3SXA_MICFL
ID 3SXA_MICFL Reviewed; 84 AA.
AC U3FAE1;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Fulditoxin {ECO:0000303|PubMed:31877243};
DE AltName: Full=Micrurus fulvius dimeric neurotoxin {ECO:0000303|PubMed:31877243};
DE AltName: Full=SIGMA-neurotoxin {ECO:0000303|PubMed:31877243};
DE AltName: Full=Three-finger toxin 3a {ECO:0000312|EMBL:JAB52854.1};
DE Short=3FTx 3a {ECO:0000305};
DE AltName: Full=Three-finger toxin 9a {ECO:0000312|EMBL:JAI09079.1};
DE AltName: Full=Three-finger toxin 9d {ECO:0000312|EMBL:JAI09076.1};
DE AltName: Full=Three-finger toxin 9e {ECO:0000312|EMBL:JAI09075.1};
DE Flags: Precursor;
OS Micrurus fulvius (Eastern coral snake) (Coluber fulvius).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Micrurus.
OX NCBI_TaxID=8637;
RN [1] {ECO:0000312|EMBL:JAB52854.1, ECO:0000312|EMBL:JAI09075.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=23915248; DOI=10.1186/1471-2164-14-531;
RA Margres M.J., Aronow K., Loyacano J., Rokyta D.R.;
RT "The venom-gland transcriptome of the eastern coral snake (Micrurus
RT fulvius) reveals high venom complexity in the intragenomic evolution of
RT venoms.";
RL BMC Genomics 14:531-531(2013).
RN [2] {ECO:0000312|EMBL:JAS05064.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=26358130; DOI=10.1534/g3.115.020578;
RA Rokyta D.R., Margres M.J., Calvin K.;
RT "Post-transcriptional mechanisms contribute little to phenotypic variation
RT in snake venoms.";
RL G3 (Bethesda) 5:2375-2382(2015).
RN [3] {ECO:0007744|PDB:4RUD}
RP PROTEIN SEQUENCE OF 22-84, X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 22-79,
RP DISULFIDE BOND, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, MASS SPECTROMETRY,
RP AND SYNTHESIS OF 22-79.
RC TISSUE=Venom;
RX PubMed=31877243; DOI=10.1111/bph.14954;
RA Foo C.S., Jobichen C., Hassan-Puttaswamy V., Dekan Z., Tae H.S.,
RA Bertrand D., Adams D.J., Alewood P.F., Sivaraman J., Nirthanan S.,
RA Kini R.M.;
RT "Fulditoxin, representing a new class of dimeric snake toxins, defines
RT novel pharmacology at nicotinic ACh receptors.";
RL Br. J. Pharmacol. 177:1822-1840(2020).
CC -!- FUNCTION: Postsynaptic neurotoxin that produces potent, and completely
CC reversible, postsynaptic neuromuscular blockade, as well as broad
CC spectrum inhibition of human muscle and neuronal nicotinic
CC acetylcholine receptors (nAChRs). Inhibition is potent or moderate,
CC depending on the receptor (alpha-1-beta-1-delta-epsilon/CHRNA1-CHRNB1-
CC CHRND-CHRNE (IC(50)=2.56 uM), alpha-4-beta-2/CHRNA4-CHRNB2 (IC(50)=1.8
CC uM), alpha-7/CHRNA7 (IC(50)=7 uM), and alpha-3-beta-2/CHRNA3-CHRNB2
CC (IC(50)=12.6 uM)) (PubMed:31877243). Acts as a competitive antagonist
CC of ACh (PubMed:31877243). Binds to chicken muscle-type nicotinic
CC acetylcholine receptor (AChR) with high potency compared with the
CC cloned human receptor (PubMed:31877243). Unlike short-chain alpha-3FTxs
CC that only bind to muscle nAChRs, this toxin utilizes dimerization to
CC expand its pharmacological targets to block neuronal nAChRs
CC (PubMed:31877243). {ECO:0000269|PubMed:31877243}.
CC -!- SUBUNIT: Homodimer; non-covalently linked. Is able to form a tetramer
CC of dimers in the presence of 2 zinc ions.
CC {ECO:0000269|PubMed:31877243}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:31877243}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:23915248}.
CC -!- MASS SPECTROMETRY: Mass=6947.4; Method=Electrospray; Note=Only one
CC subunit.; Evidence={ECO:0000269|PubMed:31877243};
CC -!- MISCELLANEOUS: Weakly inhibits human alpha-4-beta-4/CHRNA4-CHRNB4 and
CC has no activity on human alpha-9-alpha-10/CHRNA9-CHRNA10 and human
CC alpha-3-beta-4/CHRNA3-CHRNB4 nAChRs. {ECO:0000269|PubMed:31877243}.
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain
CC subfamily. {ECO:0000305}.
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DR EMBL; GAEP01001967; JAB52854.1; -; mRNA.
DR EMBL; GBEW01001290; JAI09075.1; -; mRNA.
DR EMBL; GBEW01001289; JAI09076.1; -; mRNA.
DR EMBL; GBEW01001286; JAI09079.1; -; mRNA.
DR EMBL; GDBF01000022; JAS05064.1; -; Transcribed_RNA.
DR EMBL; GDBF01000021; JAS05065.1; -; Transcribed_RNA.
DR EMBL; GDBF01000018; JAS05068.1; -; Transcribed_RNA.
DR PDB; 4RUD; X-ray; 1.95 A; A/B=22-79.
DR PDBsum; 4RUD; -.
DR AlphaFoldDB; U3FAE1; -.
DR SMR; U3FAE1; -.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR SUPFAM; SSF57302; SSF57302; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylcholine receptor inhibiting toxin;
KW Direct protein sequencing; Disulfide bond; Metal-binding; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Signal; Toxin; Zinc.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:31877243"
FT CHAIN 22..84
FT /note="Fulditoxin"
FT /evidence="ECO:0000269|PubMed:31877243"
FT /id="PRO_0000452325"
FT BINDING 50
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:31877243,
FT ECO:0007744|PDB:4RUD"
FT SITE 58
FT /note="Contributes to dimerization"
FT /evidence="ECO:0000305|PubMed:31877243"
FT SITE 61
FT /note="Contributes to dimerization"
FT /evidence="ECO:0000305|PubMed:31877243"
FT SITE 64
FT /note="Contributes to dimerization"
FT /evidence="ECO:0000305|PubMed:31877243"
FT DISULFID 24..41
FT /evidence="ECO:0000269|PubMed:31877243,
FT ECO:0007744|PDB:4RUD"
FT DISULFID 34..59
FT /evidence="ECO:0000269|PubMed:31877243,
FT ECO:0007744|PDB:4RUD"
FT DISULFID 63..71
FT /evidence="ECO:0000269|PubMed:31877243,
FT ECO:0007744|PDB:4RUD"
FT DISULFID 72..77
FT /evidence="ECO:0000269|PubMed:31877243,
FT ECO:0007744|PDB:4RUD"
FT STRAND 23..29
FT /evidence="ECO:0007829|PDB:4RUD"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:4RUD"
FT STRAND 40..47
FT /evidence="ECO:0007829|PDB:4RUD"
FT STRAND 53..62
FT /evidence="ECO:0007829|PDB:4RUD"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:4RUD"
FT TURN 75..78
FT /evidence="ECO:0007829|PDB:4RUD"
SQ SEQUENCE 84 AA; 9183 MW; 2C6729F154394C49 CRC64;
MKTLLLTLVV VTIVCLDLGN SLKCYSSRTE TMTCPEGEDK CEKYAVGLMH GSFFFIYTCT
SKCHEGAYNV CCSTDLCNKS STSG
