3SA8_NAJKA
ID 3SA8_NAJKA Reviewed; 60 AA.
AC P60305; P01449; P01450;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 02-FEB-2004, sequence version 1.
DT 25-MAY-2022, entry version 69.
DE RecName: Full=Cytotoxin 1 {ECO:0000303|PubMed:18381281};
DE Short=CTX1;
DE Short=CX1 {ECO:0000303|PubMed:18381281};
DE AltName: Full=Cardiotoxin F8 {ECO:0000303|PubMed:1148180};
DE AltName: Full=Cardiotoxin-I {ECO:0000303|PubMed:22807058};
DE Short=CTX-I {ECO:0000303|PubMed:22807058};
DE AltName: Full=Toxin CM-6;
OS Naja kaouthia (Monocled cobra) (Naja siamensis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX NCBI_TaxID=8649;
RN [1]
RP PROTEIN SEQUENCE, SUBCELLULAR LOCATION, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=1148180; DOI=10.1021/bi00684a011;
RA Fryklund L., Eaker D.;
RT "The complete amino acid sequence of a cardiotoxin from the venom of Naja
RT naja (Cambodian Cobra).";
RL Biochemistry 14:2860-2865(1975).
RN [2]
RP PROTEIN SEQUENCE.
RC TISSUE=Venom;
RX PubMed=7210030; DOI=10.1016/0041-0101(80)90053-7;
RA Joubert F.J., Taljaard N.;
RT "The complete primary structures of three cytotoxins (CM-6, CM-7 and CM-7A)
RT from Naja naja kaouthia (Siamese cobra) snake venom.";
RL Toxicon 18:455-467(1980).
RN [3]
RP PROTEIN SEQUENCE.
RC TISSUE=Venom;
RX PubMed=3365434; DOI=10.1016/0167-4838(88)90065-9;
RA Ohkura K., Inoue S., Ikeda K., Hayashi K.;
RT "Amino-acid sequences of four cytotoxins (cytotoxins I, II, III and IV)
RT purified from the venom of the Thailand cobra, Naja naja siamensis.";
RL Biochim. Biophys. Acta 954:148-153(1988).
RN [4]
RP PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION,
RP AND SUBUNIT.
RC TISSUE=Venom;
RX PubMed=18381281; DOI=10.1074/jbc.m802085200;
RA Osipov A.V., Kasheverov I.E., Makarova Y.V., Starkov V.G., Vorontsova O.V.,
RA Ziganshin R.K., Andreeva T.V., Serebryakova M.V., Benoit A., Hogg R.C.,
RA Bertrand D., Tsetlin V.I., Utkin Y.N.;
RT "Naturally occurring disulfide-bound dimers of three-fingered toxins: a
RT paradigm for biological activity diversification.";
RL J. Biol. Chem. 283:14571-14580(2008).
RN [5]
RP FUNCTION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=22807058; DOI=10.1002/cbic.201200081;
RA Nguyen T.T., Folch B., Letourneau M., Vaudry D., Truong N.H., Doucet N.,
RA Chatenet D., Fournier A.;
RT "Cardiotoxin-I: an unexpectedly potent insulinotropic agent.";
RL ChemBioChem 13:1805-1812(2012).
RN [6]
RP FUNCTION, MUTAGENESIS OF 1-LEU--ASP-40; 40-ASP--ASN-60 AND VAL-52, AND
RP SYNTHESIS.
RX PubMed=24552570; DOI=10.1021/jm401904q;
RA Nguyen T.T., Folch B., Letourneau M., Truong N.H., Doucet N., Fournier A.,
RA Chatenet D.;
RT "Design of a truncated cardiotoxin-I analogue with potent insulinotropic
RT activity.";
RL J. Med. Chem. 57:2623-2633(2014).
CC -!- FUNCTION: Monomer: shows cytolytic activity (apoptosis is induced in
CC C2C12 cells, but no cytotoxicity is observed on INS-1E)
CC (PubMed:18381281, PubMed:22807058). In addition, this toxin shows
CC insulinotropic activity that may be mediated by the modulation of
CC potassium channels (Kv) (PubMed:22807058). It induces the increase of
CC intracellular calcium release (PubMed:24552570). It induces insulin
CC secretion from rat INS-1E cells in absence and in presence of glucose,
CC without affecting cell viability and integrity (PubMed:22807058). In
CC presence of glucose, the insulinotropic activity is increased,
CC suggesting a possible synergistic effect with glucose
CC (PubMed:22807058). Its insulinotropic activity does not involve GLP-1R
CC signaling (PubMed:22807058, PubMed:24552570).
CC {ECO:0000269|PubMed:18381281, ECO:0000269|PubMed:22807058,
CC ECO:0000269|PubMed:24552570}.
CC -!- FUNCTION: Heterodimer: has no cytolytic activity, but retains most of
CC the alpha-cobratoxin capacity to compete with alpha-bungarotoxin for
CC binding to Torpedo and alpha-7/CHRNA7 nicotinic acetylcholine receptors
CC (nAChRs) as well as to Lymnea stagnalis acetylcholine-binding protein.
CC {ECO:0000269|PubMed:18381281}.
CC -!- SUBUNIT: Monomer, or heterodimer with alpha-cobratoxin (AC P01391);
CC disulfide-linked. {ECO:0000269|PubMed:18381281}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1148180}. Target
CC cell membrane {ECO:0000250|UniProtKB:P60301}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:1148180}.
CC -!- TOXIC DOSE: LD(100) is 0.75 mg/kg by intravenous injection and 2.25
CC mg/kg by intraperitoneal injection. {ECO:0000269|PubMed:1148180}.
CC -!- MISCELLANEOUS: This toxin does not induce direct hemolysis of human
CC erythrocytes and it also does not induce potent vasoconstriction.
CC {ECO:0000269|PubMed:22807058}.
CC -!- MISCELLANEOUS: Is classified as a S-type cytotoxin, since a serine
CC residue stands at position 28 (Ser-29 in standard classification).
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain
CC subfamily. Type IA cytotoxin sub-subfamily. {ECO:0000305}.
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DR PIR; A90389; H3NJ1K.
DR AlphaFoldDB; P60305; -.
DR SMR; P60305; -.
DR TCDB; 1.C.74.1.1; the snake cytotoxin (sct) family.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR CDD; cd00206; snake_toxin; 1.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR003572; Cytotoxin_Cobra.
DR InterPro; IPR003571; Snake_3FTx.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR018354; Snake_toxin_con_site.
DR PRINTS; PR00282; CYTOTOXIN.
DR SUPFAM; SSF57302; SSF57302; 1.
DR PROSITE; PS00272; SNAKE_TOXIN; 1.
PE 1: Evidence at protein level;
KW Cardiotoxin; Cytolysis; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Membrane; Potassium channel impairing toxin;
KW Secreted; Target cell membrane; Target membrane; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT CHAIN 1..60
FT /note="Cytotoxin 1"
FT /evidence="ECO:0000269|PubMed:1148180"
FT /id="PRO_0000093498"
FT DISULFID 3..21
FT /evidence="ECO:0000250|UniProtKB:P60301"
FT DISULFID 14..38
FT /evidence="ECO:0000250|UniProtKB:P60301"
FT DISULFID 42..53
FT /evidence="ECO:0000250|UniProtKB:P60301"
FT DISULFID 54..59
FT /evidence="ECO:0000250|UniProtKB:P60301"
FT MUTAGEN 1..40
FT /note="Missing: In CTX-I(41-60); No change in cytotoxic
FT activity on INS-1E cells, decrease in intracellular calcium
FT release, no change in insulin secretion in absence of
FT glucose, decrease in insulin secretion in presence of
FT glucose. In [Lys(52)]-CTX-I(41-60); No change in cytotoxic
FT activity on INS-1E cells, no change in intracellular
FT calcium release, no change in insulin secretion in absence
FT of glucose, decrease in insulin secretion in presence of
FT glucose."
FT /evidence="ECO:0000269|PubMed:24552570"
FT MUTAGEN 40..60
FT /note="Missing: In CTX-I(1-39); gain in cytotoxic activity
FT on INS-1E cells."
FT /evidence="ECO:0000269|PubMed:24552570"
FT MUTAGEN 52
FT /note="V->K: In [Lys(52)]-CTX-I(41-60); No change in
FT cytotoxic activity on INS-1E cells, no change in
FT intracellular calcium release, no change in insulin
FT secretion in absence of glucose, decrease in insulin
FT secretion in presence of glucose."
FT /evidence="ECO:0000269|PubMed:24552570"
SQ SEQUENCE 60 AA; 6701 MW; 2FFA15E7789A7028 CRC64;
LKCNKLIPIA SKTCPAGKNL CYKMFMMSDL TIPVKRGCID VCPKNSLLVK YVCCNTDRCN
