ID   AF2_GRARO               Reviewed;          81 AA.
AC   P61409; F8WQV7;
DT   24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT   14-DEC-2011, sequence version 2.
DT   25-JAN-2012, entry version 29.
DE   RecName: Full=Kappa-theraphotoxin-Gr2c;
DE            Short=Kappa-TRTX-Gr2c;
DE   AltName: Full=GsAF II;
DE            Short=GsAFII;
DE   AltName: Full=Mechanotoxin-alpha;
DE   Flags: Precursor;
OS   Grammostola rosea (Chilean rose tarantula) (Grammostola spatulata).
OC   Eukaryota; Metazoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Mygalomorphae; Theraphosidae; Grammostola.
OX   NCBI_TaxID=432528;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 51-81, 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
RT   peptides 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, TISSUE
RP   SPECIFICITY, AND MASS SPECTROMETRY.
RC   TISSUE=Venom;
RA   Lampe R.A.;
RT   "Analgesic peptides from venom of Grammostola spatulata and use
RT   thereof.";
RL   Patent number US5877026, 02-MAR-1999.
RN   [3]
RP   PROTEIN SEQUENCE OF 51-81, FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND MASS 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, FUNCTION, AND TOXIN
RP   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
RT   peptides affecting Na+ and K+ ion channels.";
RL   J. Biol. Chem. 285:4130-4142(2010).
CC   -!- FUNCTION: Inhibits sodium channels Nav1.1/SCN1A, Nav1.2/SCN2A,
CC       Nav1.4/SCN4A, Nav1.6/SCN8A, Nav1.7/SCN9A, potassium channels
CC       Kv11.1/KCNH2, as well as high-voltage-gated calcium channels
CC       Cav1.2/CACNA1C. Also blocks mechanosensitive ion channels (also
CC       named strech-activated channels or SACs) and the hypotonic cell
CC       swelling induced calcium increase associated with the activation
CC       of such channels. It can thus be useful in treating cardiac
CC       ventricular disturbances. Also induces analgesia in mammals. This
CC       analgesia is probably mediated by a non-opioid receptor related
CC       mechanism.
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 (By similarity).
CC   -!- MASS SPECTROMETRY: Mass=3979.9; Method=Electrospray; Range=51-81;
CC       Source=Ref.2, Ref.3;
CC   -!- MASS SPECTROMETRY: Mass=3980.0; Method=Unknown; Range=51-81;
CC       Source=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) (PubMed:19955179).
CC   -!- SIMILARITY: Belongs to the phrixotoxin family.
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DR   EMBL; AB612242; BAK55734.1; -; mRNA.
DR   ProteinModelPortal; P61409; -.
DR   ArachnoServer; AS000027; kappa-theraphotoxin-Gr2c.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0019870; F:potassium channel inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0019871; F:sodium channel inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0009405; P:pathogenesis; IEA:InterPro.
PE   1: Evidence at protein level;
KW   Calcium channel inhibitor; Direct protein sequencing; Disulfide bond;
KW   Ionic channel inhibitor; Knottin; Potassium channel inhibitor;
KW   Secreted; Signal; Sodium channel inhibitor; Toxin.
FT   SIGNAL        1     19       Potential.
FT   PROPEP       20     50
FT                                /FTId=PRO_0000414298.
FT   PEPTIDE      51     81       Kappa-theraphotoxin-Gr2c.
FT                                /FTId=PRO_0000045016.
FT   DISULFID     52     66       By similarity.
FT   DISULFID     59     71       By similarity.
FT   DISULFID     65     75       By similarity.
FT   CONFLICT     81     81       Missing (in Ref. 1; AA sequence).
SQ   SEQUENCE   81 AA;  9679 MW;  8BD59C517DAA704C CRC64;
     MKAFFVILGL ALLCAYSFAL EEQDQLSLRN DLLTVMFAEN SELTPETEER YCQKWMWTCD
     EERKCCEGLV CRLWCKKKIE W
//