ID   CONO1_CONML             Reviewed;           9 AA.
AC   P0DQM6;
DT   12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT   12-AUG-2020, sequence version 1.
DT   07-OCT-2020, entry version 2.
DE   RecName: Full=Conopressin-M1 {ECO:0000303|PubMed:32155768};
DE            Short=Con-M1 {ECO:0000303|PubMed:32155768};
OS   Conus miliaris (Thousand-spot cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Virroconus.
OX   NCBI_TaxID=97181;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SYNTHESIS, DISULFIDE BOND, AMIDATION
RP   AT SER-9, AND STRUCTURE BY NMR.
RX   PubMed=32155768; DOI=10.3390/md18030150;
RA   Giribaldi J., Ragnarsson L., Pujante T., Enjalbal C., Wilson D., Daly N.L.,
RA   Lewis R.J., Dutertre S.;
RT   "Synthesis, pharmacological and structural characterization of novel
RT   conopressins from Conus miliaris.";
RL   Mar. Drugs 18:0-0(2020).
CC   -!- FUNCTION: Shows reduced activity on vasopressin-oxytocin related
CC       receptors. Is more active on fish receptors, than on their human
CC       counterpart, supporting an evolved role of this conopressin in the
CC       envenomation process. Shows weak agonist activity on the zebrafish
CC       vasopressin receptor 1Ab (V1a1R) (EC(50)=13.6 uM). Also has weaker
CC       agonist activity on the human vasopressin receptor AVPR1B (EC(50)=38.2
CC       uM). Has no effect on all other receptors tested.
CC       {ECO:0000269|PubMed:32155768}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:32155768}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:32155768}.
CC   -!- DOMAIN: The cysteine framework is C-C. {ECO:0000305}.
CC   -!- DOMAIN: This synthetic peptide shows multiple conformations, possibly
CC       due to cis-trans isomerization. {ECO:0000269|PubMed:32155768}.
CC   -!- PTM: It is unsure whether Ser-9 is amidated or not, it is why the two
CC       forms have been synthesized. The non-amidated form shows a very weak
CC       agonist activity on the zebrafish vasopressin receptor 1Ab (V1a1R)
CC       (EC(50)=117 uM). The state of the C-terminal residue does not impact
CC       its 3D-structure. {ECO:0000269|PubMed:32155768}.
CC   -!- SIMILARITY: Belongs to the vasopressin/oxytocin family. {ECO:0000305}.
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DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   Amidation; Disulfide bond; G-protein coupled receptor impairing toxin;
KW   Secreted; Toxin.
FT   PEPTIDE         1..9
FT                   /note="Conopressin-M1"
FT                   /evidence="ECO:0000305|PubMed:32155768"
FT                   /id="PRO_0000450673"
FT   SITE            3
FT                   /note="Aromatic residue important for selectivity towards
FT                   vasopressin receptors"
FT                   /evidence="ECO:0000305|PubMed:32155768"
FT   SITE            8
FT                   /note="Non-basic residue surely responsible of very weak
FT                   activity"
FT                   /evidence="ECO:0000305|PubMed:32155768"
FT   MOD_RES         9
FT                   /note="Serine amide"
FT                   /evidence="ECO:0000305|PubMed:32155768"
FT   DISULFID        1..6
FT                   /evidence="ECO:0000305|PubMed:32155768"
SQ   SEQUENCE   9 AA;  939 MW;  C935B76EB4486769 CRC64;
     CFPGNCPDS