SECR_RAT
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 03-AUG-2022, entry version 137.
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:7958688, PubMed:8568688, PubMed:3047699, PubMed:9655680,
CC PubMed:19805236). 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:9506976, PubMed:12403838).
CC Acts as a key gastrointestinal hormone by regulating the pH of the
CC duodenal content (PubMed:7958688, PubMed:8568688, PubMed:3047699,
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:7958688, PubMed:8568688,
CC PubMed:3047699, 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}.
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; 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_022670.2.
DR RefSeq; XP_006230580.1; XM_006230518.3.
DR AlphaFoldDB; P11384; -.
DR SMR; P11384; -.
DR STRING; 10116.ENSRNOP00000024094; -.
DR iPTMnet; P11384; -.
DR PhosphoSitePlus; P11384; -.
DR PaxDb; P11384; -.
DR Ensembl; ENSRNOT00000024094; ENSRNOP00000024094; ENSRNOG00000017873.
DR GeneID; 24769; -.
DR KEGG; rno:24769; -.
DR UCSC; RGD:3643; rat.
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; MPLGGAW; -.
DR OrthoDB; 1524218at2759; -.
DR PhylomeDB; P11384; -.
DR TreeFam; TF338215; -.
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 tissues.
DR Genevisible; P11384; RN.
DR GO; GO:0005615; C:extracellular space; 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:0047485; F:protein N-terminus binding; IPI:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IPI:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0009992; P:cellular water homeostasis; IDA:UniProtKB.
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: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:0043950; P:positive regulation of cAMP-mediated signaling; 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; PTHR17378; 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
