ID   INS_CANLF               Reviewed;         110 AA.
AC   P01321;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   03-AUG-2022, entry version 139.
DE   RecName: Full=Insulin;
DE   Contains:
DE     RecName: Full=Insulin B chain;
DE   Contains:
DE     RecName: Full=Insulin A chain;
DE   Flags: Precursor;
GN   Name=INS;
OS   Canis lupus familiaris (Dog) (Canis familiaris).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX   NCBI_TaxID=9615;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6296142; DOI=10.1016/s0021-9258(18)32931-4;
RA   Kwok S.C.M., Chan S.J., Steiner D.F.;
RT   "Cloning and nucleotide sequence analysis of the dog insulin gene. Coded
RT   amino acid sequence of canine preproinsulin predicts an additional C-
RT   peptide fragment.";
RL   J. Biol. Chem. 258:2357-2363(1983).
RN   [2]
RP   PROTEIN SEQUENCE OF 25-54 AND 90-110.
RX   PubMed=5949593; DOI=10.1016/0002-9343(66)90145-8;
RA   Smith L.F.;
RT   "Species variation in the amino acid sequence of insulin.";
RL   Am. J. Med. 40:662-666(1966).
CC   -!- FUNCTION: Insulin decreases blood glucose concentration. It increases
CC       cell permeability to monosaccharides, amino acids and fatty acids. It
CC       accelerates glycolysis, the pentose phosphate cycle, and glycogen
CC       synthesis in liver.
CC   -!- SUBUNIT: Heterodimer of a B chain and an A chain linked by two
CC       disulfide bonds. {ECO:0000250|UniProtKB:P01308}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SIMILARITY: Belongs to the insulin family. {ECO:0000305}.
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DR   EMBL; V00179; CAA23475.1; -; Genomic_DNA.
DR   PIR; A92413; IPDG.
DR   RefSeq; NP_001123565.1; NM_001130093.1.
DR   AlphaFoldDB; P01321; -.
DR   BMRB; P01321; -.
DR   SMR; P01321; -.
DR   STRING; 9615.ENSCAFP00000051648; -.
DR   PaxDb; P01321; -.
DR   Ensembl; ENSCAFT00845019762; ENSCAFP00845015468; ENSCAFG00845011141.
DR   GeneID; 483665; -.
DR   KEGG; cfa:483665; -.
DR   CTD; 3630; -.
DR   VEuPathDB; HostDB:ENSCAFG00845011141; -.
DR   eggNOG; ENOG502T8I0; Eukaryota.
DR   GeneTree; ENSGT00390000015440; -.
DR   HOGENOM; CLU_140421_1_0_1; -.
DR   InParanoid; P01321; -.
DR   OMA; LANQHLC; -.
DR   OrthoDB; 1644517at2759; -.
DR   Reactome; R-CFA-264876; Insulin processing.
DR   Reactome; R-CFA-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR   Reactome; R-CFA-6807878; COPI-mediated anterograde transport.
DR   Reactome; R-CFA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-CFA-74713; IRS activation.
DR   Reactome; R-CFA-74749; Signal attenuation.
DR   Reactome; R-CFA-74751; Insulin receptor signalling cascade.
DR   Reactome; R-CFA-74752; Signaling by Insulin receptor.
DR   Reactome; R-CFA-77387; Insulin receptor recycling.
DR   Proteomes; UP000002254; Chromosome 18.
DR   Bgee; ENSCAFG00000010092; Expressed in pancreas and 7 other tissues.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0005158; F:insulin receptor binding; IEA:Ensembl.
DR   GO; GO:0005159; F:insulin-like growth factor receptor binding; IEA:Ensembl.
DR   GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR   GO; GO:0032148; P:activation of protein kinase B activity; IEA:Ensembl.
DR   GO; GO:0006953; P:acute-phase response; IEA:Ensembl.
DR   GO; GO:0046631; P:alpha-beta T cell activation; IEA:Ensembl.
DR   GO; GO:0055089; P:fatty acid homeostasis; IEA:Ensembl.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0042593; P:glucose homeostasis; IBA:GO_Central.
DR   GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0008286; P:insulin receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0002674; P:negative regulation of acute inflammatory response; IEA:Ensembl.
DR   GO; GO:0045922; P:negative regulation of fatty acid metabolic process; IEA:Ensembl.
DR   GO; GO:2000252; P:negative regulation of feeding behavior; IEA:Ensembl.
DR   GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR   GO; GO:0045818; P:negative regulation of glycogen catabolic process; IEA:Ensembl.
DR   GO; GO:0050995; P:negative regulation of lipid catabolic process; IEA:Ensembl.
DR   GO; GO:0033861; P:negative regulation of NAD(P)H oxidase activity; IEA:Ensembl.
DR   GO; GO:0042177; P:negative regulation of protein catabolic process; IEA:Ensembl.
DR   GO; GO:0050709; P:negative regulation of protein secretion; IEA:Ensembl.
DR   GO; GO:0045861; P:negative regulation of proteolysis; IEA:Ensembl.
DR   GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IEA:Ensembl.
DR   GO; GO:0060266; P:negative regulation of respiratory burst involved in inflammatory response; IEA:Ensembl.
DR   GO; GO:1990535; P:neuron projection maintenance; IEA:Ensembl.
DR   GO; GO:0038060; P:nitric oxide-cGMP-mediated signaling pathway; IEA:Ensembl.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR   GO; GO:0001819; P:positive regulation of cytokine production; IEA:Ensembl.
DR   GO; GO:1902952; P:positive regulation of dendritic spine maintenance; IEA:Ensembl.
DR   GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl.
DR   GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; IEA:Ensembl.
DR   GO; GO:0045821; P:positive regulation of glycolytic process; IEA:Ensembl.
DR   GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR   GO; GO:0045840; P:positive regulation of mitotic nuclear division; IEA:Ensembl.
DR   GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IEA:Ensembl.
DR   GO; GO:0010750; P:positive regulation of nitric oxide mediated signal transduction; IEA:Ensembl.
DR   GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR   GO; GO:0051897; P:positive regulation of protein kinase B signaling; IEA:Ensembl.
DR   GO; GO:1900182; P:positive regulation of protein localization to nucleus; IEA:Ensembl.
DR   GO; GO:0050714; P:positive regulation of protein secretion; IBA:GO_Central.
DR   GO; GO:0060267; P:positive regulation of respiratory burst; IEA:Ensembl.
DR   GO; GO:0006521; P:regulation of cellular amino acid metabolic process; IEA:Ensembl.
DR   GO; GO:1903076; P:regulation of protein localization to plasma membrane; IEA:Ensembl.
DR   GO; GO:0022898; P:regulation of transmembrane transporter activity; IEA:Ensembl.
DR   GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR   GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR   CDD; cd04367; IlGF_insulin_like; 1.
DR   InterPro; IPR004825; Insulin.
DR   InterPro; IPR016179; Insulin-like.
DR   InterPro; IPR036438; Insulin-like_sf.
DR   InterPro; IPR022353; Insulin_CS.
DR   InterPro; IPR022352; Insulin_family.
DR   PANTHER; PTHR11454; PTHR11454; 1.
DR   Pfam; PF00049; Insulin; 1.
DR   PRINTS; PR00277; INSULIN.
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   Carbohydrate metabolism; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Disulfide bond; Glucose metabolism; Hormone;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000269|PubMed:5949593"
FT   PEPTIDE         25..54
FT                   /note="Insulin B chain"
FT                   /id="PRO_0000015777"
FT   PROPEP          57..87
FT                   /note="C peptide"
FT                   /id="PRO_0000015778"
FT   PEPTIDE         90..110
FT                   /note="Insulin A chain"
FT                   /id="PRO_0000015779"
FT   DISULFID        31..96
FT                   /note="Interchain (between B and A chains)"
FT                   /evidence="ECO:0000250|UniProtKB:P01308"
FT   DISULFID        43..109
FT                   /note="Interchain (between B and A chains)"
FT                   /evidence="ECO:0000250|UniProtKB:P01308"
FT   DISULFID        95..100
FT                   /evidence="ECO:0000250|UniProtKB:P01308"
SQ   SEQUENCE   110 AA;  12190 MW;  A574791864A4FB98 CRC64;
     MALWMRLLPL LALLALWAPA PTRAFVNQHL CGSHLVEALY LVCGERGFFY TPKARREVED
     LQVRDVELAG APGEGGLQPL ALEGALQKRG IVEQCCTSIC SLYQLENYCN