INS1C_CONGE
ID INS1C_CONGE Reviewed; 115 AA.
AC A0A0B5A7P2;
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 G1c {ECO:0000303|PubMed:25605914};
DE AltName: Full=Insulin 1c {ECO:0000312|EMBL:AJD85839.1};
DE Contains:
DE RecName: Full=Con-Ins G1 B chain {ECO:0000303|PubMed:25605914};
DE Contains:
DE RecName: Full=Con-Ins G1c 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. It is
CC one of the smallest known insulin found in nature and lacks the C-
CC terminal segment of the B chain that, in human insulin, mediates
CC engagement of the insulin receptor and assembly of the hormone's
CC hexameric storage form. Despite lacking this segment, it both binds and
CC activates human insulin receptor (long isoform (HIR-B)) with only a 10-
CC fold lower potency. In vivo, intraperitoneal injection of this peptide
CC into zebrafish lowers blood glucose with the same potency than human
CC insulin. In addition, when applied to water, this peptide reduces
CC overall locomotor activity of zebrafish larvae, observed as a
CC significant decrease in the percentage of time spent swimming and
CC movement frequency. {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 -!- PTM: Is different from Con-Ins G1a (AC A0A0B5AC95) due to absence of
CC amidation at Cys-114. {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. {ECO:0000305}.
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DR EMBL; KP268609; AJD85839.1; -; mRNA.
DR AlphaFoldDB; A0A0B5A7P2; -.
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; IPR022353; Insulin_CS.
DR InterPro; IPR022352; Insulin_family.
DR Pfam; PF00049; Insulin; 1.
DR PRINTS; PR00276; INSULINFAMLY.
DR SMART; SM00078; IlGF; 1.
DR SUPFAM; SSF56994; SSF56994; 1.
DR PROSITE; PS00262; INSULIN; 1.
PE 3: Inferred from homology;
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..24
FT /evidence="ECO:0000255"
FT PROPEP 25..29
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_0000439297"
FT PEPTIDE 30..52
FT /note="Con-Ins G1 B chain"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_5002097947"
FT PROPEP 53..94
FT /note="C peptide"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_0000439298"
FT PEPTIDE 95..115
FT /note="Con-Ins G1c A chain"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_0000439299"
FT MOD_RES 34
FT /note="4-hydroxyproline; partial"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT MOD_RES 41
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT MOD_RES 98
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT MOD_RES 104
FT /note="4-hydroxyproline; partial"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT MOD_RES 109
FT /note="4-carboxyglutamate; partial"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT DISULFID 38..101
FT /note="Interchain (between B and A chains)"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT DISULFID 50..114
FT /note="Interchain (between B and A chains)"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT DISULFID 100..105
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
SQ SEQUENCE 115 AA; 13223 MW; 1A45BB7425B71A26 CRC64;
MTTSFYFLLM ALGLLLYVCQ SSFGNQHTRT FDTPKHRCGS EITNSYMDLC YRKRNDAGKK
RGRASPLWQR RGSLSQLKAR AKRNGAFHLP RDGRGVVEHC CHRPCSNAEF KKYCS
