AF1_GRARO
ID AF1_GRARO Reviewed; 29 AA.
AC P61408;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 1.
DT 25-MAY-2022, entry version 52.
DE RecName: Full=Beta-theraphotoxin-Gr1b {ECO:0000303|PubMed:31234412};
DE Short=Beta-TRTX-Gr1b {ECO:0000303|PubMed:31234412};
DE AltName: Full=GsAF 1;
DE Short=GsAf1 {ECO:0000303|PubMed:30661758};
DE AltName: Full=GsAF I {ECO:0000303|Ref.1};
DE Short=GsAFI {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, MASS SPECTROMETRY, AND
RP AMIDATION AT LEU-29.
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 [2]
RP PROTEIN SEQUENCE, MASS SPECTROMETRY, FUNCTION, AND SUBCELLULAR LOCATION.
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.
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 the voltage-gated sodium channels Nav1.1/SCN1A
CC (IC(50)=360 nM), Nav1.2/SCN2A (IC(50)=600 nM), Nav1.3/SCN3A
CC (IC(50)=1280), Nav1.4/SCN4A (IC(50)=330 nM), Nav1.6/SCN8A (IC(50)=1200
CC nM), Nav1.7/SCN9A (IC(50)=1-40 nM), and voltage-gated potassium
CC channels Kv11.1/KCNH2 (IC(50)=4.8 uM) (PubMed:19955179,
CC PubMed:30661758, PubMed:31234412). Induces analgesia in mammals
CC (Ref.1). This analgesia is mediated by a non-opioid receptor related
CC mechanism (Ref.1). {ECO:0000269|PubMed:19955179,
CC ECO:0000269|PubMed:30661758, ECO:0000269|PubMed:31234412,
CC ECO:0000269|Ref.1}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19955179,
CC ECO:0000269|Ref.1}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|Ref.1}.
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=3713.5; Method=Electrospray;
CC Evidence={ECO:0000269|Ref.1};
CC -!- MASS SPECTROMETRY: Mass=3707.0; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:19955179};
CC -!- MISCELLANEOUS: This toxin does not inhibit sodium channels
CC Nav1.5/SCN5A, and potassium channels Kv1.1/KCNA1, Kv1.4/KCNA4,
CC Kv11.2/KCNH6, Kv11.3/KCNH7 (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; P61408; -.
DR SMR; P61408; -.
DR ArachnoServer; AS000026; beta-theraphotoxin-Gr1b.
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 Amidation; 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;
KW Voltage-gated sodium channel impairing toxin.
FT PEPTIDE 1..29
FT /note="Beta-theraphotoxin-Gr1b"
FT /evidence="ECO:0000269|PubMed:19955179, ECO:0000269|Ref.1"
FT /id="PRO_0000044551"
FT MOD_RES 29
FT /note="Leucine amide"
FT /evidence="ECO:0000269|Ref.1"
FT DISULFID 2..16
FT /evidence="ECO:0000250|UniProtKB:P61230"
FT DISULFID 9..21
FT /evidence="ECO:0000250|UniProtKB:P61230"
FT DISULFID 15..25
FT /evidence="ECO:0000250|UniProtKB:P61230"
SQ SEQUENCE 29 AA; 3714 MW; 9CF2F630431B9B37 CRC64;
YCQKWLWTCD SERKCCEDMV CRLWCKKRL
