SECR_MOUSE
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 03-AUG-2022, entry version 134.
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}.
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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; Q08535; -.
DR PRIDE; Q08535; -.
DR ProteomicsDB; 256767; -.
DR Antibodypedia; 9839; 202 antibodies from 30 providers.
DR Ensembl; ENSMUST00000167790; ENSMUSP00000128729; ENSMUSG00000038580.
DR GeneID; 20287; -.
DR KEGG; mmu:20287; -.
DR UCSC; uc009kkl.2; mouse.
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; MPLGGAW; -.
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 73 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 90 other tissues.
DR ExpressionAtlas; Q08535; baseline and differential.
DR Genevisible; Q08535; MM.
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:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0007420; P:brain development; IBA:GO_Central.
DR GO; GO:0009992; P:cellular water homeostasis; ISS:UniProtKB.
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: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; PTHR17378; 1.
DR Pfam; PF00123; Hormone_2; 1.
DR SMART; SM00070; GLUCA; 1.
DR PROSITE; PS00260; GLUCAGON; 1.
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
