SECR_HUMAN
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 03-AUG-2022, entry version 171.
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).
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). Acts as a key
CC gastrointestinal hormone by regulating the pH of the duodenal content
CC (By similarity). 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 (By similarity). Production of bicarbonate
CC is essential to neutralize the pH and ensure no damage is done to the
CC small 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 (Probable). 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 (By similarity). Also able
CC to stimulate lipolysis in white adipocytes (By similarity). Also plays
CC 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P11384,
CC ECO:0000250|UniProtKB:Q08535, ECO:0000303|PubMed:25332973,
CC 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_021920.3.
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 PDBsum; 6WI9; -.
DR PDBsum; 6WZG; -.
DR PDBsum; 7D3S; -.
DR AlphaFoldDB; P09683; -.
DR SMR; P09683; -.
DR BioGRID; 112247; 6.
DR IntAct; P09683; 4.
DR STRING; 9606.ENSP00000176195; -.
DR PhosphoSitePlus; P09683; -.
DR BioMuta; SCT; -.
DR DMDM; 12231018; -.
DR MassIVE; P09683; -.
DR PaxDb; P09683; -.
DR PeptideAtlas; P09683; -.
DR PRIDE; P09683; -.
DR ProteomicsDB; 52265; -.
DR Antibodypedia; 9839; 202 antibodies from 30 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 CTD; 6343; -.
DR DisGeNET; 6343; -.
DR GeneCards; SCT; -.
DR HGNC; HGNC:10607; SCT.
DR HPA; ENSG00000070031; Tissue enriched (intestine).
DR MIM; 182099; gene.
DR neXtProt; NX_P09683; -.
DR OpenTargets; ENSG00000070031; -.
DR PharmGKB; PA35017; -.
DR VEuPathDB; HostDB:ENSG00000070031; -.
DR eggNOG; ENOG502R8F0; Eukaryota.
DR GeneTree; ENSGT00390000002624; -.
DR HOGENOM; CLU_1991937_0_0_1; -.
DR InParanoid; P09683; -.
DR OMA; MPLGGAW; -.
DR OrthoDB; 1524218at2759; -.
DR PhylomeDB; P09683; -.
DR TreeFam; TF338215; -.
DR PathwayCommons; P09683; -.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-420092; Glucagon-type ligand receptors.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P09683; -.
DR BioGRID-ORCS; 6343; 11 hits in 1065 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 88 other tissues.
DR Genevisible; P09683; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
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; IPI:GO_Central.
DR GO; GO:0005179; F:hormone activity; ISS:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
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:0048566; P:embryonic digestive tract development; IEA:Ensembl.
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:0030157; P:pancreatic juice secretion; NAS:UniProtKB.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; 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; 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 3D-structure; Amidation; Cleavage on pair of basic residues;
KW Direct protein sequencing; Hormone; Phosphoprotein; Reference proteome;
KW 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
