ID   3SA2_NAJMO              Reviewed;          60 AA.
AC   P01469;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   03-AUG-2022, entry version 97.
DE   RecName: Full=Cytotoxin 2;
DE   AltName: Full=CTX M2 {ECO:0000303|PubMed:8182052};
DE   AltName: Full=Cardiotoxin IIA;
DE            Short=CTX IIA;
DE   AltName: Full=Cytotoxin V(II)2;
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 S-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).
RN   [3]
RP   STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX   PubMed=2822421; DOI=10.1111/j.1432-1033.1987.tb13460.x;
RA   Otting G., Steinmetz W.E., Bougis P.E., Rochat H., Wuethrich K.;
RT   "Sequence-specific 1H-NMR assignments and determination of the secondary
RT   structure in aqueous solution of the cardiotoxins CTXIIa and CTXIIb from
RT   Naja mossambica mossambica.";
RL   Eur. J. Biochem. 168:609-620(1987).
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, 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 1.11 mg/kg by intravenous injection.
CC   -!- MISCELLANEOUS: Is classified as a S-type cytotoxin, since a serine
CC       residue stands at position 30 (Ser-29 in standard classification). S-
CC       type are generally found to exhibit higher muscle cell depolarization
CC       than P-type. {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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   PIR; A01729; H3NJ2M.
DR   AlphaFoldDB; P01469; -.
DR   BMRB; P01469; -.
DR   SMR; P01469; -.
DR   PRIDE; P01469; -.
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 2"
FT                   /evidence="ECO:0000269|Ref.1"
FT                   /id="PRO_0000093506"
FT   DISULFID        3..21
FT                   /evidence="ECO:0000269|PubMed:2822421"
FT   DISULFID        14..38
FT                   /evidence="ECO:0000269|PubMed:2822421"
FT   DISULFID        42..53
FT                   /evidence="ECO:0000269|PubMed:2822421"
FT   DISULFID        54..59
FT                   /evidence="ECO:0000269|PubMed:2822421"
SQ   SEQUENCE   60 AA;  6800 MW;  42940F1996B02A4A CRC64;
     LKCNQLIPPF WKTCPKGKNL CYKMTMRGAS KVPVKRGCID VCPKSSLLIK YMCCNTDKCN