ID   CSST1_CONAE             Reviewed;          82 AA.
AC   P0DW23;
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 Ar1 {ECO:0000303|PubMed:35383850};
DE            Short=ConSST Ar1 {ECO:0000305};
DE   AltName: Full=Somatostatin-related peptide {ECO:0000303|PubMed:35383850};
DE            Short=SSRP {ECO:0000303|PubMed:35383850};
DE   Flags: Precursor;
OS   Conus arenatus (Sand-dusted cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus.
OX   NCBI_TaxID=89451;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom duct;
RX   PubMed=35383850; DOI=10.1093/molbev/msac075;
RA   Koch T.L., Ramiro I.B.L., Florez-Salcedo P., Engholm E., Jensen K.J.,
RA   Chase K., Olivera B.M., Bjoern-Yoshimoto W.E., Safavi-Hemami H.;
RT   "Reconstructing the origins of the somatostatin and allatostatin-C
RT   signaling systems using the accelerated evolution of biodiverse cone snail
RT   venoms.";
RL   Mol. Biol. Evol. 0:0-0(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:35383850}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:35383850}.
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:0000269|PubMed:35383850}.
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   D-amino acid; Disulfide bond; G-protein coupled receptor impairing toxin;
KW   Hydroxylation; Secreted; Signal; Toxin.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PROPEP          23..60
FT                   /evidence="ECO:0000305|PubMed:35383850"
FT                   /id="PRO_0000456128"
FT   PEPTIDE         61..73
FT                   /note="Consomatin Ar1"
FT                   /evidence="ECO:0000305|PubMed:35383850"
FT                   /id="PRO_0000456129"
FT   PROPEP          74..82
FT                   /evidence="ECO:0000305|PubMed:35383850"
FT                   /id="PRO_0000456130"
FT   MOD_RES         66
FT                   /note="D-tryptophan"
FT                   /evidence="ECO:0000250|UniProtKB:P0DQT5"
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         73
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000305"
FT   DISULFID        64..69
FT                   /evidence="ECO:0000250|UniProtKB:P0DQT5"
SQ   SEQUENCE   82 AA;  9491 MW;  BFCAE3AF21FC9DEB CRC64;
     MQTAYWVVVM MMMVWVTAPV SEGGKLSDVI WGLVPDDLTP QIILQILNAS RHAYRRVRPR
     GQICIWKVCP PLPQWIHPLV KR