INS3B_CONGE
ID INS3B_CONGE Reviewed; 113 AA.
AC A0A0B5AC86;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 1.
DT 25-MAY-2022, entry version 23.
DE RecName: Full=Con-Ins G3b {ECO:0000303|PubMed:25605914};
DE AltName: Full=Insulin 3b {ECO:0000312|EMBL:AJD85822.1};
DE Contains:
DE RecName: Full=Con-Ins G3b B chain {ECO:0000303|PubMed:25605914};
DE Contains:
DE RecName: Full=Con-Ins G3b 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: It is noteworthy that in this dimer, in contrast to Con-Ins G1,
CC the chain B is amidated and not the chain A.
CC {ECO:0000250|UniProtKB:A0A0B5A8P4}.
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.
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DR EMBL; KP268618; AJD85822.1; -; mRNA.
DR AlphaFoldDB; A0A0B5AC86; -.
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 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 PROPEP 22..29
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_0000439313"
FT PEPTIDE 30..51
FT /note="Con-Ins G3b B chain"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_5002098282"
FT PROPEP 52..92
FT /note="C peptide"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_0000439314"
FT PEPTIDE 93..113
FT /note="Con-Ins G3b A chain"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_0000439315"
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 51
FT /note="Histidine amide"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5A8P4"
FT MOD_RES 96
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT MOD_RES 102
FT /note="4-hydroxyproline; partial"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT DISULFID 38..99
FT /note="Interchain (between B and A chains)"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT DISULFID 50..112
FT /note="Interchain (between B and A chains)"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT DISULFID 98..103
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
SQ SEQUENCE 113 AA; 12792 MW; 600FDBADEAFCBFE8 CRC64;
MTTSFYFLLV ALGLLLYVCQ SSFGNQHTRN SDTPKHRCGS ELADQYVQLC HGKRNDAGKK
RGRASPLWQR QGFLSMLKAK RNEAFFLQRD GRGIVEVCCD NPCTVATLMT FCH
