ID CRFR1_RAT Reviewed; 415 AA. AC P35353; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 27-MAR-2024, entry version 175. DE RecName: Full=Corticotropin-releasing factor receptor 1; DE Short=CRF-R-1; DE Short=CRF-R1; DE Short=CRFR-1; DE AltName: Full=Corticotropin-releasing hormone receptor 1; DE Short=CRH-R-1; DE Short=CRH-R1; DE Flags: Precursor; GN Name=Crhr1; Synonyms=Crhr; 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], FUNCTION, AND SUBCELLULAR LOCATION. RC STRAIN=Sprague-Dawley; TISSUE=Brain; RX PubMed=8243338; DOI=10.1210/endo.133.6.8243338; RA Perrin M.H., Donaldson C.J., Chen R., Lewis K.A., Vale W.W.; RT "Cloning and functional expression of a rat brain corticotropin releasing RT factor (CRF) receptor."; RL Endocrinology 133:3058-3061(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC STRAIN=Sprague-Dawley; TISSUE=Cerebellum; RX PubMed=8274282; DOI=10.1016/0896-6273(93)90230-o; RA Chang C.P., Pearse R.V. II, O'Connell S., Rosenfeld M.G.; RT "Identification of a seven transmembrane helix receptor for corticotropin- RT releasing factor and sauvagine in mammalian brain."; RL Neuron 11:1187-1195(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Testis; RX PubMed=8662941; DOI=10.1074/jbc.271.24.14519; RA Tsai-Morris C.-H., Buczko E., Geng Y., Gamboa-Pinto A., Dufau M.L.; RT "The genomic structure of the rat corticotropin releasing factor receptor. RT A member of the class II G protein-coupled receptors."; RL J. Biol. Chem. 271:14519-14525(1996). RN [4] RP FUNCTION, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-38; ASN-45; ASN-78; RP ASN-90 AND ASN-98. RX PubMed=11567096; DOI=10.1110/ps.12101; RA Hofmann B.A., Sydow S., Jahn O., van Werven L., Liepold T., Eckart K., RA Spiess J.; RT "Functional and protein chemical characterization of the N-terminal domain RT of the rat corticotropin-releasing factor receptor 1."; RL Protein Sci. 10:2050-2062(2001). RN [5] RP SUBUNIT. RX PubMed=23300088; DOI=10.1074/jbc.m112.412478; RA Akama K.T., Thompson L.I., Milner T.A., McEwen B.S.; RT "Post-synaptic density-95 (PSD-95) binding capacity of G-protein-coupled RT receptor 30 (GPR30), an estrogen receptor that can be identified in RT hippocampal dendritic spines."; RL J. Biol. Chem. 288:6438-6450(2013). CC -!- FUNCTION: G-protein coupled receptor for CRH (corticotropin-releasing CC factor) and UCN (urocortin). Has high affinity for CRH and UCN. Ligand CC binding causes a conformation change that triggers signaling via CC guanine nucleotide-binding proteins (G proteins) and down-stream CC effectors, such as adenylate cyclase. Promotes the activation of CC adenylate cyclase, leading to increased intracellular cAMP levels. CC Inhibits the activity of the calcium channel CACNA1H. Required for CC normal embryonic development of the adrenal gland and for normal CC hormonal responses to stress. Plays a role in the response to CC anxiogenic stimuli. {ECO:0000269|PubMed:11567096, CC ECO:0000269|PubMed:8243338, ECO:0000269|PubMed:8274282}. CC -!- SUBUNIT: Interacts (via N-terminal extracellular domain) with CRH and CC UCN. Interacts with DLG1; this inhibits endocytosis of CRHR1 after CC agonist binding (By similarity). Heterodimer; heterodimerizes with CC GPER1. {ECO:0000250, ECO:0000269|PubMed:23300088}. CC -!- INTERACTION: CC P35353; P55090: Ucn; NbExp=3; IntAct=EBI-9030306, EBI-9030248; CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. CC Endosome {ECO:0000250}. Note=Agonist-binding promotes endocytosis. CC {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Detected in brain, especially in cerebellum. CC Detected in pituitary gland, and at lower levels in the olfactory bulb. CC {ECO:0000269|PubMed:8274282}. CC -!- DOMAIN: The transmembrane domain is composed of seven transmembrane CC helices that are arranged in V-shape. Transmembrane helix 7 assumes a CC sharply kinked structure (By similarity). {ECO:0000250}. CC -!- PTM: C-terminal Ser or Thr residues may be phosphorylated. CC -!- PTM: Phosphorylation at Ser-301 by PKA prevents maximal coupling to Gq- CC protein, and thereby negatively regulates downstream signaling. CC {ECO:0000250}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L24096; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; L25438; AAA16441.1; -; mRNA. DR EMBL; U53498; AAC53519.1; -; Genomic_DNA. DR EMBL; U53486; AAC53519.1; JOINED; Genomic_DNA. DR EMBL; U53487; AAC53519.1; JOINED; Genomic_DNA. DR EMBL; U53488; AAC53519.1; JOINED; Genomic_DNA. DR EMBL; U53489; AAC53519.1; JOINED; Genomic_DNA. DR EMBL; U53490; AAC53519.1; JOINED; Genomic_DNA. DR EMBL; U53491; AAC53519.1; JOINED; Genomic_DNA. DR EMBL; U53492; AAC53519.1; JOINED; Genomic_DNA. DR EMBL; U53493; AAC53519.1; JOINED; Genomic_DNA. DR EMBL; U53494; AAC53519.1; JOINED; Genomic_DNA. DR EMBL; U53495; AAC53519.1; JOINED; Genomic_DNA. DR EMBL; U53496; AAC53519.1; JOINED; Genomic_DNA. DR EMBL; U53497; AAC53519.1; JOINED; Genomic_DNA. DR PIR; I58144; I58144. DR RefSeq; NP_112261.1; NM_030999.4. DR AlphaFoldDB; P35353; -. DR SMR; P35353; -. DR BioGRID; 248692; 4. DR IntAct; P35353; 1. DR STRING; 10116.ENSRNOP00000006764; -. DR BindingDB; P35353; -. DR ChEMBL; CHEMBL4649; -. DR GuidetoPHARMACOLOGY; 212; -. DR GlyCosmos; P35353; 5 sites, No reported glycans. DR GlyGen; P35353; 5 sites. DR iPTMnet; P35353; -. DR PhosphoSitePlus; P35353; -. DR PaxDb; 10116-ENSRNOP00000006764; -. DR Ensembl; ENSRNOT00055049662; ENSRNOP00055040862; ENSRNOG00055028694. DR Ensembl; ENSRNOT00060025266; ENSRNOP00060020129; ENSRNOG00060014769. DR Ensembl; ENSRNOT00065054188; ENSRNOP00065044592; ENSRNOG00065031411. DR GeneID; 58959; -. DR KEGG; rno:58959; -. DR AGR; RGD:61276; -. DR CTD; 1394; -. DR RGD; 61276; Crhr1. DR VEuPathDB; HostDB:ENSRNOG00000004900; -. DR eggNOG; KOG4564; Eukaryota. DR HOGENOM; CLU_002753_4_1_1; -. DR InParanoid; P35353; -. DR OrthoDB; 5345963at2759; -. DR PhylomeDB; P35353; -. DR TreeFam; TF315710; -. DR Reactome; R-RNO-373080; Class B/2 (Secretin family receptors). DR PRO; PR:P35353; -. DR Proteomes; UP000002494; Chromosome 10. DR Bgee; ENSRNOG00000004900; Expressed in cerebellum and 3 other cell types or tissues. DR ExpressionAtlas; P35353; baseline and differential. DR GO; GO:0045177; C:apical part of cell; IDA:RGD. DR GO; GO:0030425; C:dendrite; IDA:RGD. DR GO; GO:0016020; C:membrane; ISO:RGD. DR GO; GO:0005771; C:multivesicular body; IDA:RGD. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0005802; C:trans-Golgi network; IDA:RGD. DR GO; GO:0031982; C:vesicle; IDA:RGD. DR GO; GO:0015056; F:corticotrophin-releasing factor receptor activity; ISS:UniProtKB. DR GO; GO:0051424; F:corticotropin-releasing hormone binding; IDA:RGD. DR GO; GO:0043404; F:corticotropin-releasing hormone receptor activity; IDA:RGD. DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central. DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:RGD. DR GO; GO:0001965; F:G-protein alpha-subunit binding; IPI:RGD. DR GO; GO:0042277; F:peptide binding; IDA:RGD. DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:RGD. DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IDA:RGD. DR GO; GO:0030325; P:adrenal gland development; ISO:RGD. DR GO; GO:0048148; P:behavioral response to cocaine; IMP:RGD. DR GO; GO:0048149; P:behavioral response to ethanol; ISO:RGD. DR GO; GO:0048266; P:behavioral response to pain; IMP:RGD. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro. DR GO; GO:0071376; P:cellular response to corticotropin-releasing hormone stimulus; ISS:UniProtKB. DR GO; GO:0051458; P:corticotropin secretion; ISS:UniProtKB. DR GO; GO:0030855; P:epithelial cell differentiation; IMP:RGD. DR GO; GO:0035640; P:exploration behavior; ISO:RGD. DR GO; GO:0042596; P:fear response; ISO:RGD. DR GO; GO:0007631; P:feeding behavior; IMP:RGD. DR GO; GO:0051867; P:general adaptation syndrome, behavioral process; ISO:RGD. DR GO; GO:0021854; P:hypothalamus development; IEP:RGD. DR GO; GO:0035641; P:locomotory exploration behavior; IMP:RGD. DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:RGD. DR GO; GO:0007613; P:memory; IMP:RGD. DR GO; GO:0032811; P:negative regulation of epinephrine secretion; IMP:RGD. DR GO; GO:2000252; P:negative regulation of feeding behavior; IMP:RGD. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD. DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:RGD. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IDA:RGD. DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IMP:RGD. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:RGD. DR GO; GO:0043306; P:positive regulation of mast cell degranulation; IMP:RGD. DR GO; GO:2000852; P:regulation of corticosterone secretion; ISS:UniProtKB. DR GO; GO:0048167; P:regulation of synaptic plasticity; IMP:RGD. DR GO; GO:0051602; P:response to electrical stimulus; IMP:RGD. DR GO; GO:0001666; P:response to hypoxia; IMP:RGD. DR GO; GO:0035902; P:response to immobilization stress; IEP:RGD. DR GO; GO:0008542; P:visual learning; IMP:RGD. DR CDD; cd15445; 7tmB1_CRF-R1; 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; IPR003052; GPCR_2_CRF1_rcpt. DR InterPro; IPR003051; GPCR_2_CRF_rcpt. 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 PANTHER; PTHR45620:SF2; CORTICOTROPIN-RELEASING FACTOR RECEPTOR 1; 1. DR PANTHER; PTHR45620; PDF RECEPTOR-LIKE PROTEIN-RELATED; 1. DR Pfam; PF00002; 7tm_2; 1. DR Pfam; PF02793; HRM; 1. DR PRINTS; PR01279; CRFRECEPTOR. DR PRINTS; PR01280; CRFRECEPTOR1. DR PRINTS; PR00249; GPCRSECRETIN. 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. DR Genevisible; P35353; RN. PE 1: Evidence at protein level; KW Cell membrane; Disulfide bond; Endosome; G-protein coupled receptor; KW Glycoprotein; Membrane; Phosphoprotein; Receptor; Reference proteome; KW Signal; Transducer; Transmembrane; Transmembrane helix. FT SIGNAL 1..23 FT CHAIN 24..415 FT /note="Corticotropin-releasing factor receptor 1" FT /id="PRO_0000012816" FT TOPO_DOM 24..111 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 112..142 FT /note="Helical; Name=1" FT /evidence="ECO:0000250" FT TOPO_DOM 143..149 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 150..174 FT /note="Helical; Name=2" FT /evidence="ECO:0000250" FT TOPO_DOM 175..189 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 190..218 FT /note="Helical; Name=3" FT /evidence="ECO:0000250" FT TOPO_DOM 219..225 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 226..253 FT /note="Helical; Name=4" FT /evidence="ECO:0000250" FT TOPO_DOM 254..269 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 270..295 FT /note="Helical; Name=5" FT /evidence="ECO:0000250" FT TOPO_DOM 296..306 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 307..331 FT /note="Helical; Name=6" FT /evidence="ECO:0000250" FT TOPO_DOM 332..338 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 339..368 FT /note="Helical; Name=7" FT /evidence="ECO:0000250" FT TOPO_DOM 369..415 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT REGION 99..108 FT /note="Important for peptide agonist binding" FT /evidence="ECO:0000250" FT REGION 280..290 FT /note="Important for antagonist binding" FT /evidence="ECO:0000250" FT MOD_RES 301 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000250|UniProtKB:P34998" FT CARBOHYD 38 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:11567096" FT CARBOHYD 45 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:11567096" FT CARBOHYD 78 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:11567096" FT CARBOHYD 90 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:11567096" FT CARBOHYD 98 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:11567096" FT DISULFID 30..54 FT /evidence="ECO:0000269|PubMed:11567096" FT DISULFID 44..87 FT /evidence="ECO:0000269|PubMed:11567096" FT DISULFID 68..102 FT /evidence="ECO:0000269|PubMed:11567096" FT DISULFID 188..258 FT /evidence="ECO:0000250" SQ SEQUENCE 415 AA; 47842 MW; 48D6704B31D4C013 CRC64; MGRRPQLRLV KALLLLGLNP VSTSLQDQRC ENLSLTSNVS GLQCNASVDL IGTCWPRSPA GQLVVRPCPA FFYGVRYNTT NNGYRECLAN GSWAARVNYS ECQEILNEEK KSKVHYHVAV IINYLGHCIS LVALLVAFVL FLRLRSIRCL RNIIHWNLIS AFILRNATWF VVQLTVSPEV HQSNVAWCRL VTAAYNYFHV TNFFWMFGEG CYLHTAIVLT YSTDRLRKWM FVCIGWGVPF PIIVAWAIGK LHYDNEKCWF GKRPGVYTDY IYQGPMILVL LINFIFLFNI VRILMTKLRA STTSETIQYR KAVKATLVLL PLLGITYMLF FVNPGEDEVS RVVFIYFNSF LESFQGFFVS VFYCFLNSEV RSAIRKRWRR WQDKHSIRAR VARAMSIPTS PTRVSFHSIK QSTAV //