INS1B_CONGE
ID INS1B_CONGE Reviewed; 115 AA.
AC A0A0B5A8Q2;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 1.
DT 25-MAY-2022, entry version 29.
DE RecName: Full=Con-Ins G1b {ECO:0000303|PubMed:25605914};
DE AltName: Full=Insulin 1b {ECO:0000312|EMBL:AJD85830.1};
DE Contains:
DE RecName: Full=Con-Ins G1 B chain {ECO:0000303|PubMed:25605914};
DE Contains:
DE RecName: Full=Con-Ins G1b 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).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 30-52, AND SYNTHESIS OF 30-52.
RX PubMed=27617429; DOI=10.1038/nsmb.3292;
RA Menting J.G., Gajewiak J., MacRaild C.A., Chou D.H., Disotuar M.M.,
RA Smith N.A., Miller C., Erchegyi J., Rivier J.E., Olivera B.M., Forbes B.E.,
RA Smith B.J., Norton R.S., Safavi-Hemami H., Lawrence M.C.;
RT "A minimized human insulin-receptor-binding motif revealed in a Conus
RT geographus venom insulin.";
RL Nat. Struct. Mol. Biol. 23:916-920(2016).
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 -!- 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; KP268607; AJD85830.1; -; mRNA.
DR PDB; 5JYQ; X-ray; 1.95 A; B=30-52.
DR PDB; 6VEQ; X-ray; 3.25 A; B/H=30-52.
DR PDBsum; 5JYQ; -.
DR PDBsum; 6VEQ; -.
DR AlphaFoldDB; A0A0B5A8Q2; -.
DR SMR; A0A0B5A8Q2; -.
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 1: Evidence at protein level;
KW 3D-structure; Amidation; Carbohydrate metabolism;
KW Cleavage on pair of basic residues; Disulfide bond;
KW Gamma-carboxyglutamic acid; Glucose metabolism; Hormone; Hydroxylation;
KW Secreted; Signal; Toxin.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..29
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_0000439294"
FT PEPTIDE 30..51
FT /note="Con-Ins G1 B chain"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_5002097968"
FT PROPEP 52..94
FT /note="C peptide"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_0000439295"
FT PEPTIDE 95..114
FT /note="Con-Ins G1b A chain"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_0000439296"
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 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"
FT HELIX 40..49
FT /evidence="ECO:0007829|PDB:5JYQ"
SQ SEQUENCE 115 AA; 13282 MW; F578787A3C961A32 CRC64;
MTTSFYFLLM ALGLLLYVCQ SSFGNQHTRT FDTPKHRCGS EITNSYMDLC YRKRNDAGEK
RGRASPLWQR RGFLSKLKAR AKRNGAFHLP RDGRGVVEHC CHRPCSNAEF RKYCG
