ID   SCTR_RAT                Reviewed;         449 AA.
AC   P23811;
DT   01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1991, sequence version 1.
DT   24-JAN-2024, entry version 129.
DE   RecName: Full=Secretin receptor {ECO:0000303|PubMed:1646711};
DE            Short=SCT-R;
DE   Flags: Precursor;
GN   Name=Sctr {ECO:0000312|RGD:621342};
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], AND FUNCTION.
RX   PubMed=1646711; DOI=10.1002/j.1460-2075.1991.tb07686.x;
RA   Ishihara T., Nakamura S., Kaziro Y., Takahashi T., Takahashi K., Nagata S.;
RT   "Molecular cloning and expression of a cDNA encoding the secretin
RT   receptor.";
RL   EMBO J. 10:1635-1641(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Heart;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   SUBCELLULAR LOCATION, GLYCOSYLATION, AND PHOSPHORYLATION.
RX   PubMed=7476911;
RA   Ozcelebi F., Holtmann M.H., Rentsch R.U., Rao R., Miller L.J.;
RT   "Agonist-stimulated phosphorylation of the carboxyl-terminal tail of the
RT   secretin receptor.";
RL   Mol. Pharmacol. 48:818-824(1995).
RN   [4]
RP   FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
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   [5]
RP   FUNCTION, AND MUTAGENESIS OF ARG-36 AND ARG-37.
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   [6]
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   [7]
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).
CC   -!- FUNCTION: Receptor for secretin (SCT), which is involved in different
CC       processes such as regulation of the pH of the duodenal content, food
CC       intake and water homeostasis (PubMed:25332973, PubMed:12403838). The
CC       activity of this receptor is mediated by G proteins which activate
CC       adenylyl cyclase (PubMed:9506976, PubMed:12403838). Upon binding to
CC       secretin, 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). In addition to regulating
CC       the pH of the duodenal content, plays a central role in diet induced
CC       thermogenesis: acts as a non-sympathetic brown fat (BAT) activator
CC       mediating prandial thermogenesis, which consequentially induces
CC       satiation. Mechanistically, secretin released by the gut after a meal
CC       binds to secretin receptor (SCTR) in brown adipocytes, activating brown
CC       fat thermogenesis by stimulating lipolysis, which is sensed in the
CC       brain and promotes satiation. Also able to stimulate lipolysis in white
CC       adipocytes. Also plays an important role in cellular osmoregulation by
CC       regulating renal water reabsorption. Also plays a role in the central
CC       nervous system: required for synaptic plasticity (By similarity).
CC       {ECO:0000250|UniProtKB:P11384, ECO:0000250|UniProtKB:Q5FWI2,
CC       ECO:0000269|PubMed:12403838, ECO:0000269|PubMed:9506976,
CC       ECO:0000303|PubMed:25332973}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:7476911,
CC       ECO:0000269|PubMed:9506976}; Multi-pass membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: In the brain, expressed in the central amygdala,
CC       hippocampus, area postrema, nucleus of the tractus solitary and
CC       cerebellum. {ECO:0000269|PubMed:15276242}.
CC   -!- PTM: Phosphorylated on Ser and Thr residues at the cytoplasmic C-
CC       terminus by G protein-coupled receptor kinases (GRKs).
CC       {ECO:0000269|PubMed:7476911, ECO:0000269|PubMed:9506976}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:7476911}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC       {ECO:0000305}.
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DR   EMBL; X59132; CAA41849.1; -; mRNA.
DR   EMBL; BC081781; AAH81781.1; -; mRNA.
DR   PIR; S16319; S16319.
DR   RefSeq; NP_112377.1; NM_031115.1.
DR   AlphaFoldDB; P23811; -.
DR   SMR; P23811; -.
DR   BioGRID; 249651; 1.
DR   STRING; 10116.ENSRNOP00000064579; -.
DR   GuidetoPHARMACOLOGY; 252; -.
DR   GlyCosmos; P23811; 5 sites, No reported glycans.
DR   GlyGen; P23811; 5 sites.
DR   PhosphoSitePlus; P23811; -.
DR   PaxDb; 10116-ENSRNOP00000064579; -.
DR   Ensembl; ENSRNOT00000119589.1; ENSRNOP00000092013.1; ENSRNOG00000049766.3.
DR   Ensembl; ENSRNOT00055022080; ENSRNOP00055017922; ENSRNOG00055012884.
DR   Ensembl; ENSRNOT00060009352; ENSRNOP00060007027; ENSRNOG00060005612.
DR   Ensembl; ENSRNOT00065015246; ENSRNOP00065011446; ENSRNOG00065009515.
DR   GeneID; 81779; -.
DR   KEGG; rno:81779; -.
DR   AGR; RGD:621342; -.
DR   CTD; 6344; -.
DR   RGD; 621342; Sctr.
DR   eggNOG; KOG4564; Eukaryota.
DR   GeneTree; ENSGT00940000160618; -.
DR   InParanoid; P23811; -.
DR   OrthoDB; 5345963at2759; -.
DR   PhylomeDB; P23811; -.
DR   Reactome; R-RNO-420092; Glucagon-type ligand receptors.
DR   PRO; PR:P23811; -.
DR   Proteomes; UP000002494; Chromosome 13.
DR   GO; GO:0005881; C:cytoplasmic microtubule; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
DR   GO; GO:0042277; F:peptide binding; IDA:RGD.
DR   GO; GO:0017046; F:peptide hormone binding; ISO:RGD.
DR   GO; GO:0015055; F:secretin receptor activity; IDA:RGD.
DR   GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR   GO; GO:0002024; P:diet induced thermogenesis; ISS:UniProtKB.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR   GO; GO:0009992; P:intracellular water homeostasis; ISS:UniProtKB.
DR   GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IDA:RGD.
DR   GO; GO:0050996; P:positive regulation of lipid catabolic process; ISO: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:0070295; P:renal water absorption; ISO:RGD.
DR   GO; GO:0031667; P:response to nutrient levels; ISS:UniProtKB.
DR   CDD; cd15275; 7tmB1_secretin; 1.
DR   Gene3D; 4.10.1240.10; GPCR, family 2, extracellular hormone receptor domain; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR017981; GPCR_2-like_7TM.
DR   InterPro; IPR036445; GPCR_2_extracell_dom_sf.
DR   InterPro; IPR001879; GPCR_2_extracellular_dom.
DR   InterPro; IPR000832; GPCR_2_secretin-like.
DR   InterPro; IPR017983; GPCR_2_secretin-like_CS.
DR   InterPro; IPR002144; GPCR_2_secretin_rcpt.
DR   InterPro; IPR047037; Secretin_7TM.
DR   PANTHER; PTHR45620; PDF RECEPTOR-LIKE PROTEIN-RELATED; 1.
DR   PANTHER; PTHR45620:SF13; SECRETIN RECEPTOR; 1.
DR   Pfam; PF00002; 7tm_2; 1.
DR   Pfam; PF02793; HRM; 1.
DR   PRINTS; PR00249; GPCRSECRETIN.
DR   PRINTS; PR00490; SECRETINR.
DR   SMART; SM00008; HormR; 1.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   SUPFAM; SSF111418; Hormone receptor domain; 1.
DR   PROSITE; PS00649; G_PROTEIN_RECEP_F2_1; 1.
DR   PROSITE; PS00650; G_PROTEIN_RECEP_F2_2; 1.
DR   PROSITE; PS50227; G_PROTEIN_RECEP_F2_3; 1.
DR   PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; G-protein coupled receptor; Glycoprotein; Membrane;
KW   Phosphoprotein; Receptor; Reference proteome; Signal; Transducer;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..449
FT                   /note="Secretin receptor"
FT                   /id="PRO_0000012854"
FT   TOPO_DOM        26..143
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        144..167
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        168..174
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        175..194
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        195..216
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        217..240
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        241..254
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        255..276
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        277..294
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        295..317
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        318..343
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        344..362
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        363..369
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        370..392
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        393..449
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          425..449
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        72
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        100
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        106
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        128
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        291
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         36
FT                   /note="R->A: Strong reduction in secretin (SCT)-binding."
FT                   /evidence="ECO:0000269|PubMed:12403838"
FT   MUTAGEN         37
FT                   /note="R->A: Reduction in secretin (SCT)-binding."
FT                   /evidence="ECO:0000269|PubMed:12403838"
SQ   SEQUENCE   449 AA;  51234 MW;  E70D05B5D061480D CRC64;
     MLSTMRPRLS LLLLRLLLLT KAAHTVGVPP RLCDVRRVLL EERAHCLQQL SKEKKGALGP
     ETASGCEGLW DNMSCWPSSA PARTVEVQCP KFLLMLSNKN GSLFRNCTQD GWSETFPRPD
     LACGVNINNS FNERRHAYLL KLKVMYTVGY SSSLAMLLVA LSILCSFRRL HCTRNYIHMH
     LFVSFILRAL SNFIKDAVLF SSDDVTYCDA HKVGCKLVMI FFQYCIMANY AWLLVEGLYL
     HTLLAISFFS ERKYLQAFVL LGWGSPAIFV ALWAITRHFL ENTGCWDINA NASVWWVIRG
     PVILSILINF IFFINILRIL MRKLRTQETR GSETNHYKRL AKSTLLLIPL FGIHYIVFAF
     SPEDAMEVQL FFELALGSFQ GLVVAVLYCF LNGEVQLEVQ KKWRQWHLQE FPLRPVAFNN
     SFSNATNGPT HSTKASTEQS RSIPRASII
//