ID   CLE1A_CONCL             Reviewed;          66 AA.
AC   P0DUQ5;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   29-SEP-2021, sequence version 1.
DT   23-FEB-2022, entry version 2.
DE   RecName: Full=Conotoxin Cl14.1a {ECO:0000303|PubMed:20363338};
DE   AltName: Full=Conotoxin Cal14.1a {ECO:0000303|PubMed:27070627};
DE   Flags: Precursor;
OS   Californiconus californicus (California cone) (Conus californicus).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Californiconus.
OX   NCBI_TaxID=1736779;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=20363338; DOI=10.1016/j.ympev.2010.03.029;
RA   Biggs J.S., Watkins M., Puillandre N., Ownby J.P., Lopez-Vera E.,
RA   Christensen S., Moreno K.J., Bernaldez J., Licea-Navarro A., Corneli P.S.,
RA   Olivera B.M.;
RT   "Evolution of Conus peptide toxins: analysis of Conus californicus Reeve,
RT   1844.";
RL   Mol. Phylogenet. Evol. 56:1-12(2010).
RN   [2]
RP   FUNCTION, AND SYNTHESIS OF 50-66.
RX   PubMed=27070627; DOI=10.3390/md14040066;
RA   De Leon-Nava M.A., Romero-Nunez E., Luna-Nophal A., Bernaldez-Sarabia J.,
RA   Sanchez-Campos L.N., Licea-Navarro A.F., Morales-Montor J.,
RA   Muniz-Hernandez S.;
RT   "In vitro effect of the synthetic cal14.1a conotoxin, derived from Conus
RT   californicus, on the human parasite Toxoplasma gondii.";
RL   Mar. Drugs 14:0-0(2016).
RN   [3]
RP   FUNCTION, AND SYNTHESIS OF 50-66.
RX   PubMed=26861394; DOI=10.3390/toxins8020038;
RA   Oroz-Parra I., Navarro M., Cervantes-Luevano K.E., Alvarez-Delgado C.,
RA   Salvesen G., Sanchez-Campos L.N., Licea-Navarro A.F.;
RT   "Apoptosis Activation in Human Lung Cancer Cell Lines by a Novel Synthetic
RT   Peptide Derived from Conus californicus Venom.";
RL   Toxins 8:38-38(2016).
RN   [4]
RP   FUNCTION, AND SYNTHESIS OF 50-66.
RX   PubMed=33061442; DOI=10.2147/ott.s264600;
RA   Jiang H., Li L., Zhang J., Wan Z., Wang Y., Hou J., Yu Y.;
RT   "MiR-101-3p and Syn-Cal14.1a synergy in suppressing EZH2-induced
RT   progression of breast cancer.";
RL   Onco Targets Ther. 13:9599-9609(2020).
CC   -!- FUNCTION: Probable neurotoxin with unknown target (Probable). Possibly
CC       targets ion channels (Probable). This peptide could be considered as a
CC       potential apoptosis activator in some cancers (tested on lung and
CC       breast cancer cell lines) (Probable). When treated with this synthetic
CC       peptide, lung cancer cell lines have decreased cell viability,
CC       activated caspases, and reduced expression of the pro-survival protein
CC       NF-kappa-B (NFKB1) (PubMed:26861394). In synergy with MicroRNA-101-3p,
CC       this synthetic peptide inhibits breast cancer cells through suppressing
CC       the expression of the methyltransferase EZH2 (PubMed:33061442). Against
CC       microbes, this synthetic toxin (at micromolar concentrations) lowers
CC       viability and inhibits host cell invasion by the opportunistic parasite
CC       Toxoplasma gondii (tachyzoite form) (PubMed:27070627). In addition, it
CC       permits T.gondii intracellular replication to decrease while viability
CC       of the host cell is unaffected (PubMed:27070627).
CC       {ECO:0000269|PubMed:26861394, ECO:0000269|PubMed:27070627,
CC       ECO:0000269|PubMed:33061442, ECO:0000305, ECO:0000305|PubMed:26861394,
CC       ECO:0000305|PubMed:33061442}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:26861394,
CC       ECO:0000305|PubMed:27070627}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:26861394, ECO:0000305|PubMed:27070627}.
CC   -!- DOMAIN: The cysteine framework is XIV (C-C-C-C). {ECO:0000305}.
CC   -!- PTM: Contains 2 disulfide bonds. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the conotoxin L superfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=ADB93099.1; Type=Miscellaneous discrepancy; Note=Submitted sequence does not correspond to the one indicated in the paper. It may have been erroneously substituted by that of conotoxin Cl14.2c.; Evidence={ECO:0000305|PubMed:20363338};
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DR   EMBL; FJ959129; ADB93099.1; ALT_SEQ; Genomic_DNA.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE   3: Inferred from homology;
KW   Antimicrobial; Cleavage on pair of basic residues; Disulfide bond;
KW   Ion channel impairing toxin; Neurotoxin; Secreted; Signal; Toxin.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   PROPEP          20..49
FT                   /evidence="ECO:0000305|PubMed:20363338"
FT                   /id="PRO_0000453211"
FT   PEPTIDE         50..66
FT                   /note="Conotoxin Cl14.1a"
FT                   /evidence="ECO:0000305|PubMed:20363338"
FT                   /id="PRO_0000453212"
FT   UNSURE          20..49
FT                   /note="Assigned by comparison with orthologs"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   66 AA;  7273 MW;  F2C98E4A6BE93E42 CRC64;
     MNVTAMFIVL LLTMPLTDGF NIRAINGGEL FGLVQRDAGN ALDHGFYRRG DCPPWCVGAR
     CRAEKC