SCTR_HUMAN
ID SCTR_HUMAN Reviewed; 440 AA.
AC P47872; Q12961; Q13213; Q53T00;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Secretin receptor;
DE Short=SCT-R;
DE Flags: Precursor;
GN Name=SCTR;
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 [MRNA].
RC TISSUE=Pancreas;
RX PubMed=7864894; DOI=10.1006/bbrc.1995.1268;
RA Jiang S., Ulrich C.D.;
RT "Molecular cloning and functional expression of a human pancreatic secretin
RT receptor.";
RL Biochem. Biophys. Res. Commun. 207:883-890(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Pancreas;
RX PubMed=7612008; DOI=10.1006/bbrc.1995.1957;
RA Chow B.K.-C.;
RT "Molecular cloning and functional characterization of a human secretin
RT receptor.";
RL Biochem. Biophys. Res. Commun. 212:204-211(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=7700244;
RA Patel D.R., Kong Y., Sreedharan S.P.;
RT "Molecular cloning and expression of a human secretin receptor.";
RL Mol. Pharmacol. 47:467-473(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S.,
RA Tsutsumi S., Aburatani H., Asai K., Akiyama Y.;
RT "Genome-wide discovery and analysis of human seven transmembrane helix
RT receptor genes.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RA King M.M., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
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:7612008, PubMed:25332973). The
CC activity of this receptor is mediated by G proteins which activate
CC adenylyl cyclase (By similarity). Upon binding to secretin, regulates
CC the pH of the duodenum by (1) inhibiting the secretion of gastric acid
CC from the parietal cells of the stomach and (2) stimulating the
CC production of bicarbonate (NaHCO(3)) from the ductal cells of the
CC pancreas (By similarity). In addition to regulating the pH of the
CC duodenal content, plays a central role in diet induced thermogenesis:
CC acts as a non-sympathetic brown fat (BAT) activator mediating prandial
CC thermogenesis, which consequentially induces satiation.
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. 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:7612008, ECO:0000303|PubMed:25332973}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P23811};
CC Multi-pass membrane protein {ECO:0000255}.
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 -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC {ECO:0000305}.
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DR EMBL; U20178; AAC50106.1; -; mRNA.
DR EMBL; U28281; AAA87556.1; -; mRNA.
DR EMBL; U13989; AAA64949.1; -; mRNA.
DR EMBL; AB065660; BAC05886.1; -; Genomic_DNA.
DR EMBL; AY462218; AAR25625.1; -; mRNA.
DR EMBL; AC013275; AAY14741.1; -; Genomic_DNA.
DR EMBL; CH471103; EAW95219.1; -; Genomic_DNA.
DR CCDS; CCDS2127.1; -.
DR PIR; JC2532; JC2532.
DR RefSeq; NP_002971.2; NM_002980.2.
DR PDB; 6WI9; EM; 4.30 A; R=22-440.
DR PDB; 6WZG; EM; 2.30 A; R=22-440.
DR PDB; 7D3S; EM; 2.90 A; R=23-440.
DR PDBsum; 6WI9; -.
DR PDBsum; 6WZG; -.
DR PDBsum; 7D3S; -.
DR AlphaFoldDB; P47872; -.
DR SMR; P47872; -.
DR BioGRID; 112248; 6.
DR IntAct; P47872; 2.
DR MINT; P47872; -.
DR STRING; 9606.ENSP00000019103; -.
DR BindingDB; P47872; -.
DR ChEMBL; CHEMBL1925; -.
DR DrugBank; DB09532; Secretin human.
DR DrugCentral; P47872; -.
DR GuidetoPHARMACOLOGY; 252; -.
DR TCDB; 9.A.14.4.10; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P47872; 5 sites.
DR iPTMnet; P47872; -.
DR PhosphoSitePlus; P47872; -.
DR BioMuta; SCTR; -.
DR DMDM; 2506489; -.
DR PaxDb; P47872; -.
DR PeptideAtlas; P47872; -.
DR PRIDE; P47872; -.
DR ProteomicsDB; 55806; -.
DR Antibodypedia; 18314; 282 antibodies from 34 providers.
DR DNASU; 6344; -.
DR Ensembl; ENST00000019103.8; ENSP00000019103.6; ENSG00000080293.10.
DR GeneID; 6344; -.
DR KEGG; hsa:6344; -.
DR MANE-Select; ENST00000019103.8; ENSP00000019103.6; NM_002980.3; NP_002971.2.
DR UCSC; uc002tma.4; human.
DR CTD; 6344; -.
DR DisGeNET; 6344; -.
DR GeneCards; SCTR; -.
DR HGNC; HGNC:10608; SCTR.
DR HPA; ENSG00000080293; Group enriched (intestine, pancreas).
DR MIM; 182098; gene.
DR neXtProt; NX_P47872; -.
DR OpenTargets; ENSG00000080293; -.
DR PharmGKB; PA35018; -.
DR VEuPathDB; HostDB:ENSG00000080293; -.
DR eggNOG; KOG4564; Eukaryota.
DR GeneTree; ENSGT00940000160618; -.
DR HOGENOM; CLU_002753_4_4_1; -.
DR InParanoid; P47872; -.
DR OMA; EERDQCL; -.
DR OrthoDB; 651627at2759; -.
DR PhylomeDB; P47872; -.
DR TreeFam; TF315710; -.
DR PathwayCommons; P47872; -.
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; P47872; -.
DR BioGRID-ORCS; 6344; 19 hits in 1075 CRISPR screens.
DR ChiTaRS; SCTR; human.
DR GeneWiki; Secretin_receptor; -.
DR GenomeRNAi; 6344; -.
DR Pharos; P47872; Tclin.
DR PRO; PR:P47872; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P47872; protein.
DR Bgee; ENSG00000080293; Expressed in body of pancreas and 95 other tissues.
DR ExpressionAtlas; P47872; baseline and differential.
DR Genevisible; P47872; HS.
DR GO; GO:0005881; C:cytoplasmic microtubule; IDA: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:0017046; F:peptide hormone binding; IPI:GO_Central.
DR GO; GO:0015055; F:secretin receptor activity; IDA:GO_Central.
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; ISS:UniProtKB.
DR GO; GO:0002024; P:diet induced thermogenesis; ISS:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:GO_Central.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; ISS:UniProtKB.
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 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 3D-structure; Cell membrane; G-protein coupled receptor; Glycoprotein;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Signal; Transducer;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..440
FT /note="Secretin receptor"
FT /id="PRO_0000012852"
FT TOPO_DOM 23..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..440
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
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 VARIANT 110
FT /note="D -> N (in dbSNP:rs6726491)"
FT /id="VAR_049456"
FT VARIANT 122
FT /note="A -> P (in dbSNP:rs3731600)"
FT /id="VAR_033970"
FT CONFLICT 124
FT /note="G -> A (in Ref. 1; AAC50106)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="A -> P (in Ref. 2; AAA87556)"
FT /evidence="ECO:0000305"
FT CONFLICT 308
FT /note="I -> F (in Ref. 3; AAA64949)"
FT /evidence="ECO:0000305"
FT CONFLICT 333
FT /note="E -> Q (in Ref. 3; AAA64949)"
FT /evidence="ECO:0000305"
FT CONFLICT 377
FT /note="G -> A (in Ref. 1; AAC50106)"
FT /evidence="ECO:0000305"
FT HELIX 31..47
FT /evidence="ECO:0007829|PDB:6WZG"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:6WZG"
FT TURN 70..72
FT /evidence="ECO:0007829|PDB:6WZG"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 91..94
FT /evidence="ECO:0007829|PDB:6WZG"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:6WZG"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:6WZG"
FT TURN 117..121
FT /evidence="ECO:0007829|PDB:6WZG"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 133..166
FT /evidence="ECO:0007829|PDB:6WZG"
FT TURN 168..170
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 173..200
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 212..245
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 255..279
FT /evidence="ECO:0007829|PDB:6WZG"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 292..325
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 333..351
FT /evidence="ECO:0007829|PDB:6WZG"
FT TURN 352..354
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 355..358
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 363..365
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 366..374
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 377..379
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 380..388
FT /evidence="ECO:0007829|PDB:6WZG"
FT TURN 389..391
FT /evidence="ECO:0007829|PDB:6WZG"
FT HELIX 393..407
FT /evidence="ECO:0007829|PDB:6WZG"
SQ SEQUENCE 440 AA; 50207 MW; E22CDD0EE7C0ACC1 CRC64;
MRPHLSPPLQ QLLLPVLLAC AAHSTGALPR LCDVLQVLWE EQDQCLQELS REQTGDLGTE
QPVPGCEGMW DNISCWPSSV PGRMVEVECP RFLRMLTSRN GSLFRNCTQD GWSETFPRPN
LACGVNVNDS SNEKRHSYLL KLKVMYTVGY SSSLVMLLVA LGILCAFRRL HCTRNYIHMH
LFVSFILRAL SNFIKDAVLF SSDDVTYCDA HRAGCKLVMV LFQYCIMANY SWLLVEGLYL
HTLLAISFFS ERKYLQGFVA FGWGSPAIFV ALWAIARHFL EDVGCWDINA NASIWWIIRG
PVILSILINF ILFINILRIL MRKLRTQETR GNEVSHYKRL ARSTLLLIPL FGIHYIVFAF
SPEDAMEIQL FFELALGSFQ GLVVAVLYCF LNGEVQLEVQ KKWQQWHLRE FPLHPVASFS
NSTKASHLEQ SQGTCRTSII
