ID SECR_MOUSE Reviewed; 133 AA. AC Q08535; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1994, sequence version 1. DT 24-JAN-2024, entry version 142. DE RecName: Full=Secretin {ECO:0000303|PubMed:8179583}; DE Flags: Precursor; GN Name=Sct {ECO:0000312|MGI:MGI:99466}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8179583; DOI=10.1006/bbrc.1994.1558; RA Lan M.S., Kajiyama W., Donadel G., Lu J., Notkins A.L.; RT "cDNA sequence and genomic organization of mouse secretin."; RL Biochem. Biophys. Res. Commun. 200:1066-1071(1994). RN [2] RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=18534766; DOI=10.1016/j.neuroscience.2008.04.037; RA Yamagata T., Urano H., Weeber E.J., Nelson D.L., Nishijima I.; RT "Impaired hippocampal synaptic function in secretin deficient mice."; RL Neuroscience 154:1417-1422(2008). RN [3] RP FUNCTION. RX PubMed=20578263; DOI=10.1002/hep.23657; RA Glaser S., Lam I.P., Franchitto A., Gaudio E., Onori P., Chow B.K., RA Wise C., Kopriva S., Venter J., White M., Ueno Y., Dostal D., Carpino G., RA Mancinelli R., Butler W., Chiasson V., DeMorrow S., Francis H., Alpini G.; RT "Knockout of secretin receptor reduces large cholangiocyte hyperplasia in RT mice with extrahepatic cholestasis induced by bile duct ligation."; RL Hepatology 52:204-214(2010). RN [4] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=21159798; DOI=10.1093/hmg/ddq545; RA Jukkola P.I., Rogers J.T., Kaspar B.K., Weeber E.J., Nishijima I.; RT "Secretin deficiency causes impairment in survival of neural progenitor RT cells in mice."; RL Hum. Mol. Genet. 20:1000-1007(2011). RN [5] RP FUNCTION. RX PubMed=20739612; DOI=10.1096/fj.10-165399; RA Lee V.H., Lee L.T., Chu J.Y., Lam I.P., Siu F.K., Vaudry H., Chow B.K.; RT "An indispensable role of secretin in mediating the osmoregulatory RT functions of angiotensin II."; RL FASEB J. 24:5024-5032(2010). RN [6] RP FUNCTION. RX PubMed=20927047; DOI=10.1038/npp.2010.178; RA Cheng C.Y., Chu J.Y., Chow B.K.; RT "Central and peripheral administration of secretin inhibits food intake in RT mice through the activation of the melanocortin system."; RL Neuropsychopharmacology 36:459-471(2011). RN [7] RP FUNCTION. RX PubMed=24273196; DOI=10.1194/jlr.m038042; RA Sekar R., Chow B.K.; RT "Lipolytic actions of secretin in mouse adipocytes."; RL J. Lipid Res. 55:190-200(2014). RN [8] RP FUNCTION. RX PubMed=30449620; DOI=10.1016/j.cell.2018.10.016; RA Li Y., Schnabl K., Gabler S.M., Willershaeuser M., Reber J., Karlas A., RA Laurila S., Lahesmaa M., U Din M., Bast-Habersbrunner A., Virtanen K.A., RA Fromme T., Bolze F., O'Farrell L.S., Alsina-Fernandez J., Coskun T., RA Ntziachristos V., Nuutila P., Klingenspor M.; RT "Secretin-activated brown fat mediates prandial thermogenesis to induce RT satiation."; RL Cell 175:1561-1574(2018). CC -!- FUNCTION: Hormone involved in different processes, such as regulation CC of the pH of the duodenal content, food intake and water homeostasis CC (PubMed:20578263, PubMed:20739612, PubMed:20927047, PubMed:30449620). CC Exerts its biological effects by binding to secretin receptor (SCTR), a CC G-protein coupled receptor expressed in the basolateral domain of CC several cells (PubMed:30449620). Acts as a key gastrointestinal hormone CC by regulating the pH of the duodenal content (PubMed:20578263). CC Secreted by S cells of the duodenum in the crypts of Lieberkuehn and CC regulates the pH of the duodenum by (1) inhibiting the secretion of CC gastric acid from the parietal cells of the stomach and (2) stimulating CC the production of bicarbonate (NaHCO(3)) from the ductal cells of the CC pancreas (PubMed:20578263). Production of bicarbonate is essential to CC neutralize the pH and ensure no damage is done to the small intestine CC by the gastric acid (PubMed:20578263). In addition to regulating the pH CC of the duodenal content, plays a central role in diet induced CC thermogenesis: acts as a non-sympathetic brown fat (BAT) activator CC mediating prandial thermogenesis, which consequentially induces CC satiation (PubMed:30449620). Mechanistically, secretin released by the CC gut after a meal binds to secretin receptor (SCTR) in brown adipocytes, CC activating brown fat thermogenesis by stimulating lipolysis, which is CC sensed in the brain and promotes satiation (PubMed:30449620). Also able CC to stimulate lipolysis in white adipocytes (PubMed:24273196). Also CC plays an important role in cellular osmoregulation: released into the CC systemic circulation in response to hyperosmolality and acts at CC different levels in the hypothalamus, pituitary and kidney to regulate CC water homeostasis (PubMed:20739612). Also plays a role in the central CC nervous system, possibly by acting as a neuropeptide hormone: required CC for hippocampal synaptic function and neural progenitor cells CC maintenance (PubMed:18534766, PubMed:21159798). CC {ECO:0000269|PubMed:18534766, ECO:0000269|PubMed:20578263, CC ECO:0000269|PubMed:20739612, ECO:0000269|PubMed:20927047, CC ECO:0000269|PubMed:21159798, ECO:0000269|PubMed:24273196, CC ECO:0000269|PubMed:30449620}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P11384}. CC -!- TISSUE SPECIFICITY: Highly expressed in the intestine CC (PubMed:18534766). Also expressed in the hippocampus, cerebellum and CC the brain stem in adult mouse brain (PubMed:18534766). In the CC hippocampus, expressed in the dentate gyrus, the hilus and the CC molecular layer (PubMed:18534766). {ECO:0000269|PubMed:18534766}. CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile (PubMed:18534766). CC Mice however display impairment in synaptic plasticity in the CA1 area CC of the hippocampus (PubMed:18534766). Mice exhibit decreased neural CC progenitor cells in the subgranular zone of the dentate gyrus during CC the early postnatal period, leading to decreased volume of dentate CC gyrus, reduced long-term potentiation and impaired spatial learning CC ability in adults (PubMed:21159798). {ECO:0000269|PubMed:18534766, CC ECO:0000269|PubMed:21159798}. CC -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U07568; AAA18453.1; -; Unassigned_DNA. DR EMBL; X73580; CAA51982.1; -; mRNA. DR CCDS; CCDS40184.1; -. DR PIR; JC2202; JC2202. DR RefSeq; NP_035458.1; NM_011328.3. DR AlphaFoldDB; Q08535; -. DR SMR; Q08535; -. DR STRING; 10090.ENSMUSP00000041519; -. DR PhosphoSitePlus; Q08535; -. DR PaxDb; 10090-ENSMUSP00000041519; -. DR ProteomicsDB; 256767; -. DR Antibodypedia; 9839; 227 antibodies from 30 providers. DR Ensembl; ENSMUST00000167790.3; ENSMUSP00000128729.2; ENSMUSG00000038580.14. DR GeneID; 20287; -. DR KEGG; mmu:20287; -. DR UCSC; uc009kkl.2; mouse. DR AGR; MGI:99466; -. DR CTD; 6343; -. DR MGI; MGI:99466; Sct. DR VEuPathDB; HostDB:ENSMUSG00000038580; -. DR eggNOG; ENOG502R8F0; Eukaryota. DR GeneTree; ENSGT00390000002624; -. DR HOGENOM; CLU_1991937_0_0_1; -. DR InParanoid; Q08535; -. DR OMA; HAPFPWL; -. DR OrthoDB; 4605098at2759; -. DR PhylomeDB; Q08535; -. DR Reactome; R-MMU-418555; G alpha (s) signalling events. DR Reactome; R-MMU-420092; Glucagon-type ligand receptors. DR BioGRID-ORCS; 20287; 2 hits in 78 CRISPR screens. DR ChiTaRS; Sct; mouse. DR PRO; PR:Q08535; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; Q08535; Protein. DR Bgee; ENSMUSG00000038580; Expressed in placenta labyrinth and 93 other cell types or tissues. DR ExpressionAtlas; Q08535; baseline and differential. DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB. DR GO; GO:0046659; F:digestive hormone activity; ISS:UniProtKB. DR GO; GO:0001664; F:G protein-coupled receptor binding; ISO:MGI. DR GO; GO:0005179; F:hormone activity; ISS:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central. DR GO; GO:0007420; P:brain development; IBA:GO_Central. DR GO; GO:0021542; P:dentate gyrus development; IMP:MGI. DR GO; GO:0002024; P:diet induced thermogenesis; IDA:UniProtKB. DR GO; GO:0021766; P:hippocampus development; IMP:UniProtKB. DR GO; GO:0009992; P:intracellular water homeostasis; ISS:UniProtKB. DR GO; GO:1903640; P:negative regulation of gastrin-induced gastric acid secretion; ISO:MGI. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI. DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI. DR GO; GO:0097150; P:neuronal stem cell population maintenance; IMP:MGI. DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; ISO:MGI. DR GO; GO:0050996; P:positive regulation of lipid catabolic process; IDA:UniProtKB. DR GO; GO:0090187; P:positive regulation of pancreatic juice secretion; ISO:MGI. DR GO; GO:0090274; P:positive regulation of somatostatin secretion; ISO:MGI. DR GO; GO:0032098; P:regulation of appetite; IDA:UniProtKB. DR GO; GO:0048167; P:regulation of synaptic plasticity; IMP:UniProtKB. DR GO; GO:0031667; P:response to nutrient levels; IDA:UniProtKB. DR GO; GO:0008542; P:visual learning; IMP:MGI. DR InterPro; IPR000532; Glucagon_GIP_secretin_VIP. DR InterPro; IPR015675; Prosecretin. DR PANTHER; PTHR17378; SECRETIN; 1. DR PANTHER; PTHR17378:SF1; SECRETIN; 1. DR SMART; SM00070; GLUCA; 1. DR PROSITE; PS00260; GLUCAGON; 1. DR Genevisible; Q08535; MM. PE 2: Evidence at transcript level; KW Amidation; Cleavage on pair of basic residues; Hormone; Phosphoprotein; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..22 FT /evidence="ECO:0000255" FT PROPEP 23..30 FT /evidence="ECO:0000250|UniProtKB:P11384" FT /id="PRO_0000011426" FT PEPTIDE 32..58 FT /note="Secretin" FT /evidence="ECO:0000250|UniProtKB:P11384" FT /id="PRO_0000011427" FT PROPEP 62..133 FT /evidence="ECO:0000250|UniProtKB:P11384" FT /id="PRO_0000011428" FT MOD_RES 58 FT /note="Valine amide" FT /evidence="ECO:0000250|UniProtKB:P11384" FT MOD_RES 62 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11384" SQ SEQUENCE 133 AA; 14914 MW; 9B69CBCF74CA9709 CRC64; MEPPLPTPML LLLLLLLSSS AALPAPPRTP RHSDGMFTSE LSRLQDSARL QRLLQGLVGK RSEQDTENIP ENSLARSKPL EDQLCLLWSN TQTLQDWLLP RLSLDGSLSL WLPPGPRSAV DRSEWTETTR PPR //