CA1A_CONLI
ID CA1A_CONLI Reviewed; 37 AA.
AC L8BU87;
DT 03-SEP-2014, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 1.
DT 25-MAY-2022, entry version 33.
DE RecName: Full=Alpha-conotoxin LvIA {ECO:0000303|PubMed:24398291, ECO:0000303|PubMed:26742048};
DE Short=Alpha-CTx LvIA {ECO:0000303|PubMed:24398291, ECO:0000303|PubMed:26742048};
DE Flags: Precursor; Fragment;
OS Conus lividus (Livid cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Lividoconus.
OX NCBI_TaxID=89426;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SYNTHESIS OF 21-36, AMIDATION AT CYS-36,
RP FUNCTION, STRUCTURE BY NMR OF 21-36, AND SITE ASP-31.
RC TISSUE=Venom duct;
RX PubMed=24398291; DOI=10.1096/fj.13-244103;
RA Luo S., Zhangsun D., Schroeder C.I., Zhu X., Hu Y., Wu Y., Weltzin M.M.,
RA Eberhard S., Kaas Q., Craik D.J., McIntosh J.M., Whiteaker P.;
RT "A novel alpha4/7-conotoxin LvIA from Conus lividus that selectively blocks
RT alpha3beta2 vs. alpha6/alpha3beta2beta3 nicotinic acetylcholine
RT receptors.";
RL FASEB J. 28:1842-1853(2014).
RN [2]
RP FUNCTION, AND BIOASSAY.
RX PubMed=26742048; DOI=10.3390/md14010011;
RA Zhu X., Bi J., Yu J., Li X., Zhang Y., Zhangsun D., Luo S.;
RT "Recombinant expression and characterization of alpha-Conotoxin LvIA in
RT Escherichia coli.";
RL Mar. Drugs 14:11-25(2016).
RN [3]
RP MUTAGENESIS OF 29-ASN-VAL-30, AND SYNTHESIS OF 21-36.
RX PubMed=26330550; DOI=10.1124/mol.115.100982;
RA Hone A.J., McIntosh J.M., Azam L., Lindstrom J., Lucero L., Whiteaker P.,
RA Passas J., Blazquez J., Albillos A.;
RT "Alpha-conotoxins identify the alpha3beta4* subtype as the predominant
RT nicotinic acetylcholine receptor expressed in human adrenal chromaffin
RT cells.";
RL Mol. Pharmacol. 88:881-893(2015).
RN [4]
RP ERRATUM OF PUBMED:26330550.
RX PubMed=26783122; DOI=10.1124/mol.115.100982err;
RA Hone A.J., McIntosh J.M., Azam L., Lindstrom J., Lucero L., Whiteaker P.,
RA Passas J., Blazquez J., Albillos A.;
RT "Correction to 'alpha-conotoxins identify the alpha3beta4* subtype as the
RT predominant nicotinic acetylcholine receptor expressed in human adrenal
RT chromaffin cells'.";
RL Mol. Pharmacol. 89:322-322(2016).
CC -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC This toxin blocks alpha-3-beta-2/CHRNA3-CHRNB2 nAChR with high
CC selectivity (IC(50)=8.67 nM (on rat) and 17.5 (on human))
CC (PubMed:24398291). Has also weaker activity on alpha-6/alpha-3-beta-2-
CC beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) (IC(50)=108 nM (on rat)), alpha-
CC 6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) (IC(50)=121 nM (on rat)),
CC alpha-3-beta-4 (CHRNA3-CHRNB4) (IC(50)=148 nM (on rat)), and alpha-
CC 7/CHRNA7 nAChRs (IC(50)=3000 nM (on rat)) (PubMed:24398291). When
CC tested on mouse with hot-plate tests, this toxin significantly
CC increases the base pain threshold and shows analgesic effects
CC (PubMed:26742048). {ECO:0000269|PubMed:24398291,
CC ECO:0000269|PubMed:26742048}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P85013}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: Does not block alpha-9-alpha-10/CHRNA9-CHRNA10, alpha-2-
CC beta-2/CHRNA2-CHRNB2, alpha-2-beta-4/CHRNA2-CHRNB4, alpha-3-beta-
CC 4/CHRNA3-CHRNB4, alpha-4-beta-2/CHRNA4-CHRNB2, alpha-4-beta-4/CHRNA4-
CC CHRNB4, alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3),
CC alpha-6-beta-4/CHRNA6-CHRNB4, and alpha-1-beta-1-epsilon-delta/CHRNA1-
CC CHRNB1-CHRNE-CHRND. {ECO:0000269|PubMed:24398291,
CC ECO:0000269|PubMed:26742048}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR EMBL; HF566436; CCP46959.1; -; Genomic_DNA.
DR PDB; 2MDQ; NMR; -; A=21-36.
DR PDB; 5XGL; X-ray; 3.44 A; C/E/F/H/J=21-36.
DR PDB; 6M4X; X-ray; 3.00 A; C/E/F/H/J=21-36.
DR PDB; 6M4Z; X-ray; 2.80 A; C/E/F/H/J=21-36.
DR PDBsum; 2MDQ; -.
DR PDBsum; 5XGL; -.
DR PDBsum; 6M4X; -.
DR PDBsum; 6M4Z; -.
DR AlphaFoldDB; L8BU87; -.
DR BMRB; L8BU87; -.
DR SMR; L8BU87; -.
DR TCDB; 8.B.32.1.4; the nicotinic acetylcholine receptor-targeting alpha-conotoxin (a-conotoxin) family.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
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 InterPro; IPR009958; Conotoxin_a-typ.
DR InterPro; IPR018072; Conotoxin_a-typ_CS.
DR Pfam; PF07365; Toxin_8; 1.
DR PROSITE; PS60014; ALPHA_CONOTOXIN; 1.
PE 3: Inferred from homology;
KW 3D-structure; Acetylcholine receptor inhibiting toxin; Amidation;
KW Cleavage on pair of basic residues; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Postsynaptic neurotoxin; Secreted;
KW Toxin.
FT PROPEP <1..20
FT /evidence="ECO:0000250"
FT /id="PRO_0000430172"
FT PEPTIDE 21..36
FT /note="Alpha-conotoxin LvIA"
FT /evidence="ECO:0000305|PubMed:24398291"
FT /id="PRO_0000430173"
FT REGION 24..26
FT /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT with nAChR"
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT SITE 31
FT /note="May play a crucial role for the selectivity for
FT alpha-3-beta-2 nAChR"
FT /evidence="ECO:0000305|PubMed:24398291"
FT MOD_RES 36
FT /note="Cysteine amide"
FT /evidence="ECO:0000305|PubMed:24398291"
FT DISULFID 22..28
FT /evidence="ECO:0000305|PubMed:24398291,
FT ECO:0007744|PDB:2MDQ"
FT DISULFID 23..36
FT /evidence="ECO:0000305|PubMed:24398291,
FT ECO:0007744|PDB:2MDQ"
FT MUTAGEN 29..30
FT /note="NV->RA: Shows inhibition on alpha-3-beta-2
FT (IC(50)=3.3 nM), beta-3-alpha-6-beta-2-alpha-4-beta-2
FT (IC(50)=11.4 nM), alpha-6/alpha-3-beta-2-beta-3
FT (IC(50)=13.5 nM), alpha-4-beta-2 (IC(50)=195 nM), alpha-
FT 6/alpha-3-beta-4 (IC(50)=1000 nM) nAChRs. Does not inhibit
FT alpha-3-beta-4, beta-4-alpha-3-beta-4-alpha-3-alpha-5, and
FT alpha-4-beta-4 nAChRs."
FT /evidence="ECO:0000269|PubMed:26330550"
FT NON_TER 1
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:6M4X"
FT HELIX 26..31
FT /evidence="ECO:0007829|PDB:6M4Z"
FT TURN 33..35
FT /evidence="ECO:0007829|PDB:6M4Z"
SQ SEQUENCE 37 AA; 3841 MW; B5501D068E48873C CRC64;
FRGRDAAAKA SGLVGLTDRR GCCSHPACNV DHPEICG
