ID   SECR_HUMAN              Reviewed;         121 AA.
AC   P09683;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2001, sequence version 2.
DT   02-SEP-2026, entry version 189.
DE   RecName: Full=Secretin {ECO:0000303|PubMed:11060443};
DE   Flags: Precursor;
GN   Name=SCT {ECO:0000303|PubMed:11060443, ECO:0000312|HGNC:HGNC:10607};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=11060443; DOI=10.1159/000015658;
RA   Whitmore T.E., Holloway J.L., Lofton-Day C.E., Maurer M.F., Chen L.,
RA   Quinton T.J., Vincent J.B., Scherer S.W., Lok S.;
RT   "Human secretin (SCT): gene structure, chromosome location, and
RT   distribution of mRNA.";
RL   Cytogenet. Cell Genet. 90:47-52(2000).
RN   [2]
RP   PROTEIN SEQUENCE OF 28-54, SUBCELLULAR LOCATION, AND AMIDATION AT VAL-54.
RA   Carlquist M., Joernvall H., Forssmann W.-G., Thulin L., Johansson C.,
RA   Mutt V.;
RT   "Human secretin is not identical to the porcine/bovine hormone.";
RL   IRCS Med. Sci. 13:217-218(1985).
RN   [3]
RP   REVIEW.
RX   PubMed=25332973; DOI=10.3978/j.issn.2305-5839.2012.12.01;
RA   Afroze S., Meng F., Jensen K., McDaniel K., Rahal K., Onori P., Gaudio E.,
RA   Alpini G., Glaser S.S.;
RT   "The physiological roles of secretin and its receptor.";
RL   Ann. Transl. Med. 1:29-29(2013).
RN   [4]
RP   FUNCTION, AND INDUCTION.
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).
RN   [5] {ECO:0007744|PDB:7D3S}
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 28-54 IN COMPLEX WITH
RP   SCTR, AND FUNCTION.
RX   PubMed=33008599; DOI=10.1016/j.bbrc.2020.08.042;
RA   Fukuhara S., Kobayashi K., Kusakizako T., Iida W., Kato M., Shihoya W.,
RA   Nureki O.;
RT   "Structure of the human secretin receptor coupled to an engineered
RT   heterotrimeric G protein.";
RL   Biochem. Biophys. Res. Commun. 533:861-866(2020).
RN   [6] {ECO:0007744|PDB:6WI9, ECO:0007744|PDB:6WZG}
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.30 ANGSTROMS) OF 28-54 IN COMPLEX WITH
RP   SCTR, AND FUNCTION.
RX   PubMed=32811827; DOI=10.1038/s41467-020-17791-4;
RA   Dong M., Deganutti G., Piper S.J., Liang Y.L., Khoshouei M.,
RA   Belousoff M.J., Harikumar K.G., Reynolds C.A., Glukhova A., Furness S.G.B.,
RA   Christopoulos A., Danev R., Wootten D., Sexton P.M., Miller L.J.;
RT   "Structure and dynamics of the active Gs-coupled human secretin receptor.";
RL   Nat. Commun. 11:4137-4137(2020).
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:25332973). 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:25332973, PubMed:33008599,
CC       PubMed:32811827). Acts as a key gastrointestinal hormone by regulating
CC       the pH of the duodenal content (By similarity). Secreted by S cells of
CC       the duodenum in the crypts of Lieberkuehn and regulates the pH of the
CC       duodenum by (1) inhibiting the secretion of gastric acid from the
CC       parietal cells of the stomach and (2) stimulating the production of
CC       bicarbonate (NaHCO(3)) from the ductal cells of the pancreas (By
CC       similarity). Production of bicarbonate is essential to neutralize the
CC       pH and ensure no damage is done to the small intestine by the gastric
CC       acid (By similarity). In addition to regulating the pH of the duodenal
CC       content, plays a central role in diet induced thermogenesis: acts as a
CC       non-sympathetic brown fat (BAT) activator mediating prandial
CC       thermogenesis, which consequentially induces satiation (Probable).
CC       Mechanistically, secretin released by the gut after a meal binds to
CC       secretin receptor (SCTR) in brown adipocytes, activating brown fat
CC       thermogenesis by stimulating lipolysis, which is sensed in the brain
CC       and promotes satiation (By similarity). 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       ECO:0000269|PubMed:32811827, ECO:0000269|PubMed:33008599,
CC       ECO:0000303|PubMed:25332973, ECO:0000305|PubMed:30449620}.
CC   -!- INTERACTION:
CC       P09683; O14964: HGS; NbExp=3; IntAct=EBI-12844598, EBI-740220;
CC       P09683; P49639: HOXA1; NbExp=3; IntAct=EBI-12844598, EBI-740785;
CC       P09683; O14770-4: MEIS2; NbExp=3; IntAct=EBI-12844598, EBI-8025850;
CC       P09683; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-12844598, EBI-739895;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.2}.
CC   -!- INDUCTION: Serum secretin levels are increased after single-meal
CC       ingestion. {ECO:0000269|PubMed:30449620}.
CC   -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Secretin entry;
CC       URL="https://en.wikipedia.org/wiki/Secretin";
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DR   EMBL; AF244355; AAG31443.1; -; Genomic_DNA.
DR   CCDS; CCDS7709.1; -.
DR   RefSeq; NP_068739.1; NM_021920.4.
DR   PDB; 6WI9; EM; 4.30 A; P=28-54.
DR   PDB; 6WZG; EM; 2.30 A; P=28-54.
DR   PDB; 7D3S; EM; 2.90 A; P=28-54.
DR   AlphaFoldDB; P09683; -.
DR   EMDB; EMD-21683; -.
DR   EMDB; EMD-21972; -.
DR   EMDB; EMD-30566; -.
DR   SMR; P09683; -.
DR   BioGRID; 112247; 6.
DR   CORUM; P09683; -.
DR   FunCoup; P09683; 370.
DR   IntAct; P09683; 4.
DR   STRING; 9606.ENSP00000176195; -.
DR   DrugBank; DB09532; Secretin human.
DR   PhosphoSitePlus; P09683; -.
DR   BioMuta; SCT; -.
DR   DMDM; 12231018; -.
DR   MassIVE; P09683; -.
DR   PaxDb; 9606-ENSP00000176195; -.
DR   PeptideAtlas; P09683; -.
DR   Antibodypedia; 9839; 199 antibodies from 32 providers.
DR   DNASU; 6343; -.
DR   Ensembl; ENST00000176195.4; ENSP00000176195.3; ENSG00000070031.4.
DR   Ensembl; ENST00000622382.2; ENSP00000483559.1; ENSG00000274473.2.
DR   GeneID; 6343; -.
DR   KEGG; hsa:6343; -.
DR   MANE-Select; ENST00000176195.4; ENSP00000176195.3; NM_021920.4; NP_068739.1.
DR   UCSC; uc001lqo.2; human.
DR   AGR; HGNC:10607; -.
DR   ClinPGx; PA35017; -.
DR   CTD; 6343; -.
DR   DisGeNET; 6343; -.
DR   GeneCards; SCT; -.
DR   HGNC; HGNC:10607; SCT.
DR   HPA; ENSG00000070031; Tissue enriched (intestine).
DR   MIM; 182099; gene.
DR   OpenTargets; ENSG00000070031; -.
DR   VEuPathDB; HostDB:ENSG00000070031; -.
DR   eggNOG; ENOG502R8F0; Eukaryota.
DR   GeneTree; ENSGT00390000002624; -.
DR   HOGENOM; CLU_1991937_0_0_1; -.
DR   InParanoid; P09683; -.
DR   OMA; HAPFPWL; -.
DR   OrthoDB; 9417777at2759; -.
DR   PAN-GO; P09683; 6 GO annotations based on evolutionary models.
DR   PhylomeDB; P09683; -.
DR   PathwayCommons; P09683; -.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-420092; Glucagon-type ligand receptors.
DR   SignaLink; P09683; -.
DR   Agora; ENSG00000070031; -.
DR   BioGRID-ORCS; 6343; 14 hits in 1145 CRISPR screens.
DR   GeneWiki; Secretin; -.
DR   GenomeRNAi; 6343; -.
DR   Pharos; P09683; Tbio.
DR   PRO; PR:P09683; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P09683; protein.
DR   Bgee; ENSG00000070031; Expressed in duodenum and 89 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR   GO; GO:0046659; F:digestive hormone activity; ISS:UniProtKB.
DR   GO; GO:0001664; F:G protein-coupled receptor binding; IPI:GO_Central.
DR   GO; GO:0005179; F:hormone activity; ISS: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; IDA:UniProtKB.
DR   GO; GO:0007420; P:brain development; IBA:GO_Central.
DR   GO; GO:0002024; P:diet induced thermogenesis; ISS:UniProtKB.
DR   GO; GO:0048566; P:embryonic digestive tract development; IEA:Ensembl.
DR   GO; GO:0021766; P:hippocampus development; ISS:UniProtKB.
DR   GO; GO:0009992; P:intracellular water homeostasis; ISS:UniProtKB.
DR   GO; GO:1903640; P:negative regulation of gastrin-induced gastric acid secretion; IBA:GO_Central.
DR   GO; GO:0030157; P:pancreatic juice secretion; NAS:UniProtKB.
DR   GO; GO:0141163; P:positive regulation of cAMP/PKA signal transduction; IEA:Ensembl.
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; SECRETIN; 1.
DR   PANTHER; PTHR17378:SF1; SECRETIN; 1.
DR   Pfam; PF00123; Hormone_2; 1.
DR   SMART; SM00070; GLUCA; 1.
DR   PROSITE; PS00260; GLUCAGON; 1.
DR   PDBsum; 6WI9; -.
DR   PDBsum; 6WZG; -.
DR   PDBsum; 7D3S; -.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Hormone; Phosphoprotein;
KW   Proteomics identification; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   PROPEP          19..26
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="PRO_0000011423"
FT   PEPTIDE         28..54
FT                   /note="Secretin"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="PRO_0000011424"
FT   PROPEP          58..121
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="PRO_0000011425"
FT   MOD_RES         54
FT                   /note="Valine amide"
FT                   /evidence="ECO:0000269|Ref.2"
FT   MOD_RES         58
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P11384"
FT   HELIX           29..53
FT                   /evidence="ECO:0007829|PDB:6WZG"
SQ   SEQUENCE   121 AA;  13016 MW;  44BDB4EFC0E161CF CRC64;
     MAPRPLLLLL LLLGGSAARP APPRARRHSD GTFTSELSRL REGARLQRLL QGLVGKRSEQ
     DAENSMAWTR LSAGLLCPSG SNMPILQAWM PLDGTWSPWL PPGPMVSEPA GAAAEGTLRP
     R
//