ID   3SA1_NAJME              Reviewed;          60 AA.
AC   P01448;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   03-AUG-2022, entry version 93.
DE   RecName: Full=Cytotoxin 1;
DE   AltName: Full=Cytotoxin V(II)1 {ECO:0000303|Ref.1};
OS   Naja melanoleuca (Forest cobra) (Black-lipped cobra).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX   NCBI_TaxID=8643;
RN   [1]
RP   PROTEIN SEQUENCE, TOXIC DOSE, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RA   Carlsson F.H.H., Joubert F.J.;
RT   "Snake venom toxins. The isolation and purification of three cytotoxin
RT   homologues from the venom of the forest cobra (Naja melanoleuca) and the
RT   complete amino acid sequence of toxin V(II)1.";
RL   Biochim. Biophys. Acta 336:453-469(1974).
RN   [2]
RP   SITES MET-24 AND MET-26.
RC   TISSUE=Venom;
RX   PubMed=96866; DOI=10.1016/0005-2795(78)90015-6;
RA   Carlsson F.H., Louw A.I.;
RT   "The oxidation of methionine and its effect of the properties of
RT   cardiotoxin VII1 from Naja melanoleuca venom.";
RL   Biochim. Biophys. Acta 534:322-330(1978).
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|Ref.1}. Target cell
CC       membrane {ECO:0000250|UniProtKB:P60301}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC   -!- TOXIC DOSE: LD(50) is 1.37 mg/kg by intravenous injection.
CC       {ECO:0000269|Ref.1}.
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; A01714; H3NJ1W.
DR   AlphaFoldDB; P01448; -.
DR   BMRB; P01448; -.
DR   SMR; P01448; -.
DR   PRIDE; P01448; -.
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; Target cell membrane; Target membrane; Toxin.
FT   CHAIN           1..60
FT                   /note="Cytotoxin 1"
FT                   /evidence="ECO:0000269|Ref.1"
FT                   /id="PRO_0000093502"
FT   SITE            24
FT                   /note="Important for cytolytic activity"
FT                   /evidence="ECO:0000269|PubMed:96866"
FT   SITE            26
FT                   /note="Important for cytolytic activity"
FT                   /evidence="ECO:0000269|PubMed:96866"
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   VARIANT         1
FT                   /note="L -> I (in equal amount)"
SQ   SEQUENCE   60 AA;  6682 MW;  6AD08FAB80BC44EA CRC64;
     LECNKLVPIA HKTCPAGKNL CYQMYMVSKS TIPVKRGCID VCPKSSLLVK YVCCNTDRCN