SCTR_MOUSE
ID SCTR_MOUSE Reviewed; 447 AA.
AC Q5FWI2; Q80T66;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Secretin receptor {ECO:0000303|PubMed:30449620};
DE Short=SCT-R;
DE Flags: Precursor;
GN Name=Sctr {ECO:0000303|PubMed:30449620, ECO:0000312|MGI:MGI:2441720};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 264-360.
RX PubMed=12679517; DOI=10.1073/pnas.0230374100;
RA Vassilatis D.K., Hohmann J.G., Zeng H., Li F., Ranchalis J.E.,
RA Mortrud M.T., Brown A., Rodriguez S.S., Weller J.R., Wright A.C.,
RA Bergmann J.E., Gaitanaris G.A.;
RT "The G protein-coupled receptor repertoires of human and mouse.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:4903-4908(2003).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=17008357; DOI=10.1093/hmg/ddl402;
RA Nishijima I., Yamagata T., Spencer C.M., Weeber E.J., Alekseyenko O.,
RA Sweatt J.D., Momoi M.Y., Ito M., Armstrong D.L., Nelson D.L., Paylor R.,
RA Bradley A.;
RT "Secretin receptor-deficient mice exhibit impaired synaptic plasticity and
RT social behavior.";
RL Hum. Mol. Genet. 15:3241-3250(2006).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17283064; DOI=10.1128/mcb.01088-06;
RA Chu J.Y., Chung S.C., Lam A.K., Tam S., Chung S.K., Chow B.K.;
RT "Phenotypes developed in secretin receptor-null mice indicated a role for
RT secretin in regulating renal water reabsorption.";
RL Mol. Cell. Biol. 27:2499-2511(2007).
RN [5]
RP FUNCTION.
RX PubMed=20927047; DOI=10.1038/npp.2010.178;
RA Cheng C.Y., Chu J.Y., Chow B.K.;
RT "Central and peripheral administration of secretin inhibits food intake in
RT mice through the activation of the melanocortin system.";
RL Neuropsychopharmacology 36:459-471(2011).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24769669; DOI=10.1096/fj.13-247536;
RA Sekar R., Chow B.K.;
RT "Secretin receptor-knockout mice are resistant to high-fat diet-induced
RT obesity and exhibit impaired intestinal lipid absorption.";
RL FASEB J. 28:3494-3505(2014).
RN [7]
RP FUNCTION.
RX PubMed=24273196; DOI=10.1194/jlr.m038042;
RA Sekar R., Chow B.K.;
RT "Lipolytic actions of secretin in mouse adipocytes.";
RL J. Lipid Res. 55:190-200(2014).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
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: 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:20927047, PubMed:24273196,
CC PubMed:30449620). The activity of this receptor is mediated by G
CC proteins which activate adenylyl cyclase (PubMed:30449620). Upon
CC binding to secretin, regulates the pH of the duodenum by (1) inhibiting
CC the secretion of gastric acid from the parietal cells of the stomach
CC and (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 (PubMed:30449620). 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 (PubMed:30449620). Also able
CC to stimulate lipolysis in white adipocytes (PubMed:24273196). Also
CC plays an important role in cellular osmoregulation by regulating renal
CC water reabsorption (PubMed:17283064). Also plays a role in the central
CC nervous system: required for synaptic plasticity (PubMed:17008357).
CC {ECO:0000250|UniProtKB:P11384, ECO:0000269|PubMed:17008357,
CC ECO:0000269|PubMed:17283064, ECO:0000269|PubMed:20927047,
CC ECO:0000269|PubMed:24273196, ECO:0000269|PubMed:30449620}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P23811};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: In brain, expressed in the hippocampal CA1 region,
CC the lower layer of cerebral cortex, the anterior olfactory nuclei, the
CC anterior ventrolateral thalamus, the lateral region of hypothalamus,
CC substantia nigra, tegmental area and central nucleus of the inferior
CC colliculus, the ventral supramamillary nucleus and the cerebellum
CC (PubMed:17008357). Expressed in brown adipocytes: expression
CC predominates in mature brown adipocytes (at protein level)
CC (PubMed:30449620). {ECO:0000269|PubMed:17008357,
CC ECO:0000269|PubMed:30449620}.
CC -!- PTM: Phosphorylated on Ser and Thr residues at the cytoplasmic C-
CC terminus by G protein-coupled receptor kinases (GRKs).
CC {ECO:0000250|UniProtKB:P23811}.
CC -!- DISRUPTION PHENOTYPE: Mice are overtly normal and fertile
CC (PubMed:17008357). Mice however display impaired synaptic plasticity in
CC the hippocampus: the number of dendritic spines in the CA1 hippocampal
CC pyramidal cells is slightly reduced and mice show abnormal social
CC behavior (PubMed:17008357). Mice are not hyperphagic and display normal
CC food intake (PubMed:24769669). Following a 12 week high-fat diet,
CC knockout mice gain significantly less weight and exhibit lower body fat
CC content, possibly caused by reduced fat absorption in the intestine
CC (PubMed:24769669). Mice also show mild polydipsia and polyuria; kidney
CC display altered glomerular and tubular morphology (PubMed:17283064).
CC {ECO:0000269|PubMed:17008357, ECO:0000269|PubMed:17283064,
CC ECO:0000269|PubMed:24769669}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC {ECO:0000305}.
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DR EMBL; BC089355; AAH89355.1; -; mRNA.
DR EMBL; AY255623; AAO85135.1; -; mRNA.
DR CCDS; CCDS78668.1; -.
DR RefSeq; NP_001012322.2; NM_001012322.2.
DR RefSeq; NP_001298006.1; NM_001311077.1.
DR AlphaFoldDB; Q5FWI2; -.
DR SMR; Q5FWI2; -.
DR STRING; 10090.ENSMUSP00000072660; -.
DR GlyGen; Q5FWI2; 5 sites.
DR PaxDb; Q5FWI2; -.
DR PRIDE; Q5FWI2; -.
DR Antibodypedia; 18314; 282 antibodies from 34 providers.
DR DNASU; 319229; -.
DR Ensembl; ENSMUST00000189037; ENSMUSP00000139932; ENSMUSG00000026387.
DR GeneID; 319229; -.
DR KEGG; mmu:319229; -.
DR UCSC; uc007cjc.1; mouse.
DR CTD; 6344; -.
DR MGI; MGI:2441720; Sctr.
DR VEuPathDB; HostDB:ENSMUSG00000026387; -.
DR eggNOG; KOG4564; Eukaryota.
DR GeneTree; ENSGT00940000160618; -.
DR InParanoid; Q5FWI2; -.
DR OrthoDB; 651627at2759; -.
DR PhylomeDB; Q5FWI2; -.
DR Reactome; R-MMU-418555; G alpha (s) signalling events.
DR Reactome; R-MMU-420092; Glucagon-type ligand receptors.
DR BioGRID-ORCS; 319229; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q5FWI2; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q5FWI2; protein.
DR Bgee; ENSMUSG00000026387; Expressed in hindlimb stylopod muscle and 47 other tissues.
DR ExpressionAtlas; Q5FWI2; baseline and differential.
DR Genevisible; Q5FWI2; MM.
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; ISO:MGI.
DR GO; GO:0017046; F:peptide hormone binding; ISO:MGI.
DR GO; GO:0015055; F:secretin receptor activity; IDA:UniProtKB.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IBA:GO_Central.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0009992; P:cellular water homeostasis; IMP:UniProtKB.
DR GO; GO:0002024; P:diet induced thermogenesis; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0050996; P:positive regulation of lipid catabolic process; IDA:UniProtKB.
DR GO; GO:0032098; P:regulation of appetite; IDA:UniProtKB.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IMP:UniProtKB.
DR GO; GO:0070295; P:renal water absorption; IMP:UniProtKB.
DR GO; GO:0031667; P:response to nutrient levels; IDA: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; 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..28
FT /evidence="ECO:0000255"
FT CHAIN 29..447
FT /note="Secretin receptor"
FT /id="PRO_0000043222"
FT TOPO_DOM 29..142
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..166
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 167..173
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..193
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..215
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 216..239
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 240..253
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 254..275
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 276..293
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 294..316
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 317..342
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 343..361
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 362..368
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 369..391
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 392..447
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 423..447
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 447 AA; 50932 MW; DD937AFC33D41115 CRC64;
MLSTMSPRLS LLLLWLLLLI NAAHPVGALP RLCDVRRVLL EERAECLREL SEEKKALGPK
TASGCERFWD NMSCWPSSAL AQTVEVPCPK FLRMFSGRNG SLFRNCTKDG WSETFPRPDL
ACGVNMNGSF NERRHAYLLK LKVMYTVGYS SSLAMLLVAL SILCSFRRLH CTRNYIHMHL
FVSFILRALS NFIKDAVLFP ADDVTYCDAH RAGCKLVMIF FQYCIMANYA WLLVEGLYLH
TLLAISFFSE RKCLQAFVLF GWGSPAIFVA LWAVTRHFLE DFGCWDINSN ASIWWVIRGP
VILSIVINFI FFINILRILM RKLRTQETRG NETHHYKRLA KSTLLLIPLF GIHYIVFAFS
PEGAMEVQLF FELALGSFQG LVVAVLYCFL NGELEVQKKW RQWHLQEFPL RPVALSNSFS
NATNGPTHST KAGTSEQSRS IPGANVI
