ID   INS2B_CONGE             Reviewed;         130 AA.
AC   A0A0B5ADT3;
DT   15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-2015, sequence version 1.
DT   25-MAY-2022, entry version 24.
DE   RecName: Full=Con-Ins G2b {ECO:0000303|PubMed:25605914};
DE   AltName: Full=Insulin 2b {ECO:0000312|EMBL:AJD85823.1};
DE   Contains:
DE     RecName: Full=Con-Ins G2b B chain {ECO:0000303|PubMed:25605914};
DE   Contains:
DE     RecName: Full=Con-Ins G2b A chain {ECO:0000303|PubMed:25605914};
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]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=25605914; DOI=10.1073/pnas.1423857112;
RA   Safavi-Hemami H., Gajewiak J., Karanth S., Robinson S.D., Ueberheide B.,
RA   Douglass A.D., Schlegel A., Imperial J.S., Watkins M., Bandyopadhyay P.K.,
RA   Yandell M., Li Q., Purcell A.W., Norton R.S., Ellgaard L., Olivera B.M.;
RT   "Specialized insulin is used for chemical warfare by fish-hunting cone
RT   snails.";
RL   Proc. Natl. Acad. Sci. U.S.A. 112:1743-1748(2015).
CC   -!- FUNCTION: This venom insulin, from a fish-hunting cone snail,
CC       facilitates prey capture by rapidly inducing hypoglycemic shock.
CC       Intraperitoneal injection of this peptide into zebrafish lowers blood
CC       glucose with the same potency than human insulin. In vivo, when applied
CC       to water, this peptide reduces overall locomotor activity of zebrafish
CC       larvae, observed as a significant decrease in the percentage of time
CC       spent swimming and movement frequency.
CC       {ECO:0000250|UniProtKB:A0A0B5AC95}.
CC   -!- SUBUNIT: Heterodimer of A and B chains; disulfide-linked.
CC       {ECO:0000250|UniProtKB:A0A0B5AC95}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:A0A0B5AC95}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:25605914}.
CC   -!- MISCELLANEOUS: Venom insulins constitute about 1/25 of the total venom
CC       of C.geographus. {ECO:0000305|PubMed:25605914}.
CC   -!- SIMILARITY: Belongs to the insulin family.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; KP268614; AJD85823.1; -; mRNA.
DR   AlphaFoldDB; A0A0B5ADT3; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR   InterPro; IPR016179; Insulin-like.
DR   InterPro; IPR036438; Insulin-like_sf.
DR   InterPro; IPR016724; Insulin-rel_pep.
DR   InterPro; IPR022353; Insulin_CS.
DR   Pfam; PF00049; Insulin; 1.
DR   PIRSF; PIRSF018431; Molluscan_insulin_rel_peptide; 1.
DR   SUPFAM; SSF56994; SSF56994; 1.
DR   PROSITE; PS00262; INSULIN; 1.
PE   2: Evidence at transcript level;
KW   Carbohydrate metabolism; Cleavage on pair of basic residues;
KW   Disulfide bond; Gamma-carboxyglutamic acid; Glucose metabolism; Hormone;
KW   Hydroxylation; Secreted; Signal; Toxin.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   PEPTIDE         24..58
FT                   /note="Con-Ins G2b B chain"
FT                   /id="PRO_5002098014"
FT   PROPEP          59..92
FT                   /note="C peptide"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5ABD9"
FT                   /id="PRO_0000439318"
FT   PEPTIDE         94..130
FT                   /note="Con-Ins G2b A chain"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5ABD9"
FT                   /id="PRO_0000439319"
FT   REGION          54..77
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        54..70
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         34
FT                   /note="4-hydroxyproline; partial"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT   MOD_RES         111
FT                   /note="4-carboxyglutamate; partial"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT   DISULFID        29..100
FT                   /evidence="ECO:0000305"
FT   DISULFID        41..103
FT                   /note="Interchain (between B and A chains)"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT   DISULFID        53..116
FT                   /note="Interchain (between B and A chains)"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT   DISULFID        102..107
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
SQ   SEQUENCE   130 AA;  14726 MW;  80A541D57FB25846 CRC64;
     MTTSSYFLLV ALGLLLYVRQ SFSTHEHTCQ LDDPAHPQGK CGSDLVNYHE EKCEEEEARR
     GGTNDGGKKR RRASPLRKRR RFISMLKARA KRRGYQGIAC ECCQHYCTDQ EFINYCPPVT
     ESSSSSSSAV