3SA2_NAJAT
ID 3SA2_NAJAT Reviewed; 81 AA.
AC P01442;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 25-MAY-2022, entry version 116.
DE RecName: Full=Cytotoxin 2;
DE AltName: Full=Cardiotoxin 1A;
DE AltName: Full=Cardiotoxin 2;
DE Short=CTX-2 {ECO:0000303|PubMed:10708798};
DE AltName: Full=Cardiotoxin A2 {ECO:0000303|PubMed:16407244, ECO:0000303|PubMed:8182052};
DE Short=CTX A2 {ECO:0000303|PubMed:16407244, ECO:0000303|PubMed:8182052};
DE AltName: Full=Cardiotoxin II {ECO:0000303|PubMed:8089116, ECO:0000303|PubMed:9425035};
DE AltName: Full=Cardiotoxin analog II {ECO:0000303|PubMed:849468};
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;
RA Chu R.C., Yang C.-C.;
RL Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
RP PROTEIN SEQUENCE OF 22-81, TOXIC DOSE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=849468; DOI=10.1016/0005-2795(77)90040-x;
RA Kaneda N., Sasaki T., Hayashi K.;
RT "Primary structures of cardiotoxin analogues II and IV from the venom of
RT Naja naja atra.";
RL Biochim. Biophys. Acta 491:53-66(1977).
RN [4]
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 [5]
RP 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 [6]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=8089116; DOI=10.1016/s0021-9258(17)31544-2;
RA Bhaskaran R., Huang C.C., Tsai Y.C., Chang K.D., Yu C.;
RT "Cardiotoxin II from Taiwan cobra venom, Naja naja atra. Structure in
RT solution and comparison among homologous cardiotoxins.";
RL J. Biol. Chem. 269:23500-23508(1994).
RN [7]
RP STRUCTURE BY NMR, FUNCTION, AND DISULFIDE BONDS.
RX PubMed=9398182; DOI=10.1021/bi971107a;
RA Jang J.-Y., Kumar T.K.S., Jayaraman G., Yang P.-W., Yu C.;
RT "Comparison of the hemolytic activity and solution structures of two snake
RT venom cardiotoxin analogues which only differ in their N-terminal amino
RT acid.";
RL Biochemistry 36:14635-14641(1997).
RN [8]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=9425035; DOI=10.1021/bi971979c;
RA Lee C.-S., Kumar T.K.S., Lian L.-Y., Cheng J.-W., Yu C.;
RT "Main-chain dynamics of cardiotoxin II from Taiwan cobra (Naja naja atra)
RT as studied by carbon-13 NMR at natural abundance: delineation of the role
RT of functionally important residues.";
RL Biochemistry 37:155-164(1998).
CC -!- FUNCTION: Basic protein that binds to cell membrane and depolarizes
CC cardiomyocytes. It also shows lytic activities, but 2-fold less
CC important than that of CTX-A4. It binds to the integrin alpha-V/beta-3
CC (ITGAV/ITGB3) with a moderate affinity. It may interact with sulfatides
CC in the cell membrane which induces pore formation and cell
CC internalization and is responsible for cytotoxicity in cardiomyocytes.
CC It also may target the mitochondrial membrane and induce mitochondrial
CC swelling and fragmentation. {ECO:0000269|PubMed:9398182}.
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:0000303|PubMed:849468}. Target cell
CC membrane {ECO:0000250|UniProtKB:P60301}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC -!- TOXIC DOSE: LD(50) is 2.1 mg/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:849468}.
CC -!- TOXIC DOSE: LD(50) is 56 mg/kg by subcutaneous injection into mice.
CC {ECO:0000269|PubMed:849468}.
CC -!- MISCELLANEOUS: Is classified as a S-type cytotoxin, since a serine
CC residue stands at position 49 (Ser-29 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}.
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 EMBL; U58485; AAB18381.1; -; mRNA.
DR EMBL; U58481; AAB18377.1; -; mRNA.
DR EMBL; AJ238734; CAB42054.1; -; Genomic_DNA.
DR PIR; A01710; H3NJ2F.
DR PDB; 1CRE; NMR; -; A=22-81.
DR PDB; 1CRF; NMR; -; A=22-81.
DR PDB; 4OM4; X-ray; 2.74 A; A/B/C/D/E=22-81.
DR PDBsum; 1CRE; -.
DR PDBsum; 1CRF; -.
DR PDBsum; 4OM4; -.
DR AlphaFoldDB; P01442; -.
DR SMR; P01442; -.
DR EvolutionaryTrace; P01442; -.
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:849468"
FT CHAIN 22..81
FT /note="Cytotoxin 2"
FT /evidence="ECO:0000269|PubMed:849468"
FT /id="PRO_0000035371"
FT DISULFID 24..42
FT /evidence="ECO:0000269|PubMed:8089116,
FT ECO:0000269|PubMed:9398182, ECO:0000269|PubMed:9425035,
FT ECO:0000312|PDB:1CRE, ECO:0000312|PDB:1CRF,
FT ECO:0000312|PDB:4OM4"
FT DISULFID 35..59
FT /evidence="ECO:0000269|PubMed:8089116,
FT ECO:0000269|PubMed:9398182, ECO:0000269|PubMed:9425035,
FT ECO:0000312|PDB:1CRE, ECO:0000312|PDB:1CRF,
FT ECO:0000312|PDB:4OM4"
FT DISULFID 63..74
FT /evidence="ECO:0000269|PubMed:8089116,
FT ECO:0000269|PubMed:9398182, ECO:0000269|PubMed:9425035,
FT ECO:0000312|PDB:1CRE, ECO:0000312|PDB:1CRF,
FT ECO:0000312|PDB:4OM4"
FT DISULFID 75..80
FT /evidence="ECO:0000269|PubMed:8089116,
FT ECO:0000269|PubMed:9398182, ECO:0000269|PubMed:9425035,
FT ECO:0000312|PDB:1CRE, ECO:0000312|PDB:1CRF,
FT ECO:0000312|PDB:4OM4"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:4OM4"
FT TURN 27..30
FT /evidence="ECO:0007829|PDB:1CRE"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:4OM4"
FT STRAND 41..47
FT /evidence="ECO:0007829|PDB:4OM4"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:1CRE"
FT STRAND 55..62
FT /evidence="ECO:0007829|PDB:4OM4"
FT STRAND 68..75
FT /evidence="ECO:0007829|PDB:4OM4"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:1CRE"
SQ SEQUENCE 81 AA; 9041 MW; 182274E2FAD949BA CRC64;
MKTLLLTLVV VTIVCLDLGY TLKCNKLVPL FYKTCPAGKN LCYKMFMVSN LTVPVKRGCI
DVCPKNSALV KYVCCNTDRC N
