SCTR_RAT
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 03-AUG-2022, entry version 122.
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 GlyGen; P23811; 5 sites.
DR PhosphoSitePlus; P23811; -.
DR PaxDb; P23811; -.
DR Ensembl; ENSRNOT00000119589; ENSRNOP00000092013; ENSRNOG00000049766.
DR GeneID; 81779; -.
DR KEGG; rno:81779; -.
DR CTD; 6344; -.
DR RGD; 621342; Sctr.
DR eggNOG; KOG4564; Eukaryota.
DR GeneTree; ENSGT00940000160618; -.
DR InParanoid; P23811; -.
DR OrthoDB; 651627at2759; -.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0007420; P:brain development; IEP:RGD.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0009992; P:cellular water homeostasis; ISS:UniProtKB.
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: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 Gene3D; 4.10.1240.10; -; 1.
DR InterPro; IPR017981; GPCR_2-like.
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 PANTHER; PTHR45620:SF13; PTHR45620:SF13; 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; SSF111418; SSF111418; 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
