3SA1_NAJAT
ID 3SA1_NAJAT Reviewed; 81 AA.
AC P60304; P01449; P01450; Q9PS24; Q9W6W8;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 02-FEB-2004, sequence version 1.
DT 25-MAY-2022, entry version 84.
DE RecName: Full=Cytotoxin 1;
DE Short=CX1;
DE AltName: Full=Cardiotoxin 1;
DE Short=CTX-1;
DE Short=CTX1;
DE AltName: Full=Cardiotoxin A1 {ECO:0000303|PubMed:16407244, ECO:0000303|PubMed:8182052};
DE Short=CTX A1 {ECO:0000303|PubMed:16407244, ECO:0000303|PubMed:8182052};
DE AltName: Full=Cardiotoxin I {ECO:0000303|PubMed:8619792};
DE AltName: Full=Cardiotoxin analog I;
DE Short=CTX I;
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 (DEC-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP PROTEIN SEQUENCE OF 22-81, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=1147930; DOI=10.1016/0006-291x(75)90262-4;
RA Hayashi K., Takechi M., Sasaki T., Lee C.Y.;
RT "Amino acid sequence of cardiotoxin-analogue I from the venom of Naja naja
RT atra.";
RL Biochem. Biophys. Res. Commun. 64:360-366(1975).
RN [5]
RP PROTEIN SEQUENCE OF 22-81, AND FUNCTION AS AN INHIBITOR OF PKC.
RX PubMed=8448165; DOI=10.1021/bi00059a025;
RA Chiou S.-H., Raynor R.L., Zheng B., Chambers T.C., Kuo J.F.;
RT "Cobra venom cardiotoxin (cytotoxin) isoforms and neurotoxin: comparative
RT potency of protein kinase C inhibition and cancer cell cytotoxicity and
RT modes of enzyme inhibition.";
RL Biochemistry 32:2062-2067(1993).
RN [6]
RP FUNCTION AS MYOTOXIN.
RC TISSUE=Venom;
RX PubMed=8342169; DOI=10.1016/0041-0101(93)90376-t;
RA Ownby C.L., Fletcher J.E., Colberg T.R.;
RT "Cardiotoxin 1 from cobra (Naja naja atra) venom causes necrosis of
RT skeletal muscle in vivo.";
RL Toxicon 31:697-709(1993).
RN [7]
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 [8]
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 [9]
RP FUNCTION, AND BINDING TO HEPARIN.
RX PubMed=17685633; DOI=10.1021/bi700995v;
RA Tjong S.C., Chen T.S., Huang W.N., Wu W.G.;
RT "Structures of heparin-derived tetrasaccharide bound to cobra cardiotoxins:
RT heparin binding at a single protein site with diverse side chain
RT interactions.";
RL Biochemistry 46:9941-9952(2007).
RN [10]
RP STRUCTURE BY NMR OF 22-81, AND DISULFIDE BONDS.
RX PubMed=8046750; DOI=10.1006/jmbi.1994.1460;
RA Jahnke W., Mierke D.F., Beress L., Kessler H.;
RT "Structure of cobra cardiotoxin CTX I as derived from nuclear magnetic
RT resonance spectroscopy and distance geometry calculations.";
RL J. Mol. Biol. 240:445-458(1994).
CC -!- FUNCTION: Basic protein that binds to cell membrane and depolarizes
CC cardiomyocytes. It also shows lytic activities on many other cells,
CC including red blood cells. Interaction with sulfatides in the cell
CC membrane induces pore formation and cell internalization and is
CC responsible for cytotoxicity in cardiomyocytes. It targets the
CC mitochondrial membrane and induces mitochondrial swelling and
CC fragmentation (By similarity). It binds to the integrin alpha-V/beta-3
CC (ITGAV/ITGB3) with a moderate affinity and inhibits protein kinases C
CC (PubMed:8448165). It also binds with high affinity to heparin
CC (PubMed:17685633). It also causes skeletal muscle necrosis after
CC intramuscular injection into mice (PubMed:8342169).
CC {ECO:0000250|UniProtKB:P01443, ECO:0000250|UniProtKB:P60301,
CC ECO:0000269|PubMed:8342169, ECO:0000269|PubMed:8448165}.
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:1147930}. Target
CC cell membrane {ECO:0000250|UniProtKB:P60301}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
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}.
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DR EMBL; Z54226; CAA90962.1; -; mRNA.
DR EMBL; U42583; AAB01539.1; -; mRNA.
DR EMBL; AJ238736; CAB42056.1; -; Genomic_DNA.
DR PIR; JC4619; H3NJ1F.
DR PDB; 2CDX; NMR; -; A=22-81.
DR PDBsum; 2CDX; -.
DR AlphaFoldDB; P60304; -.
DR SMR; P60304; -.
DR EvolutionaryTrace; P60304; -.
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; Myotoxin; Secreted; Signal;
KW Target cell membrane; Target membrane; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:1147930,
FT ECO:0000269|PubMed:8448165"
FT CHAIN 22..81
FT /note="Cytotoxin 1"
FT /evidence="ECO:0000269|PubMed:1147930,
FT ECO:0000269|PubMed:8448165"
FT /id="PRO_0000035365"
FT DISULFID 24..42
FT /evidence="ECO:0000269|PubMed:8046750,
FT ECO:0000312|PDB:2CDX"
FT DISULFID 35..59
FT /evidence="ECO:0000269|PubMed:8046750,
FT ECO:0000312|PDB:2CDX"
FT DISULFID 63..74
FT /evidence="ECO:0000269|PubMed:8046750,
FT ECO:0000312|PDB:2CDX"
FT DISULFID 75..80
FT /evidence="ECO:0000269|PubMed:8046750,
FT ECO:0000312|PDB:2CDX"
FT CONFLICT 10
FT /note="V -> L (in Ref. 3; CAB42056)"
FT /evidence="ECO:0000305"
FT CONFLICT 66..67
FT /note="NS -> SN (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 78
FT /note="D -> H (in Ref. 1; CAA90962)"
FT /evidence="ECO:0000305"
FT STRAND 27..30
FT /evidence="ECO:0007829|PDB:2CDX"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:2CDX"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:2CDX"
FT STRAND 55..62
FT /evidence="ECO:0007829|PDB:2CDX"
FT STRAND 71..77
FT /evidence="ECO:0007829|PDB:2CDX"
SQ SEQUENCE 81 AA; 8992 MW; 19C53E88D2E2596D CRC64;
MKTLLLTLVV VTIVCLDLGY TLKCNKLIPI ASKTCPAGKN LCYKMFMMSD LTIPVKRGCI
DVCPKNSLLV KYVCCNTDRC N
