3SOF5_NAJAT
ID 3SOF5_NAJAT Reviewed; 83 AA.
AC P62375; P14554;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 77.
DE RecName: Full=Cytotoxin A5 {ECO:0000305};
DE AltName: Full=CTX A5 {ECO:0000303|PubMed:8182052};
DE Short=CT A5 {ECO:0000303|PubMed:14743531};
DE AltName: Full=Cardiotoxin A5 {ECO:0000303|PubMed:14743531, ECO:0000303|PubMed:8182052};
DE AltName: Full=Cardiotoxin V {ECO:0000303|PubMed:8347605};
DE Short=CTX V;
DE Short=CTXV;
DE AltName: Full=Cardiotoxin-like basic polypeptide {ECO:0000303|PubMed:4091854};
DE Short=CLBP {ECO:0000303|PubMed:4091854};
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=8679666; DOI=10.1016/0167-4838(96)00047-7;
RA Chang L.-S., Lin J., Wu P.F.;
RT "cDNA sequence analysis and expression of cardiotoxin V and a new
RT cardiotoxin VII from Naja naja atra (Taiwan cobra).";
RL Biochim. Biophys. Acta 1295:1-4(1996).
RN [2]
RP PRELIMINARY PROTEIN SEQUENCE OF 22-83, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=4091854;
RA Takechi M., Tanaka Y., Hayashi K.;
RT "Amino acid sequence of a cardiotoxin-like basic polypeptide (CLBP) with
RT low cytotoxic activity isolated from the venom of the Formosan cobra (Naja
RT naja atra).";
RL Biochem. Int. 11:795-802(1985).
RN [3]
RP FUNCTION, AND P-TYPE CYTOTOXIN GROUP MISASSIGNATION.
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 [4]
RP FUNCTION, AND INACTIVATION BY ACIDIC PH.
RX PubMed=8703922; DOI=10.1021/bi952823k;
RA Chiang C.-M., Chien K.-Y., Lin H.-J., Lin J.-F., Yeh H.-C., Ho P.-L.,
RA Wu W.-G.;
RT "Conformational change and inactivation of membrane phospholipid-related
RT activity of cardiotoxin V from Taiwan cobra venom at acidic pH.";
RL Biochemistry 35:9167-9176(1996).
RN [5]
RP ROLE OF ACIDIC AMINO ACID RESIDUES.
RX PubMed=8703923; DOI=10.1021/bi960077t;
RA Chiang C.-M., Chang S.-L., Lin H.-J., Wu W.-G.;
RT "The role of acidic amino acid residues in the structural stability of
RT snake cardiotoxins.";
RL Biochemistry 35:9177-9186(1996).
RN [6]
RP FUNCTION.
RX PubMed=14743531; DOI=10.1023/b:rubi.0000008892.75272.ab;
RA Konshina A.G., Volynskii P.E., Arsen'ev A.S., Efremov R.G.;
RT "Interaction of cardiotoxin A5 with a membrane: role of conformational
RT heterogeneity and hydrophilic properties.";
RL Bioorg. Khim. 29:577-588(2003).
RN [7]
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 [8]
RP STRUCTURE BY NMR OF 22-83, AND DISULFIDE BONDS.
RX PubMed=8347605; DOI=10.1021/bi00082a026;
RA Singhal A.K., Chien K.-Y., Wu W.-G., Rule G.S.;
RT "Solution structure of cardiotoxin V from Naja naja atra.";
RL Biochemistry 32:8036-8044(1993).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) OF 22-83, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=9054545; DOI=10.1021/bi962594h;
RA Sun Y.-J., Wu W.-G., Chiang C.-M., Hsin A.-Y., Hsiao C.-D.;
RT "Crystal structure of cardiotoxin V from Taiwan cobra venom: pH-dependent
RT conformational change and a novel membrane-binding motif identified in the
RT three-finger loops of P-type cardiotoxin.";
RL Biochemistry 36:2403-2413(1997).
CC -!- FUNCTION: Non-cytotoxic protein that does not show lytic and hemolytic
CC activities, but can induce aggregation and fusion of sphingomyelin
CC vesicles (PubMed:8182052). It binds to integrin alpha-V/beta-3
CC (ITGAV/ITGB3) with high affinity, and it inhibits osteoclast
CC differentiation and bone resorption in mice, probably due to binding to
CC integrin alpha-V/beta-3 (PubMed:16407244).
CC {ECO:0000269|PubMed:14743531, ECO:0000269|PubMed:16407244,
CC ECO:0000269|PubMed:8182052, ECO:0000269|PubMed:8703922}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:4091854}. Target
CC cell membrane {ECO:0000269|PubMed:8703922}.
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 52 (Pro-31 in standard classification).
CC {ECO:0000305|PubMed:8182052}.
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain
CC subfamily. Orphan group XV sub-subfamily. {ECO:0000305}.
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DR EMBL; Z54228; CAA90964.1; -; mRNA.
DR PDB; 1CVO; NMR; -; A=22-83.
DR PDB; 1KXI; X-ray; 2.19 A; A/B=22-83.
DR PDBsum; 1CVO; -.
DR PDBsum; 1KXI; -.
DR AlphaFoldDB; P62375; -.
DR BMRB; P62375; -.
DR SMR; P62375; -.
DR EvolutionaryTrace; P62375; -.
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 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 InterPro; IPR035076; Toxin/TOLIP.
DR Pfam; PF00087; Toxin_TOLIP; 1.
DR PRINTS; PR00282; CYTOTOXIN.
DR SUPFAM; SSF57302; SSF57302; 1.
DR PROSITE; PS00272; SNAKE_TOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Membrane;
KW Secreted; Signal; Target cell membrane; Target membrane; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:4091854"
FT CHAIN 22..83
FT /note="Cytotoxin A5"
FT /evidence="ECO:0000305|PubMed:4091854"
FT /id="PRO_0000035404"
FT DISULFID 24..43
FT /evidence="ECO:0000269|PubMed:8347605,
FT ECO:0000269|PubMed:9054545, ECO:0007744|PDB:1CVO,
FT ECO:0007744|PDB:1KXI"
FT DISULFID 36..61
FT /evidence="ECO:0000269|PubMed:8347605,
FT ECO:0000269|PubMed:9054545, ECO:0007744|PDB:1CVO,
FT ECO:0007744|PDB:1KXI"
FT DISULFID 65..76
FT /evidence="ECO:0000269|PubMed:8347605,
FT ECO:0000269|PubMed:9054545, ECO:0007744|PDB:1CVO,
FT ECO:0007744|PDB:1KXI"
FT DISULFID 77..82
FT /evidence="ECO:0000269|PubMed:8347605,
FT ECO:0000269|PubMed:9054545, ECO:0007744|PDB:1CVO,
FT ECO:0007744|PDB:1KXI"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:1KXI"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:1KXI"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:1KXI"
FT STRAND 42..51
FT /evidence="ECO:0007829|PDB:1KXI"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:1KXI"
FT STRAND 70..77
FT /evidence="ECO:0007829|PDB:1KXI"
SQ SEQUENCE 83 AA; 9323 MW; 5FA396A4808D5099 CRC64;
MKTLLLTMVV VTIVCLDLGY TLKCHNTQLP FIYKTCPEGK NLCFKATLKK FPLKFPVKRG
CADNCPKNSA LLKYVCCSTD KCN
