CA1_CONAH
ID CA1_CONAH Reviewed; 66 AA.
AC P0CH24;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 1.
DT 25-MAY-2022, entry version 22.
DE RecName: Full=Conopeptide-Ac1 {ECO:0000305};
DE AltName: Full=5P1 {ECO:0000303|PubMed:32111068};
DE AltName: Full=5P2 {ECO:0000303|PubMed:32111068};
DE AltName: Full=Conopeptide Ac3.1 {ECO:0000303|PubMed:20307606};
DE AltName: Full=Conotoxin-Ac1 {ECO:0000303|PubMed:32111068};
DE AltName: Full=Conotoxin-Ac1-O6P {ECO:0000303|PubMed:32111068};
DE Flags: Precursor; Fragment;
OS Conus achatinus (Little frog cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Pionoconus.
OX NCBI_TaxID=369967;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom duct;
RX PubMed=20307606; DOI=10.1016/j.peptides.2010.03.010;
RA Wu X.-C., Zhou M., Peng C., Shao X.-X., Guo Z.-Y., Chi C.-W.;
RT "Novel conopeptides in a form of disulfide-crosslinked dimer.";
RL Peptides 31:1001-1006(2010).
RN [2]
RP PROTEIN SEQUENCE OF 52-66, SYNTHESIS OF 52-66, FUNCTION, HYDROXYLATION AT
RP PRO-57 AND PRO-60, D-AMINO ACID AT TRP-64, MASS SPECTROMETRY, SUBCELLULAR
RP LOCATION, AND BIOASSAY.
RC TISSUE=Venom;
RX PubMed=32111068; DOI=10.3390/md18030135;
RA Liu X., Yao G., Wang K., Liu Y., Wan X., Jiang H.;
RT "Structural and functional characterization of conotoxins from Conus
RT achatinus targeting NMDAR.";
RL Mar. Drugs 18:0-0(2020).
CC -!- FUNCTION: Ac1 weakly inhibits N-methyl-D-aspartate receptor subunit 2B
CC (NR2B) (IC(50)=8.22 uM). In vivo, shortens sleep latency and extends
CC sleep time after lateral brain administration. Is more potent than Ac1-
CC O6P for these effects. Also has an analgesic activity similar to that
CC of Ac1-O6P. {ECO:0000269|PubMed:32111068}.
CC -!- FUNCTION: Ac1-O6P has no or very weak activity on voltage-gated
CC channels and receptors tested. In vivo, shortens sleep latency and
CC extends sleep time after lateral brain administration. Is less potent
CC than Ac1 for these effects. Also has an analgesic activity similar to
CC that of Ac1. {ECO:0000269|PubMed:32111068}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:32111068}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:32111068}.
CC -!- PTM: Ac1-O6P is hydroxylated once at Pro-60, whereas Ac1 is
CC hydroxylated at both Pro-57 and Pro-60. Trp-64 is supposed to be a D-
CC amino acid in Ac1-O6P. {ECO:0000269|PubMed:32111068}.
CC -!- PTM: Hydroxylation at Pro-57 is important for activity on N-methyl-D-
CC aspartate receptors, since Ac1 is 5-fold more potent than Ac1 on
CC NR2A/GRIN2A and NR2B/GRIN2B N-methyl-D-aspartate (NMDA) receptors.
CC {ECO:0000269|PubMed:32111068}.
CC -!- PTM: Synthetic peptides with carboxylated glutamate residues instead of
CC Glu-61 and Trp-65, with an optional amidation of Thr-66 show a higher
CC analgesic activity than morphine. {ECO:0000269|PubMed:32111068}.
CC -!- MASS SPECTROMETRY: Mass=1992.11; Method=MALDI; Note=Hydroxylated at
CC Pro-57 (Ac1).; Evidence={ECO:0000269|PubMed:32111068};
CC -!- MASS SPECTROMETRY: Mass=1976.11; Method=MALDI; Note=Not hydroxylated at
CC Pro-57 (Ac1-O6P).; Evidence={ECO:0000269|PubMed:32111068};
CC -!- MISCELLANEOUS: The mature peptide does not contain cysteine residue.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: Ac1 has no or very weak activity on voltage-gated sodium
CC channel, voltage-gated potassium channel, voltage-gated calcium
CC channels, and NR2A/GRIN2A N-methyl-D-aspartate (NMDA) receptors.
CC {ECO:0000269|PubMed:32111068}.
CC -!- MISCELLANEOUS: Ac1-O6P has no or very weak activity on voltage-gated
CC sodium channel, voltage-gated potassium channel, voltage-gated calcium
CC channels, NR2A/GRIN2A and NR2B/GRIN2B N-methyl-D-aspartate (NMDA)
CC receptors. {ECO:0000269|PubMed:32111068}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR AlphaFoldDB; P0CH24; -.
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: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 Cleavage on pair of basic residues; D-amino acid;
KW Direct protein sequencing; Hydroxylation; Ion channel impairing toxin;
KW Ionotropic glutamate receptor inhibitor; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL <1..17
FT /evidence="ECO:0000255"
FT PROPEP 18..51
FT /evidence="ECO:0000269|PubMed:32111068"
FT /id="PRO_0000397196"
FT PEPTIDE 52..66
FT /note="Conopeptide-Ac1"
FT /evidence="ECO:0000269|PubMed:32111068"
FT /id="PRO_0000397197"
FT MOD_RES 57
FT /note="Hydroxyproline; partial"
FT /evidence="ECO:0000269|PubMed:32111068"
FT MOD_RES 60
FT /note="Hydroxyproline"
FT /evidence="ECO:0000269|PubMed:32111068"
FT MOD_RES 64
FT /note="D-tryptophan; partial"
FT /evidence="ECO:0000305|PubMed:32111068"
FT NON_TER 1
SQ SEQUENCE 66 AA; 7860 MW; 8B30FF5CBC9B73F7 CRC64;
LGVLVTIFLV LFPMATLQLD GDQTADRHAG ERDQDPLEQY RNLKHVLRRT RNYYLYPARP
ENSWWT
