SECR_PIG
ID SECR_PIG Reviewed; 134 AA.
AC P63298; A0A286ZRG5; P01279; Q9TR13;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 2.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Secretin {ECO:0000303|Ref.1};
DE Flags: Precursor;
GN Name=SCT {ECO:0000250|UniProtKB:P09683};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-134.
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 [3]
RP PROTEIN SEQUENCE OF 4-59 (PRECURSOR PROTEIN), AND SUBCELLULAR LOCATION.
RC TISSUE=Intestine;
RX PubMed=8618828; DOI=10.1073/pnas.92.26.11985;
RA Bonetto V., Joernvall H., Mutt V., Sillard R.;
RT "Two alternative processing pathways for a preprohormone: a bioactive form
RT of secretin.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:11985-11989(1995).
RN [4]
RP PROTEIN SEQUENCE OF 33-59, AND AMIDATION AT VAL-59.
RX PubMed=5465996; DOI=10.1111/j.1432-1033.1970.tb01034.x;
RA Mutt V., Jorpes J.E., Magnusson S.;
RT "Structure of porcine secretin. The amino acid sequence.";
RL Eur. J. Biochem. 15:513-519(1970).
RN [5]
RP PROTEIN SEQUENCE OF 33-62 AND 95-134 (PRECURSOR PROTEIN).
RX PubMed=2395872; DOI=10.1073/pnas.87.17.6781;
RA Gafvelin G., Joernvall H., Mutt V.;
RT "Processing of prosecretin: isolation of a secretin precursor from porcine
RT intestine.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:6781-6785(1990).
RN [6]
RP SYNTHESIS OF 33-134.
RX PubMed=5978238;
RA Bodanszky M., Ondetti M.A., Levine S.D., Narayanan V.L., Von Saltza M.,
RA Sheehan J.T., Williams N.J., Sabo E.F.;
RT "Synthesis of a heptacosapeptide amide with the hormonal activity of
RT secretin.";
RL Chem. Ind. 42:1757-1758(1966).
RN [7]
RP STRUCTURE BY NMR OF SECRETIN.
RX PubMed=2831051; DOI=10.1111/j.1432-1033.1988.tb13814.x;
RA Clore G.M., Nilges M., Bruenger A., Gronenborn A.M.;
RT "Determination of the backbone conformation of secretin by restrained
RT molecular dynamics on the basis of interproton distance data.";
RL Eur. J. Biochem. 171:479-484(1988).
RN [8]
RP STRUCTURE BY NMR OF SECRETIN.
RX PubMed=2883029; DOI=10.1016/0014-5793(87)80119-9;
RA Gronenborn A.M., Bovermann G., Clore G.M.;
RT "A 1H-NMR study of the solution conformation of secretin. Resonance
RT assignment and secondary structure.";
RL FEBS Lett. 215:88-94(1987).
CC -!- FUNCTION: Hormone involved in different processes, such as regulation
CC of the pH of the duodenal content, food intake and water homeostasis.
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. Acts as a key gastrointestinal hormone by regulating the
CC pH of the duodenal content. Secreted by S cells of the duodenum in the
CC crypts of Lieberkuehn and regulates the pH of the duodenum by (1)
CC inhibiting the secretion of gastric acid from the parietal cells of the
CC stomach and (2) stimulating the production of bicarbonate (NaHCO(3))
CC from the ductal cells of the pancreas (By similarity). Production of
CC bicarbonate is essential to neutralize the pH and ensure no damage is
CC done to the small intestine by the gastric acid. 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. Mechanistically, secretin released by the gut after
CC 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. Also able to stimulate
CC lipolysis in white adipocytes (By similarity). Also plays an important
CC role in cellular osmoregulation: released into the systemic circulation
CC in response to hyperosmolality and acts at different levels in the
CC hypothalamus, pituitary and kidney to regulate water homeostasis (By
CC similarity). Also plays a role in the central nervous system, possibly
CC by acting as a neuropeptide hormone: required for hippocampal synaptic
CC function and neural progenitor cells maintenance (By similarity).
CC {ECO:0000250|UniProtKB:P11384, ECO:0000250|UniProtKB:Q08535}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8618828}.
CC -!- PHARMACEUTICAL: Available under the name Secretin-Ferring (Ferring
CC Pharmaceuticals). Used for diagnostic use in pancreatic dysfunction.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AEMK02000006; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AEMK02000006; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M31496; AAA31121.1; -; mRNA.
DR PIR; B35094; SEPG.
DR RefSeq; XP_003122439.1; XM_003122391.3.
DR AlphaFoldDB; P63298; -.
DR BMRB; P63298; -.
DR SMR; P63298; -.
DR PRIDE; P63298; -.
DR GeneID; 397464; -.
DR KEGG; ssc:397464; -.
DR CTD; 6343; -.
DR InParanoid; P63298; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
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; IEA:Ensembl.
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:0009992; P:cellular water homeostasis; ISS:UniProtKB.
DR GO; GO:0002024; P:diet induced thermogenesis; ISS:UniProtKB.
DR GO; GO:0021766; P:hippocampus development; ISS:UniProtKB.
DR GO; GO:1903640; P:negative regulation of gastrin-induced gastric acid secretion; IBA:GO_Central.
DR GO; GO:0050996; P:positive regulation of lipid catabolic process; ISS:UniProtKB.
DR GO; GO:0090187; P:positive regulation of pancreatic juice secretion; IBA:GO_Central.
DR GO; GO:0090274; P:positive regulation of somatostatin secretion; IBA:GO_Central.
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 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; Pharmaceutical; Phosphoprotein; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..31
FT /evidence="ECO:0000269|PubMed:5465996"
FT /id="PRO_0000011429"
FT PEPTIDE 33..59
FT /note="Secretin"
FT /evidence="ECO:0000269|PubMed:5465996"
FT /id="PRO_0000011430"
FT PROPEP 63..134
FT /evidence="ECO:0000269|PubMed:5465996"
FT /id="PRO_0000011431"
FT MOD_RES 59
FT /note="Valine amide"
FT /evidence="ECO:0000269|PubMed:5465996"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11384"
SQ SEQUENCE 134 AA; 14581 MW; 8364E9B1A0F32AE2 CRC64;
MATRALLLLL LLPPLLLLAG CAARPAPPRA PRHSDGTFTS ELSRLRDSAR LQRLLQGLVG
KRSQQDPENN TAWTKSGEDR LCQLWSHMPA LQAWMPMKPP VDQAWSPWLP PGLRAGALVS
EPAIPAAEGS PMPP
