3SAN_NAJAT
ID 3SAN_NAJAT Reviewed; 81 AA.
AC P80245; P49124; Q9PWQ7;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2002, sequence version 2.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Cytotoxin 6;
DE AltName: Full=Cardiotoxin 6;
DE Short=CTX6;
DE AltName: Full=Cardiotoxin A6 {ECO:0000303|PubMed:16407244};
DE Short=CTX A6 {ECO:0000303|PubMed:16407244};
DE AltName: Full=Cardiotoxin N {ECO:0000303|PubMed:8619792};
DE Short=CTXN;
DE Short=Ctx-N;
DE AltName: Full=Cytotoxin N;
DE Flags: Precursor;
OS Naja atra (Chinese cobra).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX NCBI_TaxID=8656;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=8619792; DOI=10.1006/bbrc.1996.0191;
RA Chang L.-S., Wu P.-F., Lin J.;
RT "cDNA sequence analysis and expression of cardiotoxins from Taiwan Cobra.";
RL Biochem. Biophys. Res. Commun. 219:116-121(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RA Chu R.C., Yang C.-C.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RA Qian Y.C., Fan C.Y., Gong Y., Yang S.;
RT "cDNA cloning and expression of cardiotoxins from Chinese continental
RT cobra.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=10708798; DOI=10.1016/s0041-0101(99)00218-4;
RA Chang L.-S., Huang H.-B., Lin S.-R.;
RT "The multiplicity of cardiotoxins from Naja naja atra (Taiwan cobra)
RT venom.";
RL Toxicon 38:1065-1076(2000).
RN [5]
RP PROTEIN SEQUENCE OF 22-81, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=8193587;
RA Hung C.C., Wu S.-H., Chiou S.-H.;
RT "Sequence characterization of cardiotoxins from Taiwan cobra: isolation of
RT a new isoform.";
RL Biochem. Mol. Biol. Int. 31:1031-1040(1993).
RN [6]
RP FUNCTION, AND BINDING TO INTEGRIN ALPHA-V/BETA-3.
RX PubMed=16407244; DOI=10.1074/jbc.m513035200;
RA Wu P.-L., Lee S.-C., Chuang C.-C., Mori S., Akakura N., Wu W.-G.,
RA Takada Y.;
RT "Non-cytotoxic cobra cardiotoxin A5 binds to alpha(v)beta3 integrin and
RT inhibits bone resorption. Identification of cardiotoxins as non-RGD
RT integrin-binding proteins of the Ly-6 family.";
RL J. Biol. Chem. 281:7937-7945(2006).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 22-81, AND DISULFIDE BOND.
RX PubMed=15895985; DOI=10.1021/bi050172e;
RA Chen T.-S., Chung F.-Y., Tjong S.-C., Goh K.-S., Huang W.-N., Chien K.-Y.,
RA Wu P.-L., Lin H.-C., Chen C.-J., Wu W.-G.;
RT "Structural difference between group I and group II cobra cardiotoxins: X-
RT ray, NMR, and CD analysis of the effect of cis-proline conformation on
RT three-fingered toxins.";
RL Biochemistry 44:7414-7426(2005).
CC -!- FUNCTION: Basic protein that bind to cell membrane and depolarizes
CC cardiomyocytes. This cytotoxin also shows lytic activities, on many
CC other cells including red blood cells. Interaction with sulfatides in
CC the cell membrane induces pore formation and cell internalization and
CC is responsible for cytotoxicity in cardiomyocytes. It targets the
CC mitochondrial membrane and induces mitochondrial swelling and
CC fragmentation. Inhibits protein kinases C (By similarity). It binds to
CC the integrin alpha-V/beta-3 with a moderate affinity (PubMed:16407244).
CC {ECO:0000250|UniProtKB:P01443, ECO:0000269|PubMed:16407244}.
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:8193587}. Target
CC cell membrane {ECO:0000250|UniProtKB:P60301}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC -!- MISCELLANEOUS: Shows a cis peptide bond at 29-Pro-Pro-30.
CC {ECO:0000269|PubMed:15895985}.
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; Z54230; CAA90966.1; -; mRNA.
DR EMBL; AF031474; AAB86638.1; -; mRNA.
DR EMBL; AJ007797; CAA07687.1; -; mRNA.
DR EMBL; AJ238738; CAB42058.1; -; Genomic_DNA.
DR PIR; JC4621; JC4621.
DR PDB; 1UG4; X-ray; 1.60 A; A=22-81.
DR PDBsum; 1UG4; -.
DR AlphaFoldDB; P80245; -.
DR SMR; P80245; -.
DR PRIDE; P80245; -.
DR EvolutionaryTrace; P80245; -.
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:0044179; P:hemolysis in another organism; 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 3D-structure; Cardiotoxin; Cytolysis; Direct protein sequencing;
KW Disulfide bond; Hemolysis; Membrane; Secreted; Signal;
KW Target cell membrane; Target membrane; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:8193587"
FT CHAIN 22..81
FT /note="Cytotoxin 6"
FT /evidence="ECO:0000269|PubMed:8193587"
FT /id="PRO_0000035380"
FT DISULFID 24..42
FT /evidence="ECO:0000269|PubMed:15895985,
FT ECO:0000312|PDB:1UG4"
FT DISULFID 35..59
FT /evidence="ECO:0000269|PubMed:15895985,
FT ECO:0000312|PDB:1UG4"
FT DISULFID 63..74
FT /evidence="ECO:0000269|PubMed:15895985,
FT ECO:0000312|PDB:1UG4"
FT DISULFID 75..80
FT /evidence="ECO:0000269|PubMed:15895985,
FT ECO:0000312|PDB:1UG4"
FT CONFLICT 11
FT /note="V -> A (in Ref. 1; CAA90966)"
FT /evidence="ECO:0000305"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:1UG4"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:1UG4"
FT STRAND 41..47
FT /evidence="ECO:0007829|PDB:1UG4"
FT STRAND 55..62
FT /evidence="ECO:0007829|PDB:1UG4"
FT STRAND 68..75
FT /evidence="ECO:0007829|PDB:1UG4"
SQ SEQUENCE 81 AA; 8980 MW; 284A608DBACA87A9 CRC64;
MKTLLLTLVV VTIVCLDLGY TLKCNQLIPP FYKTCAAGKN LCYKMFMVAA PKVPVKRGCI
DVCPKSSLLV KYVCCNTDRC N
