ID   INS3_CONTU              Reviewed;         117 AA.
AC   A0A0B5ABD5;
DT   15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-2015, sequence version 1.
DT   25-MAY-2022, entry version 22.
DE   RecName: Full=Con-Ins T3 {ECO:0000303|PubMed:25605914};
DE   AltName: Full=Insulin 3 {ECO:0000312|EMBL:AJD85821.1};
DE   Contains:
DE     RecName: Full=Con-Ins T3 B chain {ECO:0000303|PubMed:25605914};
DE   Contains:
DE     RecName: Full=Con-Ins T3 A chain {ECO:0000303|PubMed:25605914};
DE   Flags: Precursor;
OS   Conus tulipa (Fish-hunting cone snail) (Tulip cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Gastridium.
OX   NCBI_TaxID=6495;
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 facilitates prey capture by rapidly
CC       inducing hypoglycemic shock. It is one of the smallest known insulin
CC       found in nature and lacks the C-terminal segment of the B chain that,
CC       in human insulin, mediates engagement of the insulin receptor and
CC       assembly of the hormone's hexameric storage form. Despite lacking this
CC       segment, it both binds and activates human insulin receptor (long
CC       isoform (HIR-B)) with only a 10-fold lower potency. In vivo,
CC       intraperitoneal injection of this peptide into zebrafish lowers blood
CC       glucose with the same potency than human insulin. In addition, when
CC       applied to water, this peptide reduces overall locomotor activity of
CC       zebrafish larvae, observed as a significant decrease in the percentage
CC       of time 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   -!- SIMILARITY: Belongs to the insulin family.
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DR   EMBL; KP268617; AJD85821.1; -; mRNA.
DR   AlphaFoldDB; A0A0B5ABD5; -.
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   Pfam; PF00049; Insulin; 1.
DR   SMART; SM00078; IlGF; 1.
DR   SUPFAM; SSF56994; SSF56994; 1.
DR   PROSITE; PS00262; INSULIN; 1.
PE   3: Inferred from homology;
KW   Amidation; 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_0000439306"
FT   PEPTIDE         30..52
FT                   /note="Con-Ins T3 B chain"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT                   /id="PRO_5002097994"
FT   PROPEP          53..94
FT                   /note="C peptide"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT                   /id="PRO_0000439307"
FT   PEPTIDE         95..114
FT                   /note="Con-Ins T3 A chain"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT                   /id="PRO_0000439308"
FT   PROPEP          116..117
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000439309"
FT   MOD_RES         34
FT                   /note="4-hydroxyproline; partial"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT   MOD_RES         98
FT                   /note="4-carboxyglutamate"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT   MOD_RES         109
FT                   /note="4-carboxyglutamate; partial"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT   MOD_RES         114
FT                   /note="Cysteine amide"
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   117 AA;  13306 MW;  A5AA86FDA26C17A0 CRC64;
     MTTSFYFLLM ALGLLLYVCQ SSFGNQHTRN SDTPKYRCGS DIPNSYMDLC FRKRNDAGKK
     RGQASPLWQR GGSLSMLKAR AKRNEAFHLQ RAHRGVVEHC CKRACSNAEF MQFCGNS