3S1CB_NAJAT
ID 3S1CB_NAJAT Reviewed; 83 AA.
AC P60770; O13079; P01430; Q675L7; Q9DE57; Q9W6X0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 1.
DT 25-MAY-2022, entry version 91.
DE RecName: Full=Cobrotoxin {ECO:0000303|PubMed:9367842};
DE Short=CBT;
DE Short=CBTX {ECO:0000303|PubMed:9367842};
DE Short=CTX {ECO:0000303|PubMed:27840083};
DE AltName: Full=Atratoxin {ECO:0000303|PubMed:11976497, ECO:0000303|PubMed:15252034};
DE AltName: Full=Cobratide {ECO:0000303|PubMed:27840083};
DE AltName: Full=Short neurotoxin 1;
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=9367842; DOI=10.1006/bbrc.1997.7549;
RA Chang L.-S., Lin J., Chou Y.-C., Hong E.;
RT "Genomic structures of cardiotoxin 4 and cobrotoxin from Naja naja atra
RT (Taiwan cobra).";
RL Biochem. Biophys. Res. Commun. 239:756-762(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS OF GLU-59 AND LYS-68.
RC TISSUE=Venom gland;
RX PubMed=10512733; DOI=10.1006/bbrc.1999.1418;
RA Chang L.-S., Chen K.-C., Wu B.-N., Lin S.-K., Wu P.-F., Hong Y.-R.,
RA Yang C.-C.;
RT "Expression and mutagenesis studies of cobrotoxin from Taiwan cobra.";
RL Biochem. Biophys. Res. Commun. 263:652-656(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Venom gland;
RA Qin C., Zhiyong H., Yi G., Shengli Y.;
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 22-49 AND 69-83, AND
RP SEQUENCE REVISION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=15252034; DOI=10.1074/jbc.m403863200;
RA Lou X., Liu Q., Tu X., Wang J., Teng M., Niu L., Schuller D.J., Huang Q.,
RA Hao Q.;
RT "The atomic resolution crystal structure of atratoxin determined by single
RT wavelength anomalous diffraction phasing.";
RL J. Biol. Chem. 279:39094-39104(2004).
RN [6]
RP PROTEIN SEQUENCE OF 22-83, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=5820687; DOI=10.1016/0005-2795(69)90046-4;
RA Yang C.-C., Yang H.J., Huang J.S.;
RT "The amino acid sequence of cobrotoxin.";
RL Biochim. Biophys. Acta 188:65-77(1969).
RN [7]
RP PROTEIN SEQUENCE OF 22-83.
RC TISSUE=Venom;
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 [8]
RP PROTEIN SEQUENCE OF 22-36, AND MASS SPECTROMETRY.
RX PubMed=11976497; DOI=10.1107/s0907444902002639;
RA Tu X., Huang Q., Lou X., Teng M., Niu L.;
RT "Purification, N-terminal sequencing, crystallization and preliminary X-ray
RT diffraction analysis of atratoxin, a new short-chain alpha-neurotoxin from
RT the venom of Naja naja atra.";
RL Acta Crystallogr. D 58:839-842(2002).
RN [9]
RP FUNCTION.
RX PubMed=9498573; DOI=10.1093/oxfordjournals.jbchem.a021889;
RA Chang L.-S., Chou Y.-C., Lin S.-R., Wu B.-N., Lin J., Hong E., Sun Y.-J.,
RA Hsiao C.-D.;
RT "A novel neurotoxin, cobrotoxin b, from Naja naja atra (Taiwan cobra)
RT venom: purification, characterization, and gene organization.";
RL J. Biochem. 122:1252-1259(1997).
RN [10]
RP DISULFIDE BONDS.
RX PubMed=5533659; DOI=10.1016/0005-2795(70)90013-9;
RA Yang C.-C., Yang H.J., Chiu R.H.C.;
RT "The position of disulfide bonds in cobrotoxin.";
RL Biochim. Biophys. Acta 214:355-363(1970).
RN [11]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=27840083; DOI=10.1016/j.jep.2016.11.009;
RA Zhu Q., Huang J., Wang S.Z., Qin Z.H., Lin F.;
RT "Cobrotoxin extracted from Naja atra venom relieves arthritis symptoms
RT through anti-inflammation and immunosuppression effects in rat arthritis
RT model.";
RL J. Ethnopharmacol. 194:1087-1095(2016).
RN [12]
RP PHARMACEUTICAL.
RX PubMed=32843715; DOI=10.1038/s41401-020-00501-7;
RA Lin F., Reid P.F., Qin Z.H.;
RT "Cobrotoxin could be an effective therapeutic for COVID-19.";
RL Acta Pharmacol. Sin. 41:1258-1260(2020).
RN [13]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=2249693; DOI=10.1111/j.1432-1033.1990.tb19401.x;
RA Yu C., Lee C.-S., Chuang L.-C., Shei Y.-R., Wang C.Y.;
RT "Two-dimensional NMR studies and secondary structure of cobrotoxin in
RT aqueous solution.";
RL Eur. J. Biochem. 193:789-799(1990).
RN [14]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=8443154; DOI=10.1021/bi00060a002;
RA Yu C., Bhaskaran R., Chuang L.-C., Yang C.-C.;
RT "Solution conformation of cobrotoxin: a nuclear magnetic resonance and
RT hybrid distance geometry-dynamical simulated annealing study.";
RL Biochemistry 32:2131-2136(1993).
CC -!- FUNCTION: Binds to muscle nicotinic acetylcholine receptor (nAChR) and
CC inhibit acetylcholine from binding to the receptor, thereby impairing
CC neuromuscular transmission. Has a higher toxicity than cobrotoxin-b
CC (PubMed:9498573). In vivo, when tested on rat arthritis models, shows
CC anti-inflammation and immunosuppression effects (PubMed:27840083).
CC {ECO:0000269|PubMed:27840083, ECO:0000269|PubMed:9498573}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:5820687}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=6952; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:11976497};
CC -!- TOXIC DOSE: LD(50) is 0.09 mg/kg by subcutaneous injection.
CC -!- PHARMACEUTICAL: Analgesic available under the trade name Cobratide
CC (approved by the National Medical Products Administration of China).
CC Has been safely used since 1978. {ECO:0000305|PubMed:27840083,
CC ECO:0000305|PubMed:32843715}.
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain
CC subfamily. Type I alpha-neurotoxin sub-subfamily. {ECO:0000305}.
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DR EMBL; U58519; AAB03221.1; -; mRNA.
DR EMBL; U58520; AAB03222.1; -; mRNA.
DR EMBL; U58521; AAB03223.1; -; mRNA.
DR EMBL; U77490; AAB36930.1; -; mRNA.
DR EMBL; U77491; AAB36931.1; -; mRNA.
DR EMBL; U77492; AAB36932.1; -; mRNA.
DR EMBL; U42582; AAB01538.1; -; mRNA.
DR EMBL; Y12492; CAA73097.2; -; Genomic_DNA.
DR EMBL; AF161797; AAG43384.1; -; Genomic_DNA.
DR EMBL; AJ239050; CAB43097.1; -; mRNA.
DR EMBL; AY471578; AAR33035.1; -; mRNA.
DR PIR; JC5769; N1NJ1F.
DR PDB; 1COE; NMR; -; A=22-83.
DR PDB; 1V6P; X-ray; 0.87 A; A/B=22-83.
DR PDBsum; 1COE; -.
DR PDBsum; 1V6P; -.
DR AlphaFoldDB; P60770; -.
DR BMRB; P60770; -.
DR SMR; P60770; -.
DR EvolutionaryTrace; P60770; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0099106; F:ion channel regulator activity; 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; IPR003571; Snake_3FTx.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR018354; Snake_toxin_con_site.
DR SUPFAM; SSF57302; SSF57302; 1.
DR PROSITE; PS00272; SNAKE_TOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylcholine receptor inhibiting toxin;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Pharmaceutical; Postsynaptic neurotoxin; Secreted; Signal;
KW Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:11976497,
FT ECO:0000269|PubMed:15252034, ECO:0000269|PubMed:5820687,
FT ECO:0000269|PubMed:8448165"
FT CHAIN 22..83
FT /note="Cobrotoxin"
FT /evidence="ECO:0000269|PubMed:5820687,
FT ECO:0000269|PubMed:8448165"
FT /id="PRO_0000035452"
FT SITE 54
FT /note="May be critical for toxicity"
FT SITE 57
FT /note="May be critical for toxicity"
FT DISULFID 24..45
FT /evidence="ECO:0000269|PubMed:2249693,
FT ECO:0000269|PubMed:8443154, ECO:0000312|PDB:1COE,
FT ECO:0000312|PDB:1V6P"
FT DISULFID 38..62
FT /evidence="ECO:0000269|PubMed:2249693,
FT ECO:0000269|PubMed:8443154, ECO:0000312|PDB:1COE,
FT ECO:0000312|PDB:1V6P"
FT DISULFID 64..75
FT /evidence="ECO:0000269|PubMed:2249693,
FT ECO:0000269|PubMed:8443154, ECO:0000312|PDB:1COE,
FT ECO:0000312|PDB:1V6P"
FT DISULFID 76..81
FT /evidence="ECO:0000269|PubMed:2249693,
FT ECO:0000269|PubMed:8443154, ECO:0000312|PDB:1COE,
FT ECO:0000312|PDB:1V6P"
FT MUTAGEN 59
FT /note="E->Q: Decrease in the rate of isomerization reaction
FT of disulfide bonds."
FT /evidence="ECO:0000269|PubMed:10512733"
FT MUTAGEN 68
FT /note="K->E: Decrease in the rate of isomerization reaction
FT of disulfide bonds."
FT /evidence="ECO:0000269|PubMed:10512733"
FT MUTAGEN 68
FT /note="K->Q: Decrease in the rate of isomerization reaction
FT of disulfide bonds."
FT /evidence="ECO:0000269|PubMed:10512733"
FT CONFLICT 2
FT /note="K -> E (in Ref. 4; AAG43384)"
FT /evidence="ECO:0000305"
FT CONFLICT 52
FT /note="D -> Y (in Ref. 3; CAB43097)"
FT /evidence="ECO:0000305"
FT CONFLICT 66
FT /note="S -> I (in Ref. 4; AAG43384)"
FT /evidence="ECO:0000305"
FT CONFLICT 73
FT /note="I -> S (in Ref. 4; AAG43384)"
FT /evidence="ECO:0000305"
FT CONFLICT 79..80
FT /note="DR -> G (in Ref. 3; CAB43097)"
FT /evidence="ECO:0000305"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:1V6P"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:1V6P"
FT STRAND 45..52
FT /evidence="ECO:0007829|PDB:1V6P"
FT STRAND 55..63
FT /evidence="ECO:0007829|PDB:1V6P"
FT STRAND 72..78
FT /evidence="ECO:0007829|PDB:1V6P"
SQ SEQUENCE 83 AA; 9262 MW; 4DD6077C92717052 CRC64;
MKTLLLTLLV VTIVCLDLGY TLECHNQQSS QTPTTTGCSG GETNCYKKRW RDHRGYRTER
GCGCPSVKNG IEINCCTTDR CNN
