INS1A_CONTU
ID INS1A_CONTU Reviewed; 115 AA.
AC A0A0B5ADU4;
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 T1A {ECO:0000303|PubMed:30747102};
DE AltName: Full=Con-Ins T1 {ECO:0000303|PubMed:25605914};
DE AltName: Full=Insulin 1 {ECO:0000312|EMBL:AJD85833.1};
DE Contains:
DE RecName: Full=Con-Ins T1A B chain {ECO:0000303|PubMed:30747102};
DE AltName: Full=Con-Ins T1 B chain {ECO:0000303|PubMed:25605914};
DE Contains:
DE RecName: Full=Con-Ins T1A A chain {ECO:0000303|PubMed:30747102};
DE AltName: Full=Con-Ins T1 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).
RN [2]
RP FUNCTION, SYNTHESIS OF 30-52 AND 95-114, AND 3D-STRUCTURE MODELING IN
RP COMPLEX WITH HUMAN INSULIN RECEPTOR.
RX PubMed=30747102; DOI=10.7554/elife.41574;
RA Ahorukomeye P., Disotuar M.M., Gajewiak J., Karanth S., Watkins M.,
RA Robinson S.D., Florez Salcedo P., Smith N.A., Smith B.J., Schlegel A.,
RA Forbes B.E., Olivera B., Hung-Chieh Chou D., Safavi-Hemami H.;
RT "Fish-hunting cone snail venoms are a rich source of minimized ligands of
RT the vertebrate insulin receptor.";
RL Elife 8:0-0(2019).
CC -!- FUNCTION: This venom insulin, from a fish-hunting cone snail,
CC facilitates prey capture by rapidly inducing hypoglycemic shock
CC (PubMed:30747102). It is one of the smallest known insulin found in
CC nature and lacks the C-terminal segment of the B chain that, in human
CC insulin, mediates engagement of the insulin receptor and assembly of
CC the hormone's hexameric storage form (By similarity). Despite lacking
CC this segment, it both binds and activates human insulin receptor (long
CC isoform (HIR-B)) with a high potency (EC(50)=12.0 nM)
CC (PubMed:30747102). In vivo, intraperitoneal injection of this peptide
CC into zebrafish lowers blood glucose with a lower potency than human
CC insulin (PubMed:30747102). In addition, when applied to water, this
CC peptide reduces overall locomotor activity of zebrafish larvae,
CC observed as a significant decrease in the percentage of time spent
CC swimming and movement frequency (By similarity). When tested on a mouse
CC model of diabetes, this insulin also lowers blood glucose with a 10-
CC fold lower potency than human insulin (PubMed:30747102).
CC {ECO:0000250|UniProtKB:A0A0B5AC95, ECO:0000269|PubMed:30747102}.
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: Is possibly an allelic variant of Con-Ins T1B (AC
CC A0A0B5AC90). {ECO:0000305|PubMed:30747102}.
CC -!- SIMILARITY: Belongs to the insulin family.
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DR EMBL; KP268600; AJD85833.1; -; mRNA.
DR AlphaFoldDB; A0A0B5ADU4; -.
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_0000439300"
FT PEPTIDE 30..52
FT /note="Con-Ins T1A B chain"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_5002098295"
FT PROPEP 53..94
FT /note="C peptide"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_0000439301"
FT PEPTIDE 95..114
FT /note="Con-Ins T1A A chain"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC95"
FT /id="PRO_0000439302"
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"
SQ SEQUENCE 115 AA; 13161 MW; F4E9A328A68FA8D9 CRC64;
MTTSFYFLLM ALGLLLYVCQ SSFGNQHTRN SDTPKYRCGS EIPNSYIDLC FRKRNDAGKK
RGRASPLWQR GGSLSMLKAR AKRNEAFHLQ RAHRGVVEHC CHRPCSNAEF KKFCG
