CRFR1_MOUSE
ID CRFR1_MOUSE Reviewed; 415 AA.
AC P35347;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 176.
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 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 [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Pituitary;
RX PubMed=8243652; DOI=10.1016/0014-5793(93)80427-v;
RA Vita N., Laurent P., Lefort S., Chalon P., Lelias J.-M., Kaghad M.,
RA le Fur G., Caput D., Ferrara P.;
RT "Primary structure and functional expression of mouse pituitary and human
RT brain corticotrophin releasing factor receptors.";
RL FEBS Lett. 335:1-5(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ILS, and ISS;
RX PubMed=11471062; DOI=10.1007/s00335-001-1001-x;
RA Ehringer M.A., Thompson J., Conroy O., Xu Y., Yang F., Canniff J.,
RA Beeson M., Gordon L., Bennett B., Johnson T.E., Sikela J.M.;
RT "High-throughput sequence identification of gene coding variants within
RT alcohol-related QTLs.";
RL Mamm. Genome 12:657-663(2001).
RN [3]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9655498; DOI=10.1016/s0896-6273(00)80491-2;
RA Smith G.W., Aubry J.M., Dellu F., Contarino A., Bilezikjian L.M.,
RA Gold L.H., Chen R., Marchuk Y., Hauser C., Bentley C.A., Sawchenko P.E.,
RA Koob G.F., Vale W., Lee K.F.;
RT "Corticotropin releasing factor receptor 1-deficient mice display decreased
RT anxiety, impaired stress response, and aberrant neuroendocrine
RT development.";
RL Neuron 20:1093-1102(1998).
RN [4]
RP INTERACTION WITH DLG1, AND TISSUE SPECIFICITY.
RX PubMed=23576434; DOI=10.1074/jbc.m113.473660;
RA Dunn H.A., Walther C., Godin C.M., Hall R.A., Ferguson S.S.;
RT "Role of SAP97 protein in the regulation of corticotropin-releasing factor
RT receptor 1 endocytosis and extracellular signal-regulated kinase 1/2
RT signaling.";
RL J. Biol. Chem. 288:15023-15034(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:8243652,
CC ECO:0000269|PubMed:9655498}.
CC -!- SUBUNIT: Heterodimer; heterodimerizes with GPER1 (By similarity).
CC Interacts (via N-terminal extracellular domain) with CRH and UCN.
CC Interacts with DLG1; this inhibits endocytosis of CRHR1 after agonist
CC binding. {ECO:0000250, ECO:0000269|PubMed:23576434}.
CC -!- INTERACTION:
CC P35347; P70175: Dlg3; NbExp=3; IntAct=EBI-16879653, EBI-396969;
CC P35347; Q62108: Dlg4; NbExp=7; IntAct=EBI-16879653, EBI-300895;
CC P35347; Q62696: Dlg1; Xeno; NbExp=3; IntAct=EBI-16879653, EBI-389325;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8243652};
CC Multi-pass membrane protein {ECO:0000269|PubMed:8243652}. Endosome
CC {ECO:0000250}. Note=Agonist-binding promotes endocytosis.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in brain cortex (at protein level).
CC {ECO:0000269|PubMed:23576434}.
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 -!- DISRUPTION PHENOTYPE: Heterozygous mice are fertile and produce
CC homozygous pups at the expected Mendelian rate, but about 15% of the
CC homozygous males die between 3 and 12 weeks after birth. Mice are
CC deficient in CRF-mediated secretion of ACTH and show no increase in
CC intracellular cAMP levels in response to CRF. Mice display a marked
CC decrease in the size of the zona fasciculata of the adrenal gland,
CC where corticosterone is produced, and have very low plasma
CC corticosterone levels. Mutant mice display reduced anxiety. They fail
CC to produce increased levels of ACTH and corticosterone in response to
CC stress, contrary to wild type mice. Homozygous mice are fertile, but
CC almost all of the pups die within 48 hours after birth, due to defects
CC in lung inflation and alveolar collapse. Treatment of pregnant females
CC with corticosterone-containing drinking water results in normal lung
CC maturation and normal survival of their progeny.
CC {ECO:0000269|PubMed:9655498}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC {ECO:0000305}.
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DR EMBL; X72305; CAA51053.1; -; mRNA.
DR EMBL; AF483484; AAL90758.1; -; mRNA.
DR EMBL; AF483485; AAL90759.1; -; mRNA.
DR CCDS; CCDS25526.1; -.
DR PIR; S39535; S39535.
DR RefSeq; NP_031788.1; NM_007762.5.
DR AlphaFoldDB; P35347; -.
DR SMR; P35347; -.
DR IntAct; P35347; 6.
DR MINT; P35347; -.
DR STRING; 10090.ENSMUSP00000091455; -.
DR BindingDB; P35347; -.
DR ChEMBL; CHEMBL2446; -.
DR GlyGen; P35347; 5 sites.
DR iPTMnet; P35347; -.
DR PhosphoSitePlus; P35347; -.
DR PaxDb; P35347; -.
DR PRIDE; P35347; -.
DR ProteomicsDB; 284136; -.
DR DNASU; 12921; -.
DR Ensembl; ENSMUST00000093925; ENSMUSP00000091455; ENSMUSG00000018634.
DR GeneID; 12921; -.
DR KEGG; mmu:12921; -.
DR UCSC; uc007lvz.1; mouse.
DR CTD; 1394; -.
DR MGI; MGI:88498; Crhr1.
DR VEuPathDB; HostDB:ENSMUSG00000018634; -.
DR eggNOG; KOG4564; Eukaryota.
DR GeneTree; ENSGT00940000158410; -.
DR HOGENOM; CLU_002753_4_1_1; -.
DR InParanoid; P35347; -.
DR OMA; QEQYCES; -.
DR OrthoDB; 1163977at2759; -.
DR PhylomeDB; P35347; -.
DR TreeFam; TF315710; -.
DR Reactome; R-MMU-373080; Class B/2 (Secretin family receptors).
DR Reactome; R-MMU-418555; G alpha (s) signalling events.
DR BioGRID-ORCS; 12921; 4 hits in 70 CRISPR screens.
DR PHI-base; PHI:4676; -.
DR PRO; PR:P35347; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P35347; protein.
DR Bgee; ENSMUSG00000018634; Expressed in cerebellar cortex and 63 other tissues.
DR ExpressionAtlas; P35347; baseline and differential.
DR Genevisible; P35347; MM.
DR GO; GO:0045177; C:apical part of cell; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005771; C:multivesicular body; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005802; C:trans-Golgi network; ISO:MGI.
DR GO; GO:0031982; C:vesicle; ISO:MGI.
DR GO; GO:0015056; F:corticotrophin-releasing factor receptor activity; IMP:UniProtKB.
DR GO; GO:0051424; F:corticotropin-releasing hormone binding; ISO:MGI.
DR GO; GO:0043404; F:corticotropin-releasing hormone receptor activity; ISO:MGI.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; ISO:MGI.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISO:MGI.
DR GO; GO:0042277; F:peptide binding; ISO:MGI.
DR GO; GO:0017046; F:peptide hormone binding; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0030325; P:adrenal gland development; IMP:UniProtKB.
DR GO; GO:0048148; P:behavioral response to cocaine; ISO:MGI.
DR GO; GO:0048149; P:behavioral response to ethanol; IMP:MGI.
DR GO; GO:0048266; P:behavioral response to pain; ISO:MGI.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0071376; P:cellular response to corticotropin-releasing hormone stimulus; IMP:UniProtKB.
DR GO; GO:0051458; P:corticotropin secretion; IMP:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:MGI.
DR GO; GO:0042596; P:fear response; IMP:UniProtKB.
DR GO; GO:0007631; P:feeding behavior; ISO:MGI.
DR GO; GO:0051867; P:general adaptation syndrome, behavioral process; IMP:MGI.
DR GO; GO:0021854; P:hypothalamus development; IEA:Ensembl.
DR GO; GO:0035641; P:locomotory exploration behavior; ISO:MGI.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISO:MGI.
DR GO; GO:0007613; P:memory; ISO:MGI.
DR GO; GO:0032811; P:negative regulation of epinephrine secretion; ISO:MGI.
DR GO; GO:2000252; P:negative regulation of feeding behavior; ISO:MGI.
DR GO; GO:1901215; P:negative regulation of neuron death; ISO:MGI.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; IEA:Ensembl.
DR GO; GO:0007218; P:neuropeptide signaling pathway; ISO:MGI.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0043306; P:positive regulation of mast cell degranulation; ISO:MGI.
DR GO; GO:0010578; P:regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:2000852; P:regulation of corticosterone secretion; IMP:UniProtKB.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISO:MGI.
DR GO; GO:0051602; P:response to electrical stimulus; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl.
DR GO; GO:0008542; P:visual learning; ISO:MGI.
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 /evidence="ECO:0000255"
FT CHAIN 24..415
FT /note="Corticotropin-releasing factor receptor 1"
FT /id="PRO_0000012815"
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:0000255"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 30..54
FT /evidence="ECO:0000250"
FT DISULFID 44..87
FT /evidence="ECO:0000250"
FT DISULFID 68..102
FT /evidence="ECO:0000250"
FT DISULFID 188..258
FT /evidence="ECO:0000250"
SQ SEQUENCE 415 AA; 47769 MW; 81423BDA6D1CA070 CRC64;
MGQRPQLRLV KALLLLGLNP VSTSLQDQQC ESLSLASNVS GLQCNASVDL IGTCWPRSPA
GQLVVRPCPA FFYGVRYNTT NNGYRECLAN GSWAARVNYS ECQEILNEEK KSKVHYHIAV
IINYLGHCIS LVALLVAFVL FLRLRSIRCL RNIIHWNLIS AFILRNATWF VVQLTVSPEV
HQSNVAWCRL VTAAYNYFHV TNFFWMFGEG CYLHTAIVLT YSTDRLRKWM FVCIGWGVPF
PIIVAWAIGK LYYDNEKCWF GKRPGVYTDY IYQGPMILVL LINFIFLFNI VRILMTKLRA
STTSETIQYR KAVKATLVLL PLLGITYMLF FVNPGEDEVS RVVFIYFNSF LESFQGFFVS
VFYCFLNSEV RSAIRKRWRR WQDKHSIRAR VARAMSIPTS PTRVSFHSIK QSTAV
