ID   CSST1_CONRO             Reviewed;          81 AA.
AC   P0DQT5;
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 Ro1 {ECO:0000303|PubMed:35319982, ECO:0000303|PubMed:35383850};
DE            Short=ConSST Ro1 {ECO:0000303|PubMed:35383850};
DE   AltName: Full=Somatostatin-related peptide {ECO:0000303|PubMed:35383850};
DE            Short=SSRP {ECO:0000303|PubMed:35383850};
DE   Flags: Precursor;
OS   Conus rolani (Cone snail).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Asprella.
OX   NCBI_TaxID=745791;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 58-70, FUNCTION, X-RAY
RP   CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 58-70, SUBCELLULAR LOCATION, MASS
RP   SPECTROMETRY, GAMMA-CARBOXYGLUTAMATION AT GLU-58, D-AMINO ACID AT TRP-64,
RP   HYDROXYLATION AT PRO-69, DISULFIDE BOND, BIOASSAY, SYNTHESIS OF 58-70, AND
RP   BIOTECHNOLOGY.
RC   TISSUE=Venom, and 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   [2]
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 (EC(50)=2.9 uM) and SSTR4
CC       (EC(50)=5.1 uM). In vivo, does not cause behavioral changes in mice
CC       within a few minutes of intracranial injection, but causes a
CC       progressive loss of movement thereafter. Four to five hours after
CC       injection, mice recover, even with the highest dose tested (5.4 mg/kg).
CC       Shows antinociception and antihyperalgesia activities in two mouse
CC       models of acute pain, most probably by acting outside the central
CC       nervous system. {ECO:0000269|PubMed:35319982}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:35319982}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:35319982}.
CC   -!- DOMAIN: The cysteine framework is C-C.
CC   -!- MASS SPECTROMETRY: Mass=1573.65; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:35319982};
CC   -!- BIOTECHNOLOGY: May represent a new lead for the potential development
CC       of an analgesic that acts via opioid-independent pathways.
CC       {ECO:0000305|PubMed:35319982}.
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:0000305|PubMed:35319982}.
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:0000269|PubMed:35319982}.
CC   -!- SIMILARITY: Belongs to the conotoxin C superfamily. Consomatin family.
CC       {ECO:0000305}.
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PE   1: Evidence at protein level;
KW   D-amino acid; Direct protein sequencing; Disulfide bond;
KW   G-protein coupled receptor impairing toxin; Gamma-carboxyglutamic acid;
KW   Hydroxylation; Secreted; Signal; Toxin.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PROPEP          23..57
FT                   /evidence="ECO:0000305|PubMed:35383850"
FT                   /id="PRO_0000456104"
FT   PEPTIDE         58..70
FT                   /note="Consomatin Ro1"
FT                   /evidence="ECO:0000269|PubMed:35383850"
FT                   /id="PRO_0000456105"
FT   PROPEP          71..81
FT                   /evidence="ECO:0000305|PubMed:35383850"
FT                   /id="PRO_0000456106"
FT   MOD_RES         58
FT                   /note="4-carboxyglutamate"
FT                   /evidence="ECO:0000269|PubMed:35383850"
FT   MOD_RES         64
FT                   /note="D-tryptophan"
FT                   /evidence="ECO:0000269|PubMed:35383850"
FT   MOD_RES         69
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000269|PubMed:35383850"
FT   DISULFID        62..67
FT                   /evidence="ECO:0000269|PubMed:35383850"
SQ   SEQUENCE   81 AA;  9461 MW;  85B1F87F71960599 CRC64;
     MQTAYWVMVM MMVWITAPLS EGGKPNDVIR GLVPDDLTPQ LILRSLISRR RSDKDVREGY
     KCVWKTCMPA LWRRHDLKGK D