CRHR1
Domain
The transmembrane domain is composed of seven transmembrane helices that are arranged in V-shape. Transmembrane helix 7 assumes a sharply kinked structure. The antagonist CP-376395 binds at an allosteric site, far from the presumed binding site for the physiological peptide ligand.
Function
G-protein coupled receptor for CRH (corticotropin-releasing factor) and UCN (urocortin). Has high affinity for CRH and UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels. Inhibits the activity of the calcium channel CACNA1H. Required for normal embryonic development of the adrenal gland and for normal hormonal responses to stress. Plays a role in the response to anxiogenic stimuli.
Post-translational modifications
C-terminal Ser or Thr residues may be phosphorylated.
Phosphorylation at Ser-301 by PKA prevents maximal coupling to Gq-protein, and thereby negatively regulates downstream signaling.
Sequence Similarities
Belongs to the G-protein coupled receptor 2 family.
Tissue Specificity
Predominantly expressed in the cerebellum, pituitary, cerebral cortex and olfactory lobe.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Endosome
- Agonist-binding promotes endocytosis.
Alternative names
CRFR, CRFR1, CRHR, CRHR1, Corticotropin-releasing factor receptor 1, CRF-R-1, CRF-R1, CRFR-1, Corticotropin-releasing hormone receptor 1, CRH-R-1, CRH-R1