ID   INS1_CONMR              Reviewed;         130 AA.
AC   A0A0B5A8Q6;
DT   15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-2015, sequence version 1.
DT   25-MAY-2022, entry version 26.
DE   RecName: Full=Con-Ins M1 {ECO:0000303|PubMed:25605914};
DE   AltName: Full=Insulin 1 {ECO:0000312|EMBL:AJD85835.1};
DE   Contains:
DE     RecName: Full=Con-Ins M1 B chain {ECO:0000303|PubMed:25605914};
DE   Contains:
DE     RecName: Full=Con-Ins M1 A chain {ECO:0000303|PubMed:25605914};
DE   Flags: Precursor;
OS   Conus marmoreus (Marble cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Conus.
OX   NCBI_TaxID=42752;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND AMIDATION AT SER-129.
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. Intraperitoneal injection of this peptide
CC       into zebrafish lowers blood glucose with the same potency than human
CC       insulin. In vivo, when applied to water, this peptide reduces overall
CC       locomotor activity of zebrafish larvae, observed as a significant
CC       decrease in the percentage of time spent swimming and movement
CC       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   -!- SIMILARITY: Belongs to the insulin family.
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DR   EMBL; KP268602; AJD85835.1; -; mRNA.
DR   AlphaFoldDB; A0A0B5A8Q6; -.
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   SMART; SM00078; IlGF; 1.
DR   SUPFAM; SSF56994; SSF56994; 1.
DR   PROSITE; PS00262; INSULIN; 1.
PE   1: Evidence at protein level;
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..21
FT                   /evidence="ECO:0000255"
FT   PEPTIDE         22..58
FT                   /note="Con-Ins M1 B chain"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5ABD9"
FT                   /id="PRO_5002112026"
FT   PROPEP          59..92
FT                   /note="C peptide"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5ABD9"
FT                   /id="PRO_0000439320"
FT   PEPTIDE         93..129
FT                   /note="Con-Ins M1 A chain"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5ABD9"
FT                   /id="PRO_0000439321"
FT   MOD_RES         34
FT                   /note="4-hydroxyproline; partial"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT   MOD_RES         118
FT                   /note="4-carboxyglutamate; partial"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT   MOD_RES         129
FT                   /note="Serine amide"
FT                   /evidence="ECO:0000305|PubMed:25605914"
FT   DISULFID        29..107
FT                   /evidence="ECO:0000305"
FT   DISULFID        41..110
FT                   /note="Interchain (between B and A chains)"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT   DISULFID        53..123
FT                   /note="Interchain (between B and A chains)"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT   DISULFID        109..114
FT                   /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
SQ   SEQUENCE   130 AA;  14223 MW;  D6CC778C70D5A1A7 CRC64;
     MTTSSYFLLV ALGLLLYVCQ SSFGGEHVCG SNQPNHPNGK CGSKMADYLE EQCEEEEAAH
     GGTNDARATT GRALSLSKRR GFLSMLKRRG KRNEASPLQR AGRGIVCECC KNHCTDEEFT
     EYCPHVTESG