3SA1_NAJPA
ID 3SA1_NAJPA Reviewed; 60 AA.
AC P01468;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Cytotoxin 1;
DE Short=CTX-1 {ECO:0000303|PubMed:2513886};
DE AltName: Full=Cardiotoxin gamma {ECO:0000303|PubMed:8196041};
OS Naja pallida (Red spitting cobra).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX NCBI_TaxID=8658;
RN [1]
RP PROTEIN SEQUENCE, DISULFIDE BONDS, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=1148181; DOI=10.1021/bi00684a012;
RA Fryklund L., Eaker D.;
RT "The complete covalent structure of a cardiotoxin from the venom of Naja
RT nigricollis (African black-necked spitting cobra).";
RL Biochemistry 14:2865-2871(1975).
RN [2]
RP PROTEIN SEQUENCE, AND IMPORTANCE OF LYS RESIDUES.
RC TISSUE=Venom;
RX PubMed=2513886; DOI=10.1021/bi00449a037;
RA Kini R.M., Evans H.J.;
RT "Role of cationic residues in cytolytic activity: modification of lysine
RT residues in the cardiotoxin from Naja nigricollis venom and correlation
RT between cytolytic and antiplatelet activity.";
RL Biochemistry 28:9209-9215(1989).
RN [3]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=8241426; DOI=10.1002/bip.360331104;
RA Gilquin B., Roumestand C., Zinn-Justin S., Menez A., Toma F.;
RT "Refined three-dimensional solution structure of a snake cardiotoxin:
RT analysis of the side-chain organization suggests the existence of a
RT possible phospholipid binding site.";
RL Biopolymers 33:1659-1675(1993).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS), AND DISULFIDE BONDS.
RX PubMed=8196041; DOI=10.1006/jmbi.1994.1357;
RA Bilwes A., Rees B., Moras D., Menez R., Menez A.;
RT "X-ray structure at 1.55 A of toxin gamma, a cardiotoxin from Naja
RT nigricollis venom. Crystal packing reveals a model for insertion into
RT membranes.";
RL J. Mol. Biol. 239:122-136(1994).
RN [5]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=7601102; DOI=10.1111/j.1432-1033.1995.tb20553.x;
RA Dauplais M., Neumann J.M., Pinkasfeld S., Menez A., Roumestand C.;
RT "An NMR study of the interaction of cardiotoxin gamma from Naja nigricollis
RT with perdeuterated dodecylphosphocholine micelles.";
RL Eur. J. Biochem. 230:213-220(1995).
CC -!- FUNCTION: Basic protein that binds to cell membrane and depolarizes
CC cardiomyocytes. This cytotoxin also possesses lytic activity 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. It binds to the integrin
CC alpha-V/beta-3 with a moderate affinity.
CC {ECO:0000250|UniProtKB:P01443}.
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:1148181}. Target
CC cell membrane {ECO:0000250|UniProtKB:P60301}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC -!- MISCELLANEOUS: Positive charges of Lys residues are necessary for
CC cytolytic activity of this toxin, but not for its binding ability.
CC {ECO:0000269|PubMed:2513886}.
CC -!- MISCELLANEOUS: Is classified as a P-type cytotoxin, since a proline
CC residue stands at position 30 (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}.
CC -!- CAUTION: The venom of this snake was originally thought to be that of
CC N.nigricollis while it is really from N.pallida. {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 PIR; A37578; H3NJ1B.
DR PDB; 1CXN; NMR; -; A=1-60.
DR PDB; 1CXO; NMR; -; A=1-60.
DR PDB; 1TGX; X-ray; 1.55 A; A/B/C=1-60.
DR PDBsum; 1CXN; -.
DR PDBsum; 1CXO; -.
DR PDBsum; 1TGX; -.
DR AlphaFoldDB; P01468; -.
DR SMR; P01468; -.
DR PRIDE; P01468; -.
DR EvolutionaryTrace; P01468; -.
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; Target cell membrane;
KW Target membrane; Toxin.
FT CHAIN 1..60
FT /note="Cytotoxin 1"
FT /evidence="ECO:0000269|PubMed:1148181,
FT ECO:0000269|PubMed:2513886"
FT /id="PRO_0000093519"
FT DISULFID 3..21
FT /evidence="ECO:0000269|PubMed:1148181,
FT ECO:0000269|PubMed:7601102, ECO:0000269|PubMed:8196041,
FT ECO:0000269|PubMed:8241426, ECO:0000312|PDB:1CXN,
FT ECO:0000312|PDB:1CXO, ECO:0000312|PDB:1TGX"
FT DISULFID 14..38
FT /evidence="ECO:0000269|PubMed:1148181,
FT ECO:0000269|PubMed:7601102, ECO:0000269|PubMed:8196041,
FT ECO:0000269|PubMed:8241426, ECO:0000312|PDB:1CXN,
FT ECO:0000312|PDB:1CXO, ECO:0000312|PDB:1TGX"
FT DISULFID 42..53
FT /evidence="ECO:0000269|PubMed:1148181,
FT ECO:0000269|PubMed:7601102, ECO:0000269|PubMed:8196041,
FT ECO:0000269|PubMed:8241426, ECO:0000312|PDB:1CXN,
FT ECO:0000312|PDB:1CXO, ECO:0000312|PDB:1TGX"
FT DISULFID 54..59
FT /evidence="ECO:0000269|PubMed:1148181,
FT ECO:0000269|PubMed:7601102, ECO:0000269|PubMed:8196041,
FT ECO:0000269|PubMed:8241426, ECO:0000312|PDB:1CXN,
FT ECO:0000312|PDB:1CXO, ECO:0000312|PDB:1TGX"
FT STRAND 2..4
FT /evidence="ECO:0007829|PDB:1TGX"
FT STRAND 6..9
FT /evidence="ECO:0007829|PDB:1CXN"
FT STRAND 10..13
FT /evidence="ECO:0007829|PDB:1TGX"
FT STRAND 20..26
FT /evidence="ECO:0007829|PDB:1TGX"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:1TGX"
FT STRAND 47..54
FT /evidence="ECO:0007829|PDB:1TGX"
SQ SEQUENCE 60 AA; 6827 MW; 68BE50B996B6491C CRC64;
LKCNQLIPPF WKTCPKGKNL CYKMTMRAAP MVPVKRGCID VCPKSSLLIK YMCCNTDKCN
