CA13B_CONLT
ID CA13B_CONLT Reviewed; 41 AA.
AC A0A068B0Z6;
DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2014, sequence version 1.
DT 25-MAY-2022, entry version 20.
DE RecName: Full=Alpha-conotoxin Lt1.3 b {ECO:0000303|PubMed:29614714, ECO:0000305};
DE Flags: Precursor; Fragment;
OS Conus litteratus (Lettered cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Elisaconus.
OX NCBI_TaxID=89445;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SYNTHESIS OF 22-37, AMIDATION
RP AT CYS-37, AND MUTAGENESIS OF SER-30; ASN-32; ASN-33; PRO-34; TYR-35 AND
RP PHE-36.
RX PubMed=29614714; DOI=10.3390/md16040112;
RA Chen J., Liang L., Ning H., Cai F., Liu Z., Zhang L., Zhou L., Dai Q.;
RT "Cloning, synthesis and functional characterization of a novel alpha-
RT conotoxin Lt1.3.";
RL Mar. Drugs 16:1-12(2018).
CC -!- FUNCTION: Lt1.3-II (C1-C3; C2-C4): Alpha-conotoxins act on postsynaptic
CC membranes, they bind to the nicotinic acetylcholine receptors (nAChR)
CC and thus inhibit them. This toxin potently and selectively inhibits
CC alpha-3-beta-2/CHRNA3-CHRNB2 (IC(50)=44.8 nM) nAChRs.
CC {ECO:0000269|PubMed:29614714}.
CC -!- FUNCTION: Lt1.3-I (C1-C4; C2-C3): This isomer inhibits GABABRec-coupled
CC Cav2.2/CACNA1B but has no activity on nAChRs.
CC {ECO:0000269|PubMed:29614714}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:29614714}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:29614714}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: Lt1.3-II (C1-C3; C2-C4): this synthetic toxin shows no
CC or very weak inhibition on alpha-2-beta-2/CHRNA2-CHRNB2, alpha-2-beta-
CC 4/CHRNA2-CHRNB4, alpha-3-beta-4/CHRNA3-CHRNB4, alpha-4-beta-2/CHRNA4-
CC CHRNB2, alpha-4-beta-4/CHRNA4-CHRNB4, alpha-7/CHRNA7, alpha-9-alpha-
CC 10/CHRNA9-CHRNA10, and GABAB-Rec-coupled Cav2.2/CACNA1B.
CC {ECO:0000269|PubMed:29614714}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
CC -!- CAUTION: This toxin has been called Lt1.3 b, since the name Lt1.3 is
CC already attributed to AC Q2I2R6. {ECO:0000305}.
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DR EMBL; KF414121; AIC77104.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A068B0Z6; -.
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:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR009958; Conotoxin_a-typ.
DR Pfam; PF07365; Toxin_8; 1.
PE 1: Evidence at protein level;
KW Acetylcholine receptor inhibiting toxin; Amidation;
KW Calcium channel impairing toxin; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Postsynaptic neurotoxin; Secreted;
KW Toxin; Voltage-gated calcium channel impairing toxin.
FT PROPEP <1..21
FT /evidence="ECO:0000305|PubMed:29614714"
FT /id="PRO_0000445012"
FT PEPTIDE 22..37
FT /note="Alpha-conotoxin Lt1.3 b"
FT /evidence="ECO:0000305|PubMed:29614714"
FT /id="PRO_0000445013"
FT PROPEP 38..41
FT /evidence="ECO:0000305|PubMed:29614714"
FT /id="PRO_0000445014"
FT REGION 25..27
FT /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT with nAChR"
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT MOD_RES 37
FT /note="Cysteine amide"
FT /evidence="ECO:0000305|PubMed:29614714"
FT DISULFID 23..37
FT /note="In Lt1.3-I (C1-C4; C2-C3); partial"
FT /evidence="ECO:0000305|PubMed:29614714"
FT DISULFID 23..29
FT /note="In Lt1.3-II (C1-C3; C2-C4); partial"
FT /evidence="ECO:0000305|PubMed:29614714"
FT DISULFID 24..37
FT /note="In Lt1.3-II (C1-C3; C2-C4); partial"
FT /evidence="ECO:0000305|PubMed:29614714"
FT DISULFID 24..29
FT /note="In Lt1.3-I (C1-C4; C2-C3); partial"
FT /evidence="ECO:0000305|PubMed:29614714"
FT MUTAGEN 30
FT /note="S->A: Small increase of inhibitory potency on alpha-
FT 3-beta-2/CHRNA3-CHRNB2 nAChR (Lt1.3-II)."
FT /evidence="ECO:0000269|PubMed:29614714"
FT MUTAGEN 32
FT /note="N->A: Loss of inhibitory potency on alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR (Lt1.3-II)."
FT /evidence="ECO:0000269|PubMed:29614714"
FT MUTAGEN 33
FT /note="N->A: Loss of inhibitory potency on alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR (Lt1.3-II)."
FT /evidence="ECO:0000269|PubMed:29614714"
FT MUTAGEN 34
FT /note="P->A: Loss of inhibitory potency on alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR (Lt1.3-II)."
FT /evidence="ECO:0000269|PubMed:29614714"
FT MUTAGEN 35
FT /note="Y->A: Important decrease of inhibitory potency on
FT alpha-3-beta-2/CHRNA3-CHRNB2 nAChR (Lt1.3-II)."
FT /evidence="ECO:0000269|PubMed:29614714"
FT MUTAGEN 36
FT /note="F->A: Loss of inhibitory potency on alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR (Lt1.3-II)."
FT /evidence="ECO:0000269|PubMed:29614714"
FT NON_TER 1
FT /evidence="ECO:0000312|EMBL:AIC77104.1"
SQ SEQUENCE 41 AA; 4244 MW; 080F4845F0E15D18 CRC64;
FDGRNAAPSD KASDLISLAV RGCCSHPACS GNNPYFCGGK R
