INS2_RAT
ID INS2_RAT Reviewed; 110 AA.
AC P01323;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Insulin-2;
DE Contains:
DE RecName: Full=Insulin-2 B chain;
DE Contains:
DE RecName: Full=Insulin-2 A chain;
DE Flags: Precursor;
GN Name=Ins2; Synonyms=Ins-2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=498284; DOI=10.1016/0092-8674(79)90071-0;
RA Lomedico P., Rosenthal N., Efstratiadis A., Gilbert W., Kolodner R.,
RA Tizard R.;
RT "The structure and evolution of the two nonallelic rat preproinsulin
RT genes.";
RL Cell 18:545-558(1979).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2427930; DOI=10.1128/mcb.5.8.2090-2103.1985;
RA Soares M.B., Schin E., Henderson A., Karathanasis S.K., Cate R.,
RA Zeitlin S., Chirgwin J., Efstratiadis A.;
RT "RNA-mediated gene duplication: the rat preproinsulin I gene is a
RT functional retroposon.";
RL Mol. Cell. Biol. 5:2090-2103(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6249167; DOI=10.1111/j.1749-6632.1980.tb47271.x;
RA Lomedico P.T., Rosenthal N., Kolodner R., Efstratiadis A., Gilbert W.;
RT "The structure of rat preproinsulin genes.";
RL Ann. N. Y. Acad. Sci. 343:425-432(1980).
RN [4]
RP PROTEIN SEQUENCE OF 25-54 AND 90-110.
RX PubMed=4311938; DOI=10.1016/b978-0-12-571125-8.50008-9;
RA Steiner D.F., Clark J.L., Nolan C., Rubenstein A.H., Margoliash E.,
RA Aten B., Oyer P.E.;
RT "Proinsulin and the biosynthesis of insulin.";
RL Recent Prog. Horm. Res. 25:207-282(1969).
RN [5]
RP PROTEIN SEQUENCE OF 57-87.
RX PubMed=4640931; DOI=10.1016/s0021-9258(20)81791-8;
RA Tager H.S., Steiner D.F.;
RT "Primary structures of the proinsulin connecting peptides of the rat and
RT the horse.";
RL J. Biol. Chem. 247:7936-7940(1972).
RN [6]
RP PROTEIN SEQUENCE OF 57-87, AND SEQUENCE REVISION.
RX PubMed=4554104; DOI=10.1111/j.1432-1033.1972.tb01680.x;
RA Markussen J., Sundby F.;
RT "Rat-proinsulin C-peptides. Amino-acid sequences.";
RL Eur. J. Biochem. 25:153-162(1972).
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; V01243; CAA24560.1; -; Genomic_DNA.
DR EMBL; J00748; AAA41443.1; -; Genomic_DNA.
DR EMBL; M25585; AAA41440.1; -; Genomic_DNA.
DR EMBL; M25583; AAA41440.1; JOINED; Genomic_DNA.
DR PIR; B90789; IPRT2.
DR RefSeq; NP_062003.1; NM_019130.2.
DR AlphaFoldDB; P01323; -.
DR BioGRID; 246665; 1.
DR STRING; 10116.ENSRNOP00000027656; -.
DR PhosphoSitePlus; P01323; -.
DR PaxDb; P01323; -.
DR PRIDE; P01323; -.
DR Ensembl; ENSRNOT00000027656; ENSRNOP00000027656; ENSRNOG00000020405.
DR GeneID; 24506; -.
DR KEGG; rno:24506; -.
DR CTD; 16334; -.
DR RGD; 2916; Ins2.
DR eggNOG; ENOG502S5P5; Eukaryota.
DR GeneTree; ENSGT00390000015440; -.
DR HOGENOM; CLU_140421_1_0_1; -.
DR InParanoid; P01323; -.
DR OMA; LANQHLC; -.
DR OrthoDB; 1438615at2759; -.
DR PhylomeDB; P01323; -.
DR TreeFam; TF332820; -.
DR Reactome; R-RNO-264876; Insulin processing.
DR Reactome; R-RNO-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR Reactome; R-RNO-6807878; COPI-mediated anterograde transport.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-74713; IRS activation.
DR Reactome; R-RNO-74749; Signal attenuation.
DR Reactome; R-RNO-74751; Insulin receptor signalling cascade.
DR Reactome; R-RNO-74752; Signaling by Insulin receptor.
DR Reactome; R-RNO-77387; Insulin receptor recycling.
DR PRO; PR:P01323; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020405; Expressed in pancreas and 8 other tissues.
DR Genevisible; P01323; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0030141; C:secretory granule; ISO:RGD.
DR GO; GO:0005732; C:sno(s)RNA-containing ribonucleoprotein complex; ISO:RGD.
DR GO; GO:0005179; F:hormone activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005158; F:insulin receptor binding; ISO:RGD.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; ISO:RGD.
DR GO; GO:0002020; F:protease binding; ISO:RGD.
DR GO; GO:0032148; P:activation of protein kinase B activity; ISO:RGD.
DR GO; GO:0006953; P:acute-phase response; ISO:RGD.
DR GO; GO:0046631; P:alpha-beta T cell activation; ISO:RGD.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0006983; P:ER overload response; ISO:RGD.
DR GO; GO:0055089; P:fatty acid homeostasis; ISO:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0006006; P:glucose metabolic process; ISO:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISO:RGD.
DR GO; GO:0016042; P:lipid catabolic process; ISO:RGD.
DR GO; GO:0007520; P:myoblast fusion; ISO:RGD.
DR GO; GO:0014902; P:myotube differentiation; ISO:RGD.
DR GO; GO:0002674; P:negative regulation of acute inflammatory response; ISO:RGD.
DR GO; GO:0045922; P:negative regulation of fatty acid metabolic process; ISO:RGD.
DR GO; GO:2000252; P:negative regulation of feeding behavior; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0045818; P:negative regulation of glycogen catabolic process; ISO:RGD.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; ISO:RGD.
DR GO; GO:0033861; P:negative regulation of NAD(P)H oxidase activity; ISO:RGD.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISO:RGD.
DR GO; GO:0050709; P:negative regulation of protein secretion; ISO:RGD.
DR GO; GO:0045861; P:negative regulation of proteolysis; ISO:RGD.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; ISO:RGD.
DR GO; GO:0060266; P:negative regulation of respiratory burst involved in inflammatory response; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:1990535; P:neuron projection maintenance; ISO:RGD.
DR GO; GO:0038060; P:nitric oxide-cGMP-mediated signaling pathway; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:RGD.
DR GO; GO:1902952; P:positive regulation of dendritic spine maintenance; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0046326; P:positive regulation of glucose import; ISO:RGD.
DR GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISO:RGD.
DR GO; GO:0045821; P:positive regulation of glycolytic process; ISO:RGD.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISO:RGD.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:0010750; P:positive regulation of nitric oxide mediated signal transduction; ISO:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISO:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:RGD.
DR GO; GO:0050714; P:positive regulation of protein secretion; IBA:GO_Central.
DR GO; GO:0060267; P:positive regulation of respiratory burst; ISO:RGD.
DR GO; GO:0006521; P:regulation of cellular amino acid metabolic process; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0042325; P:regulation of phosphorylation; ISO:RGD.
DR GO; GO:0043393; P:regulation of protein binding; ISO:RGD.
DR GO; GO:0032880; P:regulation of protein localization; ISO:RGD.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0050708; P:regulation of protein secretion; ISO:RGD.
DR GO; GO:0022898; P:regulation of transmembrane transporter activity; ISO:RGD.
DR GO; GO:0042311; P:vasodilation; ISO:RGD.
DR GO; GO:0042060; P:wound healing; ISO:RGD.
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:4311938"
FT PEPTIDE 25..54
FT /note="Insulin-2 B chain"
FT /evidence="ECO:0000269|PubMed:498284"
FT /id="PRO_0000015898"
FT PROPEP 57..87
FT /note="C peptide"
FT /id="PRO_0000015899"
FT PEPTIDE 90..110
FT /note="Insulin-2 A chain"
FT /evidence="ECO:0000269|PubMed:498284"
FT /id="PRO_0000015900"
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:0000269|PubMed:4311938"
SQ SEQUENCE 110 AA; 12339 MW; 3A626DA98C86F3CA CRC64;
MALWIRFLPL LALLILWEPR PAQAFVKQHL CGSHLVEALY LVCGERGFFY TPMSRREVED
PQVAQLELGG GPGAGDLQTL ALEVARQKRG IVDQCCTSIC SLYQLENYCN
