3L2A_BUNCA
ID 3L2A_BUNCA Reviewed; 95 AA.
AC Q7T3J2; Q8AY54;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 25-MAY-2022, entry version 79.
DE RecName: Full=Alpha-bungarotoxin, isoform A31 {ECO:0000305};
DE Short=Alpha-BgTx (A31) {ECO:0000303|PubMed:30944155};
DE Short=Alpha-bungarotoxin (A31) {ECO:0000303|PubMed:14505938, ECO:0000303|PubMed:30944155};
DE Flags: Precursor;
OS Bungarus candidus (Malayan krait).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Bungarinae; Bungarus.
OX NCBI_TaxID=92438;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RA Tsai I.H., Wang Y.M., Hsu H.Y.;
RT "Structural and functional genomics of Bungarus candidus.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-95, PROTEIN SEQUENCE OF 22-61,
RP FUNCTION, MASS SPECTROMETRY, TOXIC DOSE, AND SUBCELLULAR LOCATION.
RC TISSUE=Skin, and Venom;
RX PubMed=14505938; DOI=10.1016/s0041-0101(03)00168-5;
RA Kuch U., Molles B.E., Omori-Satoh T., Chanhome L., Samejima Y., Mebs D.;
RT "Identification of alpha-bungarotoxin (A31) as the major postsynaptic
RT neurotoxin, and complete nucleotide identity of a genomic DNA of Bungarus
RT candidus from Java with exons of the Bungarus multicinctus alpha-
RT bungarotoxin (A31) gene.";
RL Toxicon 42:381-390(2003).
RN [3]
RP FUNCTION, AND SYNTHESIS OF 22-95.
RX PubMed=30944155; DOI=10.1042/bcj20180909;
RA Utkin Y.N., Kuch U., Kasheverov I.E., Lebedev D.S., Cederlund E.,
RA Molles B.E., Polyak I., Ivanov I.A., Prokopev N.A., Ziganshin R.H.,
RA Jornvall H., Alvelius G., Chanhome L., Warrell D.A., Mebs D., Bergman T.,
RA Tsetlin V.I.;
RT "Novel long-chain neurotoxins from Bungarus candidus distinguish the two
RT binding sites in muscle-type nicotinic acetylcholine receptors.";
RL Biochem. J. 476:1285-1302(2019).
CC -!- FUNCTION: Binds with high affinity to muscular (tested on Torpedo
CC marmorata, Kd=0.4 nM) and neuronal (tested on chimeric alpha-7/CHRNA7,
CC Kd=0.95 nM) nicotinic acetylcholine receptor (nAChR) and inhibits
CC acetylcholine from binding to the receptor, thereby impairing
CC neuromuscular and neuronal transmission. It also shows an activity on
CC GABA(A) receptors. It antagonises GABA-activated currents with high
CC potency when tested on primary hippocampal neurons. It inhibits
CC recombinantly expressed GABA(A) receptors composed of alpha-2-beta-2-
CC gamma-2 (GABRA2-GABRB2-GABRG2) subunits with high potency (62.3%
CC inhibition at 20 uM of toxin). It also shows a weaker inhibition on
CC GABA(A) receptors composed of alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-
CC GABRG2) subunits, alpha-4-beta-2-gamma-2 (GABRA4-GABRB2-GABRG2)
CC subunits, and alpha-5-beta-2-gamma-2 (GABRA5-GABRB2-GABRG2) subunits. A
CC very weak inhibition is also observed on GABA(A) receptor composed of
CC alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2). It has also been shown
CC to bind and inhibit recombinant GABA(A) receptor beta-3/GABRB3 subunit
CC (Kd=about 50 nM). In addition, it blocks the extracellular increase of
CC dopamine evoked by nicotine only at the higher dose (4.2 uM). In vivo,
CC when intraperitoneally injected into mice, induces flaccid paralysis of
CC the limbs and respiratory distress, and causes death in a dose-
CC dependent manner (PubMed:14505938). {ECO:0000250|UniProtKB:P60615,
CC ECO:0000269|PubMed:14505938}.
CC -!- SUBUNIT: Monomer in solution, homodimer in crystal state.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14505938}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:14505938}.
CC -!- MASS SPECTROMETRY: Mass=7983.75; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:14505938};
CC -!- TOXIC DOSE: LD(50) is 230 ug/kg by intraperitoneal injection into mice.
CC {ECO:0000269|PubMed:14505938}.
CC -!- MISCELLANEOUS: Is identical to Alpha-bungarotoxin (A31) from
CC B.multicinctus (AC P60615). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Long-chain
CC subfamily. Type II alpha-neurotoxin sub-subfamily. {ECO:0000305}.
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DR EMBL; AY057874; AAL30056.1; -; mRNA.
DR EMBL; AJ565000; CAD92407.1; -; Genomic_DNA.
DR AlphaFoldDB; Q7T3J2; -.
DR BMRB; Q7T3J2; -.
DR SMR; Q7T3J2; -.
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 InterPro; IPR035076; Toxin/TOLIP.
DR Pfam; PF00087; Toxin_TOLIP; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
DR PROSITE; PS00272; SNAKE_TOXIN; 1.
PE 1: Evidence at protein level;
KW Acetylcholine receptor inhibiting toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:14505938"
FT CHAIN 22..95
FT /note="Alpha-bungarotoxin, isoform A31"
FT /id="PRO_0000035405"
FT DISULFID 24..44
FT /evidence="ECO:0000250|UniProtKB:P60615"
FT DISULFID 37..65
FT /evidence="ECO:0000250|UniProtKB:P60615"
FT DISULFID 50..54
FT /evidence="ECO:0000250|UniProtKB:P60615"
FT DISULFID 69..80
FT /evidence="ECO:0000250|UniProtKB:P60615"
FT DISULFID 81..86
FT /evidence="ECO:0000250|UniProtKB:P60615"
SQ SEQUENCE 95 AA; 10285 MW; 589B26743ABBA5E4 CRC64;
MKTLLLTLVV VTIVCLDLGY TIVCHTTATS PISAVTCPPG ENLCYRKMWC DAFCSSRGKV
VELGCAATCP SKKPYEEVTC CSTDKCNPHP KQRPG
