CRFR1_SHEEP
ID CRFR1_SHEEP Reviewed; 415 AA.
AC O62772;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 25-MAY-2022, entry version 101.
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;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Pituitary;
RX PubMed=9863624; DOI=10.1016/s0303-7207(98)00157-9;
RA Myers D.A., Trinh J.V., Myers T.R.;
RT "Structure and function of the ovine type 1 corticotropin releasing factor
RT receptor (CRF1) and a carboxyl-terminal variant.";
RL Mol. Cell. Endocrinol. 144:21-35(1998).
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:9863624}.
CC -!- SUBUNIT: Heterodimer; heterodimerizes with GPER1. Interacts (via N-
CC terminal extracellular domain) with CRH and UCN. Interacts with DLG1;
CC this inhibits endocytosis of CRHR1 after agonist binding (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9863624};
CC Multi-pass membrane protein {ECO:0000269|PubMed:9863624}. Endosome
CC {ECO:0000250}. Note=Agonist-binding promotes endocytosis.
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; AF054582; AAC08027.1; -; mRNA.
DR RefSeq; NP_001009727.1; NM_001009727.1.
DR AlphaFoldDB; O62772; -.
DR SMR; O62772; -.
DR GeneID; 443025; -.
DR KEGG; oas:443025; -.
DR CTD; 1394; -.
DR OrthoDB; 1163977at2759; -.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0015056; F:corticotrophin-releasing factor receptor activity; ISS:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
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:2000852; P:regulation of corticosterone secretion; ISS:UniProtKB.
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; 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 2: Evidence at transcript 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_0000012817"
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 51
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; 47559 MW; FA5F652D12B4CDC4 CRC64;
MGRRPQLRLV KALLLLGLNS ISASLQDQHC ESLSLASNVS GLQCNASVDL NGTCWPQSPA
GQLVVRPCLV FFYGVRYNTT SNGYRVCLAN GTWAARVNHS ECQEILSEGE KSKAHYHIAV
IINYLGHCIS LAALLVAFVL FLRLRSIRCV RNIIHWNLIS AFILRNATWF VVQLTMSPEV
HQSNVGWCRL VTAAYNYFHV TNFFWMFGEG CYLHTAVVLT YSTDRLRKWM FICIGWGVPF
PIIVAWAIGK LYYDNEKCWF GKRPGVYTDY IYQGPMILVL LINFIFLFNI VRILMTKLRA
STTSETIQYR KAVKATLVLL PLLGITYMLF FVNPGEDEVS RVVFIYFNSF LESFQGFFVS
VFYCFLNSEV RSAIRKRWHR WQDKHSIRAR VARAMSIPTS PTRVSFHSIK QSTAV
