KA101_CENNO
ID KA101_CENNO Reviewed; 62 AA.
AC O46028;
DT 19-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 25-MAY-2022, entry version 97.
DE RecName: Full=Potassium channel toxin alpha-KTx 10.1;
DE AltName: Full=Cobatoxin-1 {ECO:0000303|PubMed:9688256};
DE Short=CoTx1 {ECO:0000303|PubMed:9688256};
DE AltName: Full=gtIX;
DE Flags: Precursor;
OS Centruroides noxius (Mexican scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Centruroides.
OX NCBI_TaxID=6878;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 29-60, FUNCTION,
RP SUBCELLULAR LOCATION, AND AMIDATION AT TYR-60.
RC TISSUE=Venom, and Venom gland;
RX PubMed=9688256; DOI=10.1046/j.1432-1327.1998.2540468.x;
RA Selisko B., Garcia C., Becerril B., Gomez-Lagunas F., Garay C.,
RA Possani L.D.;
RT "Cobatoxins 1 and 2 from Centruroides noxius Hoffmann constitute a new
RT subfamily of potassium-channel-blocking scorpion toxins.";
RL Eur. J. Biochem. 254:468-479(1998).
RN [2]
RP STRUCTURE BY NMR OF 29-60, FUNCTION, DISULFIDE BONDS, SUBCELLULAR LOCATION,
RP TOXIC DOSE, SYNTHESIS OF 29-60, MUTAGENESIS OF 35-THR--ASP-37, AND
RP CHANNEL-TOXIN INTERACTION MODELING.
RC TISSUE=Venom;
RX PubMed=14498829; DOI=10.1042/bj20030977;
RA Jouirou B., Mosbah A., Visan V., Grissmer S., M'Barek S., Fajloun Z.,
RA Van Rietschoten J., Devaux C., Rochat H., Lippens G., El Ayeb M.,
RA De Waard M., Mabrouk K., Sabatier J.-M.;
RT "Cobatoxin 1 from Centruroides noxius scorpion venom: chemical synthesis,
RT three-dimensional structure in solution, pharmacology and docking on K+
RT channels.";
RL Biochem. J. 377:37-49(2004).
CC -!- FUNCTION: Blocks Shaker B (Sh) and voltage-gated potassium-channels
CC Kv1.1/KCNA1, Kv1.2/KCNA2, Kv1.3/KCNA3. Also inhibits small conductance
CC calcium-activated potassium channels (KCNN) and intermediate
CC conductance calcium-activated potassium channel (KCa3.1/KCNN4).
CC {ECO:0000269|PubMed:14498829, ECO:0000269|PubMed:9688256}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14498829,
CC ECO:0000269|PubMed:9688256}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:14498829, ECO:0000305|PubMed:9688256}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to a
CC beta-sheet by disulfide bonds (CSalpha/beta).
CC -!- TOXIC DOSE: LD(50) is 25 ug/kg by intracerebroventricular injection
CC into mice. {ECO:0000269|PubMed:14498829}.
CC -!- MISCELLANEOUS: This toxin does not inhibit Kv1.5/KCNA5 and Kv3.1/KCNC1.
CC {ECO:0000305|PubMed:14498829}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 10 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ224689; CAA12073.1; -; mRNA.
DR PDB; 1PJV; NMR; -; A=29-60.
DR PDBsum; 1PJV; -.
DR AlphaFoldDB; O46028; -.
DR SMR; O46028; -.
DR EvolutionaryTrace; O46028; -.
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:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.30.10; -; 1.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS01138; SCORP_SHORT_TOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation;
KW Calcium-activated potassium channel impairing toxin;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Potassium channel impairing toxin; Secreted; Signal; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..28
FT /evidence="ECO:0000305|PubMed:9688256"
FT /id="PRO_0000232655"
FT CHAIN 29..60
FT /note="Potassium channel toxin alpha-KTx 10.1"
FT /evidence="ECO:0000269|PubMed:9688256"
FT /id="PRO_0000035327"
FT SITE 34
FT /note="Important for the interaction with Kv1.2/KCNA2
FT channel"
FT /evidence="ECO:0000305|PubMed:14498829"
FT SITE 38
FT /note="Important for the interaction with Kv1.2/KCNA2
FT channel"
FT /evidence="ECO:0000305|PubMed:14498829"
FT SITE 42
FT /note="Important for the interaction with Kv1.2/KCNA2
FT channel"
FT /evidence="ECO:0000305|PubMed:14498829"
FT SITE 46
FT /note="Important for the interaction with Kv1.2/KCNA2
FT channel"
FT /evidence="ECO:0000305|PubMed:14498829"
FT SITE 49
FT /note="Basic residue of the functional dyad, important for
FT the interaction with Kv1.2/KCNA2 channel"
FT /evidence="ECO:0000305|PubMed:14498829"
FT SITE 51
FT /note="Important for the interaction with Kv1.2/KCNA2
FT channel"
FT /evidence="ECO:0000305|PubMed:14498829"
FT SITE 52
FT /note="Important for the interaction with Kv1.2/KCNA2
FT channel"
FT /evidence="ECO:0000305|PubMed:14498829"
FT SITE 56
FT /note="Important for the interaction with Kv1.2/KCNA2
FT channel"
FT /evidence="ECO:0000305|PubMed:14498829"
FT SITE 58
FT /note="Aromatic residue of the functional dyad, important
FT for the interaction with Kv1.2/KCNA2 channel"
FT /evidence="ECO:0000305|PubMed:14498829"
FT MOD_RES 60
FT /note="Tyrosine amide"
FT /evidence="ECO:0000269|PubMed:9688256"
FT DISULFID 31..50
FT /evidence="ECO:0000269|PubMed:14498829,
FT ECO:0007744|PDB:1PJV"
FT DISULFID 36..55
FT /evidence="ECO:0000269|PubMed:14498829,
FT ECO:0007744|PDB:1PJV"
FT DISULFID 40..57
FT /evidence="ECO:0000269|PubMed:14498829,
FT ECO:0007744|PDB:1PJV"
FT MUTAGEN 35..37
FT /note="TCD->PCQ: Increases the toxicity (LD(50)=15 ug/kg).
FT Inhibits KCNN with the same intensity. Inhibits more
FT efficiently KCNN4, Sh KCNA1, KCNA2, and KCNA3."
FT /evidence="ECO:0000269|PubMed:14498829"
FT HELIX 33..41
FT /evidence="ECO:0007829|PDB:1PJV"
FT TURN 42..44
FT /evidence="ECO:0007829|PDB:1PJV"
FT STRAND 45..51
FT /evidence="ECO:0007829|PDB:1PJV"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:1PJV"
SQ SEQUENCE 62 AA; 7131 MW; 32CEAE093B6971A0 CRC64;
MEGIAKITLI LLFLFVTMHT FANWNTEAAV CVYRTCDKDC KRRGYRSGKC INNACKCYPY
GK
