ID   CSST3_CONMK             Reviewed;          70 AA.
AC   P0DW22;
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 Mrc3 {ECO:0000303|PubMed:35319982};
DE            Short=ConSST Mrc3 {ECO:0000305};
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], PROBABLE D-AMINO ACID AT TRP-64, PROBABLE
RP   HYDROXYLATION AT PRO-68, PROBABLE AMIDATION AT TYR-69, AND PROBABLE
RP   DISULFIDE BOND.
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   1: Evidence at protein level;
KW   Amidation; 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..55
FT                   /evidence="ECO:0000305|PubMed:35319982"
FT                   /id="PRO_0000456126"
FT   PEPTIDE         56..69
FT                   /note="Consomatin Mrc3"
FT                   /evidence="ECO:0000305|PubMed:35319982"
FT                   /id="PRO_0000456127"
FT   MOD_RES         64
FT                   /note="D-tryptophan"
FT                   /evidence="ECO:0000250|UniProtKB:P0DQT5,
FT                   ECO:0000305|PubMed:35319982"
FT   MOD_RES         68
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000305|PubMed:35319982"
FT   MOD_RES         69
FT                   /note="Tyrosine amide"
FT                   /evidence="ECO:0000305|PubMed:35319982"
FT   DISULFID        62..67
FT                   /evidence="ECO:0000250|UniProtKB:P0DQT5,
FT                   ECO:0000305|PubMed:35319982"
SQ   SEQUENCE   70 AA;  8017 MW;  C3DDCDCDCB2A6F16 CRC64;
     MQTAYWVMVM MMVWITAPLS EGGKLNDVIR GLVPDDVTPK RILQSLISRR RFDGRALFVP
     SCIWKTCPYG