Spreen R.C.,
RA Horn M.B., Mangano T.J., Keith R.A.;
RT "Isolation and pharmacological characterization of omega-grammotoxin SIA, a
RT novel peptide inhibitor of neuronal voltage-sensitive calcium channel
RT responses.";
RL Mol. Pharmacol. 44:451-460(1993).
RN [3]
RP FUNCTION.
RX PubMed=8848236; DOI=10.1016/0304-3940(95)12169-2;
RA Piser T.M., Lampe R.A., Keith R.A., Thayer S.A.;
RT "Complete and reversible block by omega-grammotoxin SIA of glutamatergic
RT synaptic transmission between cultured rat hippocampal neurons.";
RL Neurosci. Lett. 201:135-138(1995).
RN [4]
RP FUNCTION.
RX PubMed=9415720; DOI=10.1124/mol.52.6.1095;
RA McDonough S.I., Lampe R.A., Keith R.A., Bean B.P.;
RT "Voltage-dependent inhibition of N- and P-type calcium channels by the
RT peptide toxin omega-grammotoxin-SIA.";
RL Mol. Pharmacol. 52:1095-1104(1997).
RN [5]
RP FUNCTION.
RX PubMed=9671721; DOI=10.1073/pnas.95.15.8585;
RA Li-Smerin Y., Swartz K.J.;
RT "Gating modifier toxins reveal a conserved structural motif in voltage-
RT gated Ca2+ and K+ channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8585-8589(1998).
RN [6]
RP FUNCTION, AND SYNTHESIS OF 50-85.
RX PubMed=29483648; DOI=10.1038/s41594-018-0033-9;
RA Correnti C.E., Gewe M.M., Mehlin C., Bandaranayake A.D., Johnsen W.A.,
RA Rupert P.B., Brusniak M.Y., Clarke M., Burke S.E., De Van Der Schueren W.,
RA Pilat K., Turnbaugh S.M., May D., Watson A., Chan M.K., Bahl C.D.,
RA Olson J.M., Strong R.K.;
RT "Screening, large-scale production and structure-based classification of
RT cystine-dense peptides.";
RL Nat. Struct. Mol. Biol. 25:270-278(2018).
RN [7]
RP STRUCTURE BY NMR OF 50-85, DISULFIDE BONDS, AND SYNTHESIS.
RX PubMed=12162963; DOI=10.1016/s0022-2836(02)00595-8;
RA Takeuchi K., Park E.J., Lee C.W., Kim J.I., Takahashi H., Swartz K.J.,
RA Shimada I.;
RT "Solution structure of omega-grammotoxin SIA, a gating modifier of P/Q and
RT N-type Ca(2+) channel.";
RL J. Mol. Biol. 321:517-526(2002).
CC -!- FUNCTION: Inhibits P/Q- (Cav2.1/CACNA1A) and N-type (Cav2.2/CACNA1B)
CC voltage-gated calcium channel by modifying voltage-dependent gating
CC (PubMed:9415720, PubMed:29483648). It selectively and reversibly blocks
CC the calcium channels coupled to glutamate release (PubMed:8848236).
CC Also inhibits potassium channels (Kv2.1/KCNB1) with lower affinity
CC (PubMed:9671721, PubMed:29483648). Has also been shown to weakly
CC inhibit Kv11.1/KCNH2/ERG1, Kv1.2/KCNA2, Kv1.3/KCNA3, Nav1.5/SCN5A,
CC Nav1.7/SCN9A and TRPV1 (PubMed:29483648). {ECO:0000269|PubMed:21740921,
CC ECO:0000269|PubMed:29483648, ECO:0000269|PubMed:8394998,
CC ECO:0000269|PubMed:8848236, ECO:0000269|PubMed:9415720,
CC ECO:0000269|PubMed:9671721}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8394998}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8394998}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:12162963}.
CC -!- MASS SPECTROMETRY: Mass=4109.2; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:8394998};
CC -!- SIMILARITY: Belongs to the neurotoxin 10 (Hwtx-1) family. 07 (GrTx)
CC subfamily. {ECO:0000305}.
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DR EMBL; AB612243; BAK55735.1; -; mRNA.
DR PDB; 1KOZ; NMR; -; A=50-85.
DR PDBsum; 1KOZ; -.
DR AlphaFoldDB; P60590; -.
DR SMR; P60590; -.
DR TCDB; 8.B.5.3.7; the na(+)/k(+)/ca(2+) channel targeting tarantula huwentoxin (tht) family.
DR ArachnoServer; AS000426; omega-theraphotoxin-Gr1a.
DR EvolutionaryTrace; P60590; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019855; F:calcium channel inhibitor activity; IDA:CACAO.
DR GO; GO:0019870; F:potassium channel inhibitor activity; IDA:CACAO.
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 Pfam; PF07740; Toxin_12; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Calcium channel impairing toxin;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Knottin; Neurotoxin; Potassium channel impairing toxin; Secreted; Signal;
KW Toxin; Voltage-gated calcium channel impairing toxin;
KW Voltage-gated potassium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..49
FT /evidence="ECO:0000269|PubMed:21740921,
FT ECO:0000269|PubMed:8394998"
FT /id="PRO_0000414297"
FT PEPTIDE 50..85
FT /note="Omega-theraphotoxin-Gr1a"
FT /evidence="ECO:0000269|PubMed:21740921,
FT ECO:0000269|PubMed:8394998"
FT /id="PRO_0000045015"
FT MOD_RES 85
FT /note="Valine amide"
FT /evidence="ECO:0000269|PubMed:8394998"
FT DISULFID 51..65
FT /evidence="ECO:0000269|PubMed:12162963,
FT ECO:0007744|PDB:1KOZ"
FT DISULFID 58..70
FT /evidence="ECO:0000269|PubMed:12162963,
FT ECO:0007744|PDB:1KOZ"
FT DISULFID 64..79
FT /evidence="ECO:0000269|PubMed:12162963,
FT ECO:0007744|PDB:1KOZ"
FT STRAND 60..64
FT /evidence="ECO:0007829|PDB:1KOZ"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:1KOZ"
FT STRAND 73..78
FT /evidence="ECO:0007829|PDB:1KOZ"
SQ SEQUENCE 87 AA; 9601 MW; 5A2B2FC706847B51 CRC64;
MKAQIFVVVL GLAALSVLCY GSEADESALH EEIFQLLAAS DEVPKPQERD CVRFWGKCSQ
TSDCCPHLAC KSKWPRNICV WDGSVGK
