ID   3SA3_NAJMO              Reviewed;          60 AA.
AC   P01470;
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 3 {ECO:0000305};
DE   AltName: Full=CTX M4 {ECO:0000303|PubMed:8182052};
DE   AltName: Full=Cytotoxin V(II)3 {ECO:0000303|Ref.1};
OS   Naja mossambica (Mozambique spitting cobra).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX   NCBI_TaxID=8644;
RN   [1]
RP   PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   DOI=10.1016/0005-2795(74)90429-2;
RA   Louw A.I.;
RT   "Snake venom toxins. The amino acid sequences of three cytotoxin homologues
RT   from Naja mossambica mossambica venom.";
RL   Biochim. Biophys. Acta 336:481-495(1974).
RN   [2]
RP   FUNCTION, AND APPARTENANCE TO P-TYPE CYTOTOXIN GROUP.
RX   PubMed=8182052; DOI=10.1016/s0021-9258(17)36647-4;
RA   Chien K.-Y., Chiang C.-M., Hseu Y.-C., Vyas A.A., Rule G.S., Wu W.-G.;
RT   "Two distinct types of cardiotoxin as revealed by the structure and
RT   activity relationship of their interaction with zwitterionic phospholipid
RT   dispersions.";
RL   J. Biol. Chem. 269:14473-14483(1994).
CC   -!- FUNCTION: Shows cytolytic activity on many different cells by forming
CC       pore in lipid membranes (PubMed:8182052). In vivo, increases heart rate
CC       or kills the animal by cardiac arrest. In addition, it binds to heparin
CC       with high affinity, interacts with Kv channel-interacting protein 1
CC       (KCNIP1) in a calcium-independent manner, and binds to integrin alpha-
CC       V/beta-3 (ITGAV/ITGB3) with moderate affinity.
CC       {ECO:0000250|UniProtKB:P60301, ECO:0000250|UniProtKB:P60304,
CC       ECO:0000269|PubMed:8182052}.
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 1.82 mg/kg by intravenous injection.
CC   -!- MISCELLANEOUS: Is classified as a P-type cytotoxin, since a proline
CC       residue stands at position 30 (Pro-31 in standard classification).
CC       {ECO:0000305|PubMed:8182052}.
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; A01730; H3NJ3M.
DR   AlphaFoldDB; P01470; -.
DR   SMR; P01470; -.
DR   PRIDE; P01470; -.
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 3"
FT                   /evidence="ECO:0000269|Ref.1"
FT                   /id="PRO_0000093507"
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"
SQ   SEQUENCE   60 AA;  6894 MW;  01E1F6447BDD9FAE CRC64;
     LKCNRLIPPF WKTCPEGKNL CYKMTMRLAP KVPVKRGCID VCPKSSLLIK YMCCNTNKCN