CRFR1_RAT
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 03-AUG-2022, entry version 167.
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}.
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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 GlyGen; P35353; 5 sites.
DR iPTMnet; P35353; -.
DR PhosphoSitePlus; P35353; -.
DR PaxDb; P35353; -.
DR GeneID; 58959; -.
DR KEGG; rno:58959; -.
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 OMA; QEQYCES; -.
DR OrthoDB; 1163977at2759; -.
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 tissues.
DR ExpressionAtlas; P35353; baseline and differential.
DR Genevisible; P35353; RN.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA: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; IDA:RGD.
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:0017046; F:peptide hormone binding; IBA:GO_Central.
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: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:1901215; P:negative regulation of neuron death; IMP:RGD.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; ISO: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:0010578; P:regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway; ISO: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 Gene3D; 4.10.1240.10; -; 1.
DR InterPro; IPR017981; GPCR_2-like.
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 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; 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; 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
