3L21_LATSE
ID 3L21_LATSE Reviewed; 87 AA.
AC P01379; O93496; Q7T2I4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 15-NOV-2002, sequence version 2.
DT 25-MAY-2022, entry version 121.
DE RecName: Full=Alpha-elapitoxin-Ls2a;
DE Short=Alpha-EPTX-Ls2a;
DE AltName: Full=Long neurotoxin Ls3;
DE AltName: Full=LsIII {ECO:0000303|PubMed:4616684, ECO:0000303|PubMed:8555211};
DE Short=Ls III {ECO:0000303|PubMed:26221036};
DE AltName: Full=Neurotoxin 1;
DE AltName: Full=Neurotoxin alpha;
DE Flags: Precursor;
OS Laticauda semifasciata (Black-banded sea krait) (Pseudolaticauda
OS semifasciata).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Laticaudinae; Laticauda.
OX NCBI_TaxID=8631;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LSIII-5 LYS-40.
RC TISSUE=Venom gland;
RX PubMed=9920490; DOI=10.1016/s0041-0101(98)00181-0;
RA Tamiya T., Ohno S., Nishimura E., Fujimi T.J., Tsuchiya T.;
RT "Complete nucleotide sequences of cDNAs encoding long chain alpha-
RT neurotoxins from sea krait, Laticauda semifasciata.";
RL Toxicon 37:181-185(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12957382; DOI=10.1016/s0378-1119(03)00637-1;
RA Fujimi T.J., Nakajyo T., Nishimura E., Ogura E., Tsuchiya T., Tamiya T.;
RT "Molecular evolution and diversification of snake toxin genes, revealed by
RT analysis of intron sequences.";
RL Gene 313:111-118(2003).
RN [3]
RP PROTEIN SEQUENCE OF 22-87, TOXIC DOSE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=4616684; DOI=10.1042/bj1410389;
RA Maeda N., Tamiya N.;
RT "The primary structure of the toxin Laticauda semifasciata III, a weak and
RT reversibly acting neurotoxin from the venom of a sea snake, Laticauda
RT semifasciata.";
RL Biochem. J. 141:389-400(1974).
RN [4]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=9305882; DOI=10.1074/jbc.272.39.24279;
RA Servent D., Winckler-Dietrich V., Hu H.-Y., Kessler P., Drevet P.,
RA Bertrand D., Menez A.;
RT "Only snake curaremimetic toxins with a fifth disulfide bond have high
RT affinity for the neuronal alpha7 nicotinic receptor.";
RL J. Biol. Chem. 272:24279-24286(1997).
RN [5]
RP FUNCTION.
RX PubMed=26221036; DOI=10.1074/jbc.m115.648824;
RA Kudryavtsev D.S., Shelukhina I.V., Son L.V., Ojomoko L.O., Kryukova E.V.,
RA Lyukmanova E.N., Zhmak M.N., Dolgikh D.A., Ivanov I.A., Kasheverov I.E.,
RA Starkov V.G., Ramerstorfer J., Sieghart W., Tsetlin V.I., Utkin Y.N.;
RT "Neurotoxins from snake venoms and alpha-conotoxin ImI inhibit functionally
RT active ionotropic gamma-aminobutyric acid (GABA) receptors.";
RL J. Biol. Chem. 290:22747-22758(2015).
RN [6]
RP STRUCTURE BY NMR OF 22-87, AND DISULFIDE BONDS.
RX PubMed=8555211; DOI=10.1021/bi9520287;
RA Connolly P.J., Stern A.S., Hoch J.C.;
RT "Solution structure of LSIII, a long neurotoxin from the venom of Laticauda
RT semifasciata.";
RL Biochemistry 35:418-426(1996).
CC -!- FUNCTION: Binds with high affinity to muscular (tested on Torpedo
CC marmorata, Kd=1.6 nM) and neuronal (chimeric alpha-7/CHRNA7, Kd=3 nM)
CC nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine
CC from binding to the receptor, thereby impairing neuromuscular and
CC neuronal transmission (PubMed:9305882). Also shows a very weak
CC inhibition on GABA(A) receptors (PubMed:26221036). The toxin (10 uM)
CC inhibits 83% of current in channels composed of alpha-1-beta-3-gamma-2
CC (GABRA1-GABRB3-GABRG2) subunits, 39% of current in channels composed of
CC alpha-2-beta-2-gamma-2 (GABRA2-GABRB2-GABRG2) subunits, and 33% of
CC current in channels composed of alpha-5-beta-2-gamma-2 (GABRA5-GABRB2-
CC GABRG2) subunits (PubMed:26221036). {ECO:0000269|PubMed:26221036,
CC ECO:0000269|PubMed:9305882}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:4616684}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:4616684}.
CC -!- TOXIC DOSE: LD(50) is 1.24 mg/kg by intramuscular injection.
CC {ECO:0000269|PubMed:4616684}.
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Long-chain
CC subfamily. Type II alpha-neurotoxin sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC78204.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB015512; BAA32991.1; -; mRNA.
DR EMBL; AB015513; BAA32992.1; -; mRNA.
DR EMBL; AB098531; BAC78204.1; ALT_FRAME; Genomic_DNA.
DR PDB; 1LSI; NMR; -; A=22-87.
DR PDBsum; 1LSI; -.
DR AlphaFoldDB; P01379; -.
DR BMRB; P01379; -.
DR SMR; P01379; -.
DR EvolutionaryTrace; P01379; -.
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; Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:4616684"
FT CHAIN 22..87
FT /note="Alpha-elapitoxin-Ls2a"
FT /evidence="ECO:0000269|PubMed:4616684"
FT /id="PRO_0000035430"
FT DISULFID 24..41
FT /evidence="ECO:0000269|PubMed:8555211,
FT ECO:0000312|PDB:1LSI"
FT DISULFID 34..62
FT /evidence="ECO:0000269|PubMed:8555211,
FT ECO:0000312|PDB:1LSI"
FT DISULFID 47..51
FT /evidence="ECO:0000269|PubMed:8555211,
FT ECO:0000312|PDB:1LSI"
FT DISULFID 66..77
FT /evidence="ECO:0000269|PubMed:8555211,
FT ECO:0000312|PDB:1LSI"
FT DISULFID 78..83
FT /evidence="ECO:0000269|PubMed:8555211,
FT ECO:0000312|PDB:1LSI"
FT VARIANT 40
FT /note="I -> K (in LSIII-5)"
FT /evidence="ECO:0000269|PubMed:9920490"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:1LSI"
FT STRAND 40..45
FT /evidence="ECO:0007829|PDB:1LSI"
FT STRAND 59..65
FT /evidence="ECO:0007829|PDB:1LSI"
FT STRAND 74..80
FT /evidence="ECO:0007829|PDB:1LSI"
FT TURN 81..84
FT /evidence="ECO:0007829|PDB:1LSI"
SQ SEQUENCE 87 AA; 9551 MW; CECC71F4A25C50A4 CRC64;
MKTLLLTLVV VTIVCLDLGY TRECYLNPHD TQTCPSGQEI CYVKSWCNAW CSSRGKVLEF
GCAATCPSVN TGTEIKCCSA DKCNTYP
