CLE1_CONLT
ID CLE1_CONLT Reviewed; 64 AA.
AC Q2I2R5; Q0P0L5;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 25-MAY-2022, entry version 46.
DE RecName: Full=Alpha-conotoxin Lt14.1 {ECO:0000303|PubMed:16908117};
DE AltName: Full=Alpha-L-conotoxin Lt14a {ECO:0000303|PubMed:16797781, ECO:0000303|PubMed:16908117, ECO:0000303|PubMed:21126549, ECO:0000303|PubMed:25617597};
DE AltName: Full=Alpha-conotoxin LtXIVA {ECO:0000305};
DE Flags: Precursor;
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 [MRNA], SYNTHESIS OF 51-63, PROBABLE AMIDATION AT
RP CYS-63, AND FUNCTION.
RC TISSUE=Venom duct;
RX PubMed=16797781; DOI=10.1016/j.peptides.2006.04.016;
RA Peng C., Tang S., Pi C., Liu J., Wang F., Wang L., Zhou W., Xu A.;
RT "Discovery of a novel class of conotoxin from Conus litteratus, lt14a, with
RT a unique cysteine pattern.";
RL Peptides 27:2174-2181(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom duct;
RX PubMed=16908117; DOI=10.1016/j.ygeno.2006.06.014;
RA Pi C., Liu J., Peng C., Liu Y., Jiang X., Zhao Y., Tang S., Wang L.,
RA Dong M., Chen S., Xu A.;
RT "Diversity and evolution of conotoxins based on gene expression profiling
RT of Conus litteratus.";
RL Genomics 88:809-819(2006).
RN [3]
RP FUNCTION, SYNTHESIS OF 51-63, PROBABLE AMIDATION AT CYS-63, AND PROBABLE
RP DISULFIDE BOND.
RX PubMed=25617597; DOI=10.1016/j.toxicon.2015.01.013;
RA Ren Z., Wang L., Qin M., You Y., Pan W., Zhou L., Sun D., Xu A.;
RT "Pharmacological characterization of conotoxin lt14a as a potent non-
RT addictive analgesic.";
RL Toxicon 96:57-67(2015).
RN [4]
RP STRUCTURE BY NMR OF 51-63, SYNTHESIS OF 51-63, MUTAGENESIS OF LYS-57,
RP PROBABLE AMIDATION AT CYS-63, AND FUNCTION.
RX PubMed=21126549; DOI=10.1016/j.peptides.2010.11.012;
RA Sun D., Ren Z., Zeng X., You Y., Pan W., Zhou M., Wang L., Xu A.;
RT "Structure-function relationship of conotoxin lt14a, a potential analgesic
RT with low cytotoxicity.";
RL Peptides 32:300-305(2011).
CC -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC the nicotinic acetylcholine receptors (nAChR) and thus inhibit them
CC (PubMed:16797781, PubMed:25617597). This synthetic peptide displays
CC analgesic activity in a hot plate assay (PubMed:16797781,
CC PubMed:25617597, PubMed:21126549). Analgesia is also observed against
CC second phase pain in formalin-induced inflammatory pain model, and in a
CC rat model of mechanically-induced pain (PubMed:25617597). Effects
CC downstream of nAChR are inhibition of calcium influx, inhibition of
CC ERK1/2 phosphorylation and inhibition of c-fos/NOS expression
CC (PubMed:25617597). Genes associated with drug dependence are not up-
CC regulated by this toxin (PubMed:25617597). Treatment with this toxin
CC reversed morphine withdrawal symptoms in mice (PubMed:25617597).
CC {ECO:0000269|PubMed:16797781, ECO:0000269|PubMed:25617597}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct. {ECO:0000305}.
CC -!- DOMAIN: The cysteine framework is XIV (C-C-C-C). {ECO:0000305}.
CC -!- PTM: May contain a 4-hydroxyproline. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the conotoxin L superfamily. {ECO:0000305}.
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DR EMBL; DQ205654; ABA39796.1; -; mRNA.
DR EMBL; DQ345367; ABC74975.1; -; mRNA.
DR AlphaFoldDB; Q2I2R5; -.
DR TCDB; 8.B.32.1.11; the nicotinic acetylcholine receptor-targeting alpha-conotoxin (a-conotoxin) family.
DR ConoServer; 1153; lt14a variant precursor.
DR ConoServer; 27; LtXIVA precursor.
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.
PE 1: Evidence at protein level;
KW Acetylcholine receptor inhibiting toxin; Amidation; Disulfide bond;
KW Hydroxylation; Ion channel impairing toxin; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..50
FT /evidence="ECO:0000250"
FT /id="PRO_0000262666"
FT PEPTIDE 51..63
FT /note="Alpha-conotoxin Lt14.1"
FT /evidence="ECO:0000305|PubMed:16797781"
FT /id="PRO_0000262667"
FT SITE 57
FT /note="Binds AChR"
FT /evidence="ECO:0000269|PubMed:21126549"
FT MOD_RES 63
FT /note="Cysteine amide"
FT /evidence="ECO:0000305|PubMed:16797781,
FT ECO:0000305|PubMed:21126549, ECO:0000305|PubMed:25617597"
FT DISULFID 52..60
FT /evidence="ECO:0000269|PubMed:21126549"
FT DISULFID 56..63
FT /evidence="ECO:0000269|PubMed:21126549"
FT MUTAGEN 57
FT /note="K->A: Exhibits higher activity as long-lasting
FT analgesic in the hotplate pain model in mice."
FT /evidence="ECO:0000269|PubMed:21126549"
FT CONFLICT 52
FT /note="C -> R (in Ref. 2; ABC74975)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 64 AA; 6878 MW; 3818FA217399D902 CRC64;
MKLSVMFIVF LMLTMPMTCA GISRSATNGG EADVRAHDKA ANLMALLQER MCPPLCKPSC
TNCG
