3SA3_NAJKA
ID 3SA3_NAJKA Reviewed; 60 AA.
AC P01446;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Cytotoxin 3 {ECO:0000303|PubMed:18381281};
DE Short=CX3 {ECO:0000303|PubMed:18381281};
DE AltName: Full=Toxin CM-7 {ECO:0000303|PubMed:7210030};
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, AND SUBCELLULAR LOCATION.
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 [2]
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 [3]
RP PROTEIN SEQUENCE OF 1-30, MASS SPECTROMETRY, TOXIC DOSE, CIRCULAR DICHROISM
RP ANALYSIS, AND GLYCOSYLATION AT ASN-29.
RC TISSUE=Venom;
RX PubMed=15128311; DOI=10.1111/j.1432-1033.2004.04115.x;
RA Osipov A.V., Astapova M.V., Tsetlin V.I., Utkin Y.N.;
RT "The first representative of glycosylated three-fingered toxins. Cytotoxin
RT from the Naja kaouthia cobra venom.";
RL Eur. J. Biochem. 271:2018-2027(2004).
RN [4]
RP PROTEIN SEQUENCE OF 1-20; 23-36 AND 45-50, FUNCTION, SUBUNIT, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
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 IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=33263003; DOI=10.3389/fmolb.2020.583587;
RA Chong H.P., Tan K.Y., Tan C.H.;
RT "Cytotoxicity of Snake Venoms and Cytotoxins From Two Southeast Asian
RT Cobras (Naja sumatrana, Naja kaouthia): Exploration of Anticancer
RT Potential, Selectivity, and Cell Death Mechanism.";
RL Front. Mol. Biosci. 7:583587-583587(2020).
RN [6] {ECO:0007744|PDB:6RC7}
RP STRUCTURE BY NMR, MASS SPECTROMETRY, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DISULFIDE BONDS.
RX PubMed=33915327; DOI=10.1016/j.bbrc.2021.04.069;
RA Dubinnyi M.A., Dubovskii P.V., Starkov V.G., Utkin Y.N.;
RT "The omega-loop of cobra cytotoxins tolerates multiple amino acid
RT substitutions.";
RL Biochem. Biophys. Res. Commun. 558:141-146(2021).
CC -!- FUNCTION: Monomer: shows cytolytic activity (PubMed:18381281). Exhibits
CC concentration-dependent growth inhibitory effects in the lung cell
CC lines A549 (IC(50)=1.22 ug/ml) and NL20 (IC(50)=2.76 ug/ml), in the
CC prostate cell lines PC-3 (IC(50)=4.46 ug/ml) and RWPE-1 (IC(50)=0.65
CC ug/ml), and in the breast cell lines MCF-7 (IC(50)=12.23 ug/ml) and
CC 184B5 (IC(50)=2.83 ug/ml), with high selectivity for the lung cancer
CC cell line A549 (selectivity index=2.26) (PubMed:33263003). Induces
CC primarily necrosis in the A549 cell line, and mainly late apoptosis in
CC the MCF-7 and PC-3 cell lines (PubMed:33263003).
CC {ECO:0000269|PubMed:18381281, ECO:0000269|PubMed:33263003}.
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:33263003,
CC ECO:0000269|PubMed:33915327, ECO:0000269|PubMed:7210030}. Target cell
CC membrane {ECO:0000250|UniProtKB:P60301}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:33263003, ECO:0000305|PubMed:33915327}.
CC -!- PTM: May be regulated by glycosylation. {ECO:0000269|PubMed:15128311}.
CC -!- MASS SPECTROMETRY: Mass=6708; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:15128311, ECO:0000269|PubMed:33915327};
CC -!- TOXIC DOSE: LD(50) of the glycosylated form is 13.4 +/- 0.7 into
CC crickets (G.assimilis). {ECO:0000269|PubMed:15128311}.
CC -!- TOXIC DOSE: LD(50) of the non-glycosylated form is 5.8 +/- 0.3 nmol/g
CC into crickets (G.assimilis). {ECO:0000269|PubMed:15128311}.
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; B01712; H3NJ3K.
DR PDB; 6RC7; NMR; -; A=1-60.
DR PDBsum; 6RC7; -.
DR AlphaFoldDB; P01446; -.
DR BMRB; P01446; -.
DR SMR; P01446; -.
DR iPTMnet; P01446; -.
DR PRIDE; P01446; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:0035821; P:modulation of process of another organism; IDA:UniProtKB.
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 3D-structure; Cardiotoxin; Cytolysis; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Membrane; Secreted; Target cell membrane;
KW Target membrane; Toxin.
FT CHAIN 1..60
FT /note="Cytotoxin 3"
FT /evidence="ECO:0000269|PubMed:3365434,
FT ECO:0000269|PubMed:7210030"
FT /id="PRO_0000093500"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15128311"
FT DISULFID 3..21
FT /evidence="ECO:0000269|PubMed:33915327,
FT ECO:0007744|PDB:6RC7"
FT DISULFID 14..38
FT /evidence="ECO:0000269|PubMed:33915327,
FT ECO:0007744|PDB:6RC7"
FT DISULFID 42..53
FT /evidence="ECO:0000269|PubMed:33915327,
FT ECO:0007744|PDB:6RC7"
FT DISULFID 54..59
FT /evidence="ECO:0000269|PubMed:33915327,
FT ECO:0007744|PDB:6RC7"
FT STRAND 2..4
FT /evidence="ECO:0007829|PDB:6RC7"
FT STRAND 11..13
FT /evidence="ECO:0007829|PDB:6RC7"
FT STRAND 20..26
FT /evidence="ECO:0007829|PDB:6RC7"
FT STRAND 29..41
FT /evidence="ECO:0007829|PDB:6RC7"
FT STRAND 47..54
FT /evidence="ECO:0007829|PDB:6RC7"
SQ SEQUENCE 60 AA; 6717 MW; 84125AC5E7ED45E2 CRC64;
LKCNKLIPLA YKTCPAGKNL CYKMFMVSNK TVPVKRGCID ACPKNSLLVK YVCCNTDRCN
