ID   3SA4B_NAJSP             Reviewed;          81 AA.
AC   O73856;
DT   02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 2.
DT   03-AUG-2022, entry version 80.
DE   RecName: Full=Cytotoxin 4b;
DE   AltName: Full=Cardiotoxin-4b;
DE            Short=CTX-4b;
DE            Short=Ctx4b;
DE   Flags: Precursor;
OS   Naja sputatrix (Malayan spitting cobra) (Naja naja sputatrix).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX   NCBI_TaxID=33626;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 22-71, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=9565688; DOI=10.1016/s0304-4165(97)00143-8;
RA   Jeyaseelan K., Armugam A., Lachumanan R., Tan C.H., Tan N.H.;
RT   "Six isoforms of cardiotoxin in malayan spitting cobra (Naja naja
RT   sputatrix) venom: cloning and characterization of cDNAs.";
RL   Biochim. Biophys. Acta 1380:209-222(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-81.
RC   TISSUE=Liver;
RX   PubMed=9738945; DOI=10.1016/s0014-5793(98)00894-1;
RA   Lachumanan R., Armugam A., Tan C.H., Jeyaseelan K.;
RT   "Structure and organization of the cardiotoxin genes in Naja naja
RT   sputatrix.";
RL   FEBS Lett. 433:119-124(1998).
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:9565688}. Target
CC       cell membrane {ECO:0000250|UniProtKB:P60301}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
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; U86595; AAC27690.1; -; mRNA.
DR   EMBL; AF064098; AAC61316.1; -; Genomic_DNA.
DR   AlphaFoldDB; O73856; -.
DR   SMR; O73856; -.
DR   PRIDE; O73856; -.
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:9565688"
FT   CHAIN           22..81
FT                   /note="Cytotoxin 4b"
FT                   /evidence="ECO:0000305|PubMed:9565688"
FT                   /id="PRO_0000035399"
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"
SQ   SEQUENCE   81 AA;  9084 MW;  B29A3A9142F24C8D CRC64;
     MKTLLLTLVV VTIVCLDLGY TLKCNKLVPL FYKTCPAGKN LCYKMYMVAM PKVPVKRGCI
     DVCPKSSLLV KYVCCNTDRC N