ID   CSST1_CONMK             Reviewed;          80 AA.
AC   P0DW21;
DT   03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT   03-AUG-2022, sequence version 1.
DT   03-AUG-2022, entry version 1.
DE   RecName: Full=Consomatin Mrc1 {ECO:0000303|PubMed:35319982};
DE            Short=ConSST Mrc1 {ECO:0000303|PubMed:35319982};
DE   AltName: Full=Somatostatin-related peptide {ECO:0000250|UniProtKB:P0DQT5};
DE            Short=SSRP {ECO:0000250|UniProtKB:P0DQT5};
DE   Flags: Precursor;
OS   Conus mercator (Trader cone) (Varioconus mercator).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Varioconus.
OX   NCBI_TaxID=289040;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom duct;
RX   PubMed=35319982; DOI=10.1126/sciadv.abk1410;
RA   Ramiro I.B.L., Bjoern-Yoshimoto W.E., Imperial J.S., Gajewiak J.,
RA   Salcedo P.F., Watkins M., Taylor D., Resager W., Ueberheide B.,
RA   Braeuner-Osborne H., Whitby F.G., Hill C.P., Martin L.F., Patwardhan A.,
RA   Concepcion G.P., Olivera B.M., Safavi-Hemami H.;
RT   "Somatostatin venom analogs evolved by fish-hunting cone snails: from prey
RT   capture behavior to identifying drug leads.";
RL   Sci. Adv. 8:eabk1410-eabk1410(2022).
CC   -!- FUNCTION: Moderately activates human somatostatin receptors (SSTR) with
CC       a preferential activation of SSTR1 and SSTR4. In vivo, does not cause
CC       behavioral changes in mice within a few minutes of intracranial
CC       injection, but causes a progressive loss of movement thereafter. Four
CC       to five hours after injection, mice recover, even with the highest dose
CC       tested. Shows antinociception and antihyperalgesia activities in two
CC       mouse models of acute pain, most probably by acting outside the central
CC       nervous system. {ECO:0000250|UniProtKB:P0DQT5}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:35319982}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:35319982}.
CC   -!- DOMAIN: The cysteine framework is C-C. {ECO:0000305}.
CC   -!- MISCELLANEOUS: This peptide is an evolutionarily optimized stable
CC       analog of somatostatin. In addition, it adopts nearly identical
CC       conformations as in the somatostatin drug analog Octreotide. As this
CC       drug, it contains a D-Trp at the same position, whose synthesis is a
CC       common strategy used for enhancing the metabolic stability of compounds
CC       in drug design. {ECO:0000250|UniProtKB:P0DQT5}.
CC   -!- MISCELLANEOUS: Consomatins evolved by gene duplication of a
CC       'Somatostatin and related peptides (SSRP)' gene expressed in the snail
CC       neuroendocrine system. {ECO:0000250|UniProtKB:P0DQT5}.
CC   -!- MISCELLANEOUS: Does not activate any of the other 313 GPCRs tested.
CC       Shows little or no activating activity at the SSTR2, SSTR3 and SSTR5.
CC       {ECO:0000250|UniProtKB:P0DQT5}.
CC   -!- SIMILARITY: Belongs to the conotoxin C superfamily. Consomatin family.
CC       {ECO:0000305}.
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PE   3: Inferred from homology;
KW   Cleavage on pair of basic residues; D-amino acid; Disulfide bond;
KW   G-protein coupled receptor impairing toxin; Hydroxylation; Secreted;
KW   Signal; Toxin.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PROPEP          23..57
FT                   /evidence="ECO:0000305|PubMed:35319982"
FT                   /id="PRO_0000456123"
FT   PEPTIDE         58..73
FT                   /note="Consomatin Mrc1"
FT                   /evidence="ECO:0000305|PubMed:35319982"
FT                   /id="PRO_0000456124"
FT   PROPEP          74..80
FT                   /evidence="ECO:0000305|PubMed:35319982"
FT                   /id="PRO_0000456125"
FT   MOD_RES         65
FT                   /note="D-tryptophan"
FT                   /evidence="ECO:0000250|UniProtKB:P0DQT5, ECO:0000305"
FT   MOD_RES         69
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000305"
FT   MOD_RES         70
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000305"
FT   MOD_RES         71
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000305"
FT   MOD_RES         72
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000305"
FT   DISULFID        63..68
FT                   /evidence="ECO:0000250|UniProtKB:P0DQT5"
SQ   SEQUENCE   80 AA;  9105 MW;  8C3BC54A44D381D5 CRC64;
     MQTAYWVMVM MMVWITAPLS EGGKLNDVIR GLVPDDVTPQ LILRSLISRR PSDSVVRSTV
     HICYWKVCPP PPWRRPNGKG