ID   SECR_RAT                Reviewed;         134 AA.
AC   P11384;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1990, sequence version 2.
DT   02-SEP-2026, entry version 153.
DE   RecName: Full=Secretin {ECO:0000303|PubMed:2315322};
DE   Flags: Precursor;
GN   Name=Sct {ECO:0000312|RGD:3643};
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 [MRNA].
RX   PubMed=2315322; DOI=10.1073/pnas.87.6.2299;
RA   Kopin A.S., Wheeler M.B., Leiter A.B.;
RT   "Secretin: structure of the precursor and tissue distribution of the
RT   mRNA.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:2299-2303(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1711228; DOI=10.1073/pnas.88.12.5335;
RA   Kopin A.S., Wheeler M.B., Nishitani J., McBride E.W., Chang T.M.,
RA   Chey W.Y., Leiter A.B.;
RT   "The secretin gene: evolutionary history, alternative splicing, and
RT   developmental regulation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:5335-5339(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Brain;
RX   PubMed=2061329; DOI=10.1016/s0021-9258(18)98940-4;
RA   Itoh N., Furuya T., Ozaki K., Kawasaki T.;
RT   "The secretin precursor gene. Structure of the coding region and expression
RT   in the brain.";
RL   J. Biol. Chem. 266:12595-12598(1991).
RN   [4]
RP   PROTEIN SEQUENCE OF 33-59, AND AMIDATION AT VAL-59.
RX   PubMed=2719704; DOI=10.1016/0006-291x(89)92514-x;
RA   Gossen D., Vandermeers A., Vandermeers-Piret M.-C., Rathe J., Cauvin A.,
RA   Robberecht P., Christophe J.;
RT   "Isolation and primary structure of rat secretin.";
RL   Biochem. Biophys. Res. Commun. 160:862-867(1989).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-63, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [6]
RP   FUNCTION.
RX   PubMed=7958688; DOI=10.1016/0016-5085(94)90817-6;
RA   Chung I., Li P., Lee K., Chang T., Chey W.Y.;
RT   "Dual inhibitory mechanism of secretin action on acid secretion in totally
RT   isolated, vascularly perfused rat stomach.";
RL   Gastroenterology 107:1751-1758(1994).
RN   [7]
RP   FUNCTION.
RX   PubMed=8568688; DOI=10.1113/jphysiol.1995.sp020984;
RA   Shimizu K., Li P., Lee K.Y., Chang T.M., Chey W.Y.;
RT   "The mechanism of inhibitory action of secretin on gastric acid secretion
RT   in conscious rats.";
RL   J. Physiol. (Lond.) 488:501-508(1995).
RN   [8]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=3047699; DOI=10.1016/0196-9781(88)90168-4;
RA   Murthy S.N., Ganiban G.;
RT   "Effect of the secretin family of peptides on gastric emptying and small
RT   intestinal transit in rats.";
RL   Peptides 9:583-588(1988).
RN   [9]
RP   FUNCTION.
RX   PubMed=9655680; DOI=10.1152/ajpgi.1998.275.1.g22;
RA   Li P., Chang T.M., Chey W.Y.;
RT   "Secretin inhibits gastric acid secretion via a vagal afferent pathway in
RT   rats.";
RL   Am. J. Physiol. 275:G22-G28(1998).
RN   [10]
RP   FUNCTION.
RX   PubMed=9506976; DOI=10.1074/jbc.273.12.6756;
RA   Shetzline M.A., Premont R.T., Walker J.K., Vigna S.R., Caron M.G.;
RT   "A role for receptor kinases in the regulation of class II G protein-
RT   coupled receptors. Phosphorylation and desensitization of the secretin
RT   receptor.";
RL   J. Biol. Chem. 273:6756-6762(1998).
RN   [11]
RP   FUNCTION.
RX   PubMed=12403838; DOI=10.1210/me.2002-0111;
RA   Dong M., Zang M., Pinon D.I., Li Z., Lybrand T.P., Miller L.J.;
RT   "Interaction among four residues distributed through the secretin
RT   pharmacophore and a focused region of the secretin receptor amino
RT   terminus.";
RL   Mol. Endocrinol. 16:2490-2501(2002).
RN   [12]
RP   TISSUE SPECIFICITY.
RX   PubMed=15276242; DOI=10.1016/j.neulet.2004.05.030;
RA   Tay J., Goulet M., Rusche J., Boismenu R.;
RT   "Age-related and regional differences in secretin and secretin receptor
RT   mRNA levels in the rat brain.";
RL   Neurosci. Lett. 366:176-181(2004).
RN   [13]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=19805236; DOI=10.1073/pnas.0903695106;
RA   Chu J.Y., Lee L.T., Lai C.H., Vaudry H., Chan Y.S., Yung W.H., Chow B.K.;
RT   "Secretin as a neurohypophysial factor regulating body water homeostasis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:15961-15966(2009).
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:19805236, PubMed:3047699, PubMed:7958688, PubMed:8568688,
CC       PubMed:9655680). Exerts its biological effects by binding to secretin
CC       receptor (SCTR), a G protein-coupled receptor expressed in the
CC       basolateral domain of several cells (PubMed:12403838, PubMed:9506976).
CC       Acts as a key gastrointestinal hormone by regulating the pH of the
CC       duodenal content (PubMed:3047699, PubMed:7958688, PubMed:8568688,
CC       PubMed:9655680). Secreted by S cells of the duodenum in the crypts of
CC       Lieberkuehn and regulates the pH of the duodenum by (1) inhibiting the
CC       secretion of gastric acid from the parietal cells of the stomach and
CC       (2) stimulating the production of bicarbonate (NaHCO(3)) from the
CC       ductal cells of the pancreas (PubMed:3047699, PubMed:7958688,
CC       PubMed:8568688, PubMed:9655680). Production of bicarbonate is essential
CC       to neutralize the pH and ensure no damage is done to the small
CC       intestine by the gastric acid (By similarity). In addition to
CC       regulating the pH of the duodenal content, plays a central role in diet
CC       induced thermogenesis: acts as a non-sympathetic brown fat (BAT)
CC       activator mediating prandial thermogenesis, which consequentially
CC       induces satiation (By similarity). Mechanistically, secretin released
CC       by the gut after a meal binds to secretin receptor (SCTR) in brown
CC       adipocytes, activating brown fat thermogenesis by stimulating
CC       lipolysis, which is sensed in the brain and promotes satiation (By
CC       similarity). Also able to stimulate lipolysis in white adipocytes (By
CC       similarity). Also plays an important role in cellular osmoregulation:
CC       released into the systemic circulation in response to hyperosmolality
CC       and acts at different levels in the hypothalamus, pituitary and kidney
CC       to regulate water homeostasis (PubMed:19805236). Also plays a role in
CC       the central nervous system, possibly by acting as a neuropeptide
CC       hormone: required for hippocampal synaptic function and neural
CC       progenitor cells maintenance (By similarity).
CC       {ECO:0000250|UniProtKB:Q08535, ECO:0000269|PubMed:12403838,
CC       ECO:0000269|PubMed:19805236, ECO:0000269|PubMed:3047699,
CC       ECO:0000269|PubMed:7958688, ECO:0000269|PubMed:8568688,
CC       ECO:0000269|PubMed:9506976, ECO:0000269|PubMed:9655680}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19805236,
CC       ECO:0000269|PubMed:3047699}.
CC   -!- TISSUE SPECIFICITY: In the brain, expressed in the central amygdala,
CC       hippocampus, area postrema, nucleus of the tractus solitary and
CC       cerebellum (PubMed:15276242). Expressed at higher level in the
CC       cerebellum (PubMed:15276242). {ECO:0000269|PubMed:15276242}.
CC   -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
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DR   EMBL; M31495; AAA42126.1; -; mRNA.
DR   EMBL; M64033; AAA42128.1; -; Genomic_DNA.
DR   EMBL; M63984; AAA42127.1; -; Genomic_DNA.
DR   PIR; A40886; A40959.
DR   RefSeq; NP_073161.1; NM_022670.3.
DR   AlphaFoldDB; P11384; -.
DR   SMR; P11384; -.
DR   FunCoup; P11384; 51.
DR   STRING; 10116.ENSRNOP00000024094; -.
DR   GlyGen; P11384; 1 site.
DR   iPTMnet; P11384; -.
DR   PhosphoSitePlus; P11384; -.
DR   PaxDb; 10116-ENSRNOP00000024094; -.
DR   Ensembl; ENSRNOT00000024094.7; ENSRNOP00000024094.2; ENSRNOG00000017873.9.
DR   Ensembl; ENSRNOT00055004527; ENSRNOP00055003351; ENSRNOG00055002900.
DR   Ensembl; ENSRNOT00055050835; ENSRNOP00055041882; ENSRNOG00055029333.
DR   Ensembl; ENSRNOT00060057332; ENSRNOP00060047389; ENSRNOG00060033051.
DR   Ensembl; ENSRNOT00065032470; ENSRNOP00065025919; ENSRNOG00065019290.
DR   GeneID; 24769; -.
DR   KEGG; rno:24769; -.
DR   UCSC; RGD:3643; rat.
DR   AGR; RGD:3643; -.
DR   CTD; 6343; -.
DR   RGD; 3643; Sct.
DR   eggNOG; ENOG502R8F0; Eukaryota.
DR   GeneTree; ENSGT00390000002624; -.
DR   HOGENOM; CLU_1991937_0_0_1; -.
DR   InParanoid; P11384; -.
DR   OMA; HAPFPWL; -.
DR   OrthoDB; 9417777at2759; -.
DR   PhylomeDB; P11384; -.
DR   Reactome; R-RNO-420092; Glucagon-type ligand receptors.
DR   PRO; PR:P11384; -.
DR   Proteomes; UP000002494; Chromosome 1.
DR   Bgee; ENSRNOG00000017873; Expressed in duodenum and 13 other cell types or tissues.
DR   ExpressionAtlas; P11384; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0046659; F:digestive hormone activity; IDA:UniProtKB.
DR   GO; GO:0001664; F:G protein-coupled receptor binding; ISO:RGD.
DR   GO; GO:0005179; F:hormone activity; IDA:UniProtKB.
DR   GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0007420; P:brain development; IBA:GO_Central.
DR   GO; GO:0021542; P:dentate gyrus development; ISO:RGD.
DR   GO; GO:0002024; P:diet induced thermogenesis; ISS:UniProtKB.
DR   GO; GO:0048566; P:embryonic digestive tract development; IEP:RGD.
DR   GO; GO:0021766; P:hippocampus development; ISS:UniProtKB.
DR   GO; GO:0009992; P:intracellular water homeostasis; IDA:UniProtKB.
DR   GO; GO:1903640; P:negative regulation of gastrin-induced gastric acid secretion; IDA:RGD.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR   GO; GO:0097150; P:neuronal stem cell population maintenance; ISO:RGD.
DR   GO; GO:0141163; P:positive regulation of cAMP/PKA signal transduction; IDA:RGD.
DR   GO; GO:0050996; P:positive regulation of lipid catabolic process; ISS:UniProtKB.
DR   GO; GO:0090187; P:positive regulation of pancreatic juice secretion; IDA:RGD.
DR   GO; GO:0090274; P:positive regulation of somatostatin secretion; IDA:RGD.
DR   GO; GO:0032098; P:regulation of appetite; ISS:UniProtKB.
DR   GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
DR   GO; GO:0031667; P:response to nutrient levels; ISS:UniProtKB.
DR   GO; GO:0008542; P:visual learning; ISO:RGD.
DR   InterPro; IPR000532; Glucagon_GIP_secretin_VIP.
DR   InterPro; IPR015675; Prosecretin.
DR   PANTHER; PTHR17378; SECRETIN; 1.
DR   PANTHER; PTHR17378:SF1; SECRETIN; 1.
DR   Pfam; PF00123; Hormone_2; 1.
DR   SMART; SM00070; GLUCA; 1.
DR   PROSITE; PS00260; GLUCAGON; 1.
PE   1: Evidence at protein level;
KW   Amidation; Cleavage on pair of basic residues; Direct protein sequencing;
KW   Hormone; Phosphoprotein; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   PROPEP          22..31
FT                   /evidence="ECO:0000269|PubMed:2719704"
FT                   /id="PRO_0000011432"
FT   PEPTIDE         33..59
FT                   /note="Secretin"
FT                   /evidence="ECO:0000269|PubMed:2719704"
FT                   /id="PRO_0000011433"
FT   PROPEP          63..134
FT                   /evidence="ECO:0000269|PubMed:2719704"
FT                   /id="PRO_0000011434"
FT   MOD_RES         59
FT                   /note="Valine amide"
FT                   /evidence="ECO:0000269|PubMed:2719704"
FT   MOD_RES         63
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
SQ   SEQUENCE   134 AA;  15072 MW;  D9FA1A4C1F7C86E6 CRC64;
     MEPLLPTPPL LLLLLLLLSS SFVLPAPPRT PRHSDGTFTS ELSRLQDSAR LQRLLQGLVG
     KRSEEDTENI PENSVARPKP LEDQLCLLWS NTQALQDWLL PRLSLDGSLS LWLPPGPRPA
     VDHSEWTETT RQPR
//