ID   3SA4_NAJKA              Reviewed;          81 AA.
AC   P60303; P01444;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   02-FEB-2004, sequence version 1.
DT   25-MAY-2022, entry version 67.
DE   RecName: Full=Cytotoxin 4;
DE   AltName: Full=Cytotoxin IV;
DE   AltName: Full=Siamextin {ECO:0000303|PubMed:27558950};
DE   Flags: Precursor;
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   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RA   Li K.J., Wei J.F., Jin Y., Lu Q.M., Xiong Y.L., Wang W.Y.;
RT   "Molecular cloning and sequence analysis of cDNA of cytotoxin analog of
RT   Naja kaouthia.";
RL   Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PROTEIN SEQUENCE OF 22-81, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=2807733; DOI=10.1111/j.1399-3011.1989.tb01504.x;
RA   Chiou S.-H., Lin W.-W., Chang W.-P.;
RT   "Sequence characterization of venom toxins from Thailand cobra.";
RL   Int. J. Pept. Protein Res. 34:148-152(1989).
RN   [3]
RP   PROTEIN SEQUENCE OF 22-81.
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   PROTEIN SEQUENCE, AND NOMENCLATURE.
RX   PubMed=27558950; DOI=10.1038/srep32036;
RA   Girish V.M., Kini R.M.;
RT   "Exactin: a specific inhibitor of Factor X activation by extrinsic tenase
RT   complex from the venom of Hemachatus haemachatus.";
RL   Sci. Rep. 6:32036-32036(2016).
CC   -!- FUNCTION: Shows cytolytic activity on many different cells by forming
CC       pore in lipid membranes. In vivo, increases heart rate or kills the
CC       animal by cardiac arrest. In addition, it binds to heparin with high
CC       affinity, interacts with Kv channel-interacting protein 1 (KCNIP1) in a
CC       calcium-independent manner, and binds to integrin alpha-V/beta-3
CC       (ITGAV/ITGB3) with moderate affinity. {ECO:0000250|UniProtKB:P60301,
CC       ECO:0000250|UniProtKB:P60304}.
CC   -!- SUBUNIT: Monomer in solution; Homodimer and oligomer in the presence of
CC       negatively charged lipids forming a pore with a size ranging between 20
CC       and 30 Angstroms. {ECO:0000250|UniProtKB:P60301}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:3365434}. Target
CC       cell membrane {ECO:0000250|UniProtKB:P60301}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC   -!- TOXIC DOSE: LD(50) is 1.48 mg/kg by intraperitoneal injection.
CC   -!- MISCELLANEOUS: Is classified as a P-type cytotoxin, since a proline
CC       residue stands at position 51 (Pro-31 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   EMBL; AF295330; AAG02236.1; -; mRNA.
DR   AlphaFoldDB; P60303; -.
DR   BMRB; P60303; -.
DR   SMR; P60303; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; 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   Membrane; Secreted; Signal; Target cell membrane; Target membrane; Toxin.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000269|PubMed:2807733,
FT                   ECO:0000269|PubMed:3365434"
FT   CHAIN           22..81
FT                   /note="Cytotoxin 4"
FT                   /evidence="ECO:0000269|PubMed:2807733,
FT                   ECO:0000269|PubMed:3365434"
FT                   /id="PRO_0000035390"
FT   DISULFID        24..42
FT                   /evidence="ECO:0000250|UniProtKB:P60301"
FT   DISULFID        35..59
FT                   /evidence="ECO:0000250|UniProtKB:P60301"
FT   DISULFID        63..74
FT                   /evidence="ECO:0000250|UniProtKB:P60301"
FT   DISULFID        75..80
FT                   /evidence="ECO:0000250|UniProtKB:P60301"
FT   CONFLICT        77
FT                   /note="T -> Q (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   81 AA;  9038 MW;  70FE0A82FAC9DC95 CRC64;
     MKTLLLTLVV VTIVCLDLGY TLKCNKLVPL FYKTCPAGKN LCYKMFMVAT PKVPVKRGCI
     DVCPKSSLLV KYVCCNTDRC N