CSST1_CONNO
ID CSST1_CONNO Reviewed; 78 AA.
AC P0DW19;
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 Nc1 {ECO:0000303|PubMed:35319982};
DE Short=ConSST Nc1 {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 neocostatus (Cone snail) (Asprella neocostatus).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Conus.
OX NCBI_TaxID=2840447;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROBABLE GAMMA-CARBOXYGLUTAMATION AT GLU-61,
RP PROBABLE D-AMINO ACID AT TRP-64, AND PROBABLE HYDROXYLATION AT PRO-70.
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 Cleavage on pair of basic residues; D-amino acid; 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..59
FT /evidence="ECO:0000305|PubMed:35319982"
FT /id="PRO_0000456117"
FT PEPTIDE 60..70
FT /note="Consomatin Nc1"
FT /evidence="ECO:0000305|PubMed:35319982"
FT /id="PRO_0000456118"
FT PROPEP 71..78
FT /evidence="ECO:0000305|PubMed:35319982"
FT /id="PRO_0000456119"
FT MOD_RES 61
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000305|PubMed:35319982"
FT MOD_RES 64
FT /note="D-tryptophan"
FT /evidence="ECO:0000250|UniProtKB:P0DQT5,
FT ECO:0000305|PubMed:35319982"
FT MOD_RES 70
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:P0DQT5,
FT ECO:0000305|PubMed:35319982"
FT DISULFID 62..67
FT /evidence="ECO:0000250|UniProtKB:P0DQT5,
FT ECO:0000305|PubMed:35319982"
SQ SEQUENCE 78 AA; 9018 MW; 2DFC1F9610816B49 CRC64;
MQTAYWVMVM VMVWITAPLS EGGKPNDVIR GLVPDDLTPQ LILRSLISRR RSDKDVGKRM
ECYWKSCSRP LSRRHDLG