KAX37_ORTSC
ID KAX37_ORTSC Reviewed; 38 AA.
AC P55896;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 25-MAY-2022, entry version 93.
DE RecName: Full=Potassium channel toxin alpha-KTx 3.7 {ECO:0000305};
DE AltName: Full=OsK-1 {ECO:0000303|Ref.1};
DE Short=OsK1 {ECO:0000303|PubMed:15588251, ECO:0000303|PubMed:16234482, ECO:0000303|PubMed:9063870};
OS Orthochirus scrobiculosus (Central Asian scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Orthochirus.
OX NCBI_TaxID=6892;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RA Grishin E.V., Korolkova Y.V., Kozlov S.A., Lipkin A.V., Nosyreva E.D.,
RA Pluzhnikov K.A., Sukhanov S.V., Volkova T.M.;
RT "Structure and function of the potassium channel inhibitor from black
RT scorpion venom.";
RL Pure Appl. Chem. 68:2105-2109(1996).
RN [2]
RP MUTAGENESIS OF ARG-12; GLU-16; LYS-20 AND THR-36, SYNTHESIS, TOXIC DOSE,
RP AND FUNCTION.
RX PubMed=15588251; DOI=10.1042/bj20041379;
RA Mouhat S., Visan V., Ananthakrishnan S., Wulff H., Andreotti N.,
RA Grissmer S., Darbon H., De Waard M., Sabatier J.-M.;
RT "K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus
RT scrobiculosus scorpion venom.";
RL Biochem. J. 385:95-104(2005).
RN [3]
RP MUTAGENESIS, AND FUNCTION.
RX PubMed=16234482; DOI=10.1124/mol.105.017210;
RA Mouhat S., Teodorescu G., Homerick D., Visan V., Wulff H., Wu Y.,
RA Grissmer S., Darbon H., De Waard M., Sabatier J.-M.;
RT "Pharmacological profiling of Orthochirus scrobiculosus toxin 1 analogs
RT with a trimmed N-terminal domain.";
RL Mol. Pharmacol. 69:354-362(2006).
RN [4]
RP FUNCTION, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=31276191; DOI=10.1002/1873-3468.13530;
RA Kasheverov I.E., Oparin P.B., Zhmak M.N., Egorova N.S., Ivanov I.A.,
RA Gigolaev A.M., Nekrasova O.V., Serebryakova M.V., Kudryavtsev D.S.,
RA Prokopev N.A., Hoang A.N., Tsetlin V.I., Vassilevski A.A., Utkin Y.N.;
RT "Scorpion toxins interact with nicotinic acetylcholine receptors.";
RL FEBS Lett. 593:2779-2789(2019).
RN [5]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=9063870; DOI=10.1021/bi9614390;
RA Jaravine V.A., Nolde D.E., Reibarkh M.J., Korolkova Y.V., Kozlov S.A.,
RA Pluzhnikov K.A., Grishin E.V., Arseniev A.S.;
RT "Three-dimensional structure of toxin OSK1 from Orthochirus scrobiculosus
RT scorpion venom.";
RL Biochemistry 36:1223-1232(1997).
CC -!- FUNCTION: Blocks voltage-gated potassium channels Kv1.1/KCNA1
CC (IC(50)=0.6 nM), Kv1.2/KCNA2 (IC(50)=5.4 nM), Kv1.3/KCNA3 (IC(50)=0.014
CC nM) potently, and moderately block intermediate conductance calcium-
CC activated potassium channels KCa3.1/KCNN4 (IC(50)=225 nM)
CC (PubMed:15588251, Ref.1, PubMed:16234482). Also shows activity on
CC muscle-type nicotinic acetylcholine receptor (nAChR), since it
CC reversibly and dose-dependently inhibits acetylcholine-induced current
CC through mouse muscle-type nAChR heterologously expressed in Xenopus
CC oocytes (IC(50)=1.6 uM) (PubMed:31276191).
CC {ECO:0000269|PubMed:15588251, ECO:0000269|PubMed:16234482,
CC ECO:0000269|PubMed:31276191, ECO:0000269|Ref.1}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.1}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|Ref.1}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to a
CC beta-sheet by disulfide bonds (CSalpha/beta).
CC {ECO:0000269|PubMed:9063870}.
CC -!- MASS SPECTROMETRY: Mass=4205.3; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:31276191};
CC -!- TOXIC DOSE: LD(50) is 2 ug/kg by intracerebroventricular injection into
CC mice. {ECO:0000269|PubMed:15588251}.
CC -!- MISCELLANEOUS: Does not show activity on Kv1.4/KCNA4, Kv1.5/KCNA5,
CC Kv1.6/KCNA6, Kv1.7/KCNA7, Kv3.1/KCNC1, Kv11.x/KCNH, KCa1.1/KCNMA1,
CC KCa2.1/KCNN1, KCa2.2/KCNN2, and KCa2.3/KCNN3 (PubMed:15588251). Does
CC not show activity on Kv3.2/KCNC2 (PubMed:16234482). May not inhibit
CC neuronal human alpha-7 nAChR, since it does not inhibit alpha-7 alpha-
CC bungarotoxin binding (IC(50)~20 uM) (PubMed:31276191).
CC {ECO:0000269|PubMed:15588251, ECO:0000269|PubMed:16234482,
CC ECO:0000269|PubMed:31276191, ECO:0000269|Ref.1}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 03 subfamily. {ECO:0000305}.
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DR PDB; 1SCO; NMR; -; A=1-38.
DR PDB; 2CK4; NMR; -; A=1-38.
DR PDB; 2CK5; NMR; -; A=8-38.
DR PDBsum; 1SCO; -.
DR PDBsum; 2CK4; -.
DR PDBsum; 2CK5; -.
DR AlphaFoldDB; P55896; -.
DR SMR; P55896; -.
DR EvolutionaryTrace; P55896; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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 Gene3D; 3.30.30.10; -; 1.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR InterPro; IPR001947; Scorpion_toxinS_K_inh.
DR Pfam; PF00451; Toxin_2; 1.
DR PRINTS; PR00286; CHARYBDTOXIN.
DR SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS01138; SCORP_SHORT_TOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium-activated potassium channel impairing toxin;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Potassium channel impairing toxin; Secreted; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT PEPTIDE 1..38
FT /note="Potassium channel toxin alpha-KTx 3.7"
FT /evidence="ECO:0000269|Ref.1"
FT /id="PRO_0000044909"
FT DISULFID 8..28
FT /evidence="ECO:0000269|PubMed:9063870,
FT ECO:0000312|PDB:1SCO, ECO:0000312|PDB:2CK4,
FT ECO:0000312|PDB:2CK5"
FT DISULFID 14..33
FT /evidence="ECO:0000269|PubMed:9063870,
FT ECO:0000312|PDB:1SCO, ECO:0000312|PDB:2CK4,
FT ECO:0000312|PDB:2CK5"
FT DISULFID 18..35
FT /evidence="ECO:0000269|PubMed:9063870,
FT ECO:0000312|PDB:1SCO, ECO:0000312|PDB:2CK4,
FT ECO:0000312|PDB:2CK5"
FT MUTAGEN 12
FT /note="R->P: Loss of activity; when associated with K-16
FT and D-20."
FT /evidence="ECO:0000269|PubMed:15588251"
FT MUTAGEN 16
FT /note="E->K: No change in activity. 1 to 2-fold increase in
FT activity on Kv1.1/KCNA1, Kv1.2/KCNA2 and Kv1.3/KCNA3
FT without affecting activity on KCa3.1/KCNMA1; when
FT associated with K-20. Loss of activity; when associated
FT with R-12 and D-20. Loss of activity; when associated with
FT D-20 and T-36."
FT /evidence="ECO:0000269|PubMed:15588251"
FT MUTAGEN 20
FT /note="K->D: 3-fold reduction of activity. 1 to 2-fold
FT increase in activity on Kv1.1/KCNA1, Kv1.2/KCNA2 and
FT Kv1.3/KCNA3 without affecting activity on KCa3.1/KCNMA1;
FT when associated with E-16. Loss of activity; when
FT associated with R-12 and K-16. Loss of activity; when
FT associated with K-16 and T-36."
FT /evidence="ECO:0000269|PubMed:15588251"
FT MUTAGEN 36
FT /note="T->Y: Loss of activity; when associated with K-16
FT and D-20."
FT /evidence="ECO:0000269|PubMed:15588251"
FT STRAND 2..4
FT /evidence="ECO:0007829|PDB:1SCO"
FT HELIX 11..21
FT /evidence="ECO:0007829|PDB:1SCO"
FT STRAND 23..29
FT /evidence="ECO:0007829|PDB:1SCO"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:1SCO"
SQ SEQUENCE 38 AA; 4211 MW; 4E900CFE46E17421 CRC64;
GVIINVKCKI SRQCLEPCKK AGMRFGKCMN GKCHCTPK
