ID   CSST2_CONGE             Reviewed;          93 AA.
AC   X5IXY8;
DT   03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT   11-JUN-2014, sequence version 1.
DT   03-AUG-2022, entry version 9.
DE   RecName: Full=Consomatin G2 {ECO:0000303|PubMed:35319982};
DE            Short=ConSST G2 {ECO:0000305};
DE   AltName: Full=Somatostatin-related peptide {ECO:0000303|PubMed:35383850};
DE            Short=SSRP {ECO:0000303|PubMed:35383850};
DE   Flags: Precursor;
OS   Conus geographus (Geography cone) (Nubecula geographus).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Gastridium.
OX   NCBI_TaxID=6491;
RN   [1] {ECO:0000312|EMBL:BAO65575.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom duct;
RX   PubMed=24662800; DOI=10.1038/ncomms4521;
RA   Dutertre S., Jin A.-H., Vetter I., Hamilton B., Sunagar K., Lavergne V.,
RA   Dutertre V., Fry B.G., Antunes A., Venter D.J., Alewood P.F., Lewis R.J.;
RT   "Evolution of separate predation- and defence-evoked venoms in carnivorous
RT   cone snails.";
RL   Nat. Commun. 5:3521-3521(2014).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROBABLE D-AMINO ACID AT TRP-74, 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).
RN   [3]
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:24662800}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:24662800}.
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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DR   EMBL; AB910807; BAO65575.1; -; mRNA.
PE   1: Evidence at protein level;
KW   D-amino acid; Disulfide bond; G-protein coupled receptor impairing toxin;
KW   Secreted; Signal; Toxin.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   PROPEP          19..69
FT                   /evidence="ECO:0000305|PubMed:35319982,
FT                   ECO:0000305|PubMed:35383850"
FT                   /id="PRO_0000456115"
FT   PEPTIDE         70..78
FT                   /note="Consomatin G2"
FT                   /id="PRO_5004956872"
FT   PROPEP          79..93
FT                   /evidence="ECO:0000305|PubMed:35319982,
FT                   ECO:0000305|PubMed:35383850"
FT                   /id="PRO_0000456116"
FT   MOD_RES         74
FT                   /note="D-tryptophan"
FT                   /evidence="ECO:0000250|UniProtKB:P0DQT5,
FT                   ECO:0000305|PubMed:35319982"
FT   DISULFID        72..77
FT                   /evidence="ECO:0000250|UniProtKB:P0DQT5,
FT                   ECO:0000305|PubMed:35319982"
SQ   SEQUENCE   93 AA;  10802 MW;  8631984238052423 CRC64;
     MQTAYWVMLM MMVCITAPLP EGGKPNSGIR GLVPNDLTPQ HTLRSLISRR QTDVLLDATL
     LTTPAPEQRL FCFWKSCTWR PYPWRRRDLN GKR