ID   3SA9_NAJNA              Reviewed;          72 AA.
AC   A0A0U5AUY6; C0HJU1;
DT   06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT   16-MAR-2016, sequence version 1.
DT   03-AUG-2022, entry version 21.
DE   RecName: Full=Cytotoxin 9 {ECO:0000312|EMBL:BAU24665.1};
DE            Short=CTX9 {ECO:0000312|EMBL:BAU24665.1};
DE   Flags: Precursor; Fragment;
OS   Naja naja (Indian cobra).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX   NCBI_TaxID=35670 {ECO:0000312|EMBL:BAU24665.1};
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 13-72, FUNCTION, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Venom {ECO:0000303|PubMed:26456928}, and
RC   Venom gland {ECO:0000312|EMBL:BAU24665.1};
RX   PubMed=26456928; DOI=10.1016/j.cbpc.2015.09.015;
RA   Suzuki-Matsubara M., Athauda S.B.P., Suzuki Y., Matsubara R.A.K.,
RA   Moriyama A.;
RT   "Comparison of the primary structures, cytotoxicities, and affinities to
RT   phospholipids of five kinds of cytotoxins from the venom of Indian cobra,
RT   Naja naja.";
RL   Comp. Biochem. Physiol. 179C:158-164(2016).
RN   [2] {ECO:0000305}
RP   PROTEIN SEQUENCE OF 13-42, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom {ECO:0000303|PubMed:20203422};
RX   PubMed=20203422; DOI=10.2220/biomedres.31.71;
RA   Suzuki M., Itoh T., Bandaranayake B.M.A.I.K., Ranasinghe J.G.,
RA   Athauda S.B., Moriyama A.;
RT   "Molecular diversity in venom proteins of the Russell's viper (Daboia
RT   russellii russellii) and the Indian cobra (Naja naja) in Sri Lanka.";
RL   Biomed. Res. 31:71-81(2010).
CC   -!- FUNCTION: Shows cytolytic activity on many different cells by forming a
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 (By similarity). Preferentially
CC       binds acidic phospholipids like phosphatidylserine, phosphatidic acid
CC       and phosphatidyl glycerol (PubMed:26456928). Has hemolytic activity
CC       towards human erythrocytes (EC(50)=0.171 uM) and cytolytic activity
CC       towards various cell lines (PubMed:26456928).
CC       {ECO:0000250|UniProtKB:P60301, ECO:0000250|UniProtKB:P60304,
CC       ECO:0000269|PubMed:26456928}.
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:0000255,
CC       ECO:0000255|RuleBase:RU003614, ECO:0000269|PubMed:20203422,
CC       ECO:0000269|PubMed:26456928}.
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 42 (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; LC015651; BAU24665.1; -; mRNA.
DR   AlphaFoldDB; A0A0U5AUY6; -.
DR   SMR; A0A0U5AUY6; -.
DR   Proteomes; UP000694559; Unplaced.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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   Reference proteome; Secreted; Signal; Toxin.
FT   SIGNAL          <1..12
FT                   /evidence="ECO:0000305|PubMed:20203422,
FT                   ECO:0000305|PubMed:26456928"
FT   CHAIN           13..72
FT                   /note="Cytotoxin 9"
FT                   /evidence="ECO:0000269|PubMed:26456928"
FT                   /id="PRO_0000436849"
FT   DISULFID        15..33
FT                   /evidence="ECO:0000250|UniProtKB:P01440"
FT   DISULFID        26..50
FT                   /evidence="ECO:0000250|UniProtKB:P01440"
FT   DISULFID        54..65
FT                   /evidence="ECO:0000250|UniProtKB:P01440"
FT   DISULFID        66..71
FT                   /evidence="ECO:0000250|UniProtKB:P01440"
FT   NON_TER         1
FT                   /evidence="ECO:0000312|EMBL:BAU24665.1"
SQ   SEQUENCE   72 AA;  8041 MW;  DA0A0D6DDD8F048D CRC64;
     VVTIVCLDLG YTLKCNKLVP LFYKTCPAGK NLCYKMYMVA TPKVPVKRGC IDVCPKSSLL
     VKYVCCNTDR CN