UniProt functional annotation for P34998



	UniProt functional annotation for P34998

UniProt code: P34998.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:18292205, ECO:0000269|PubMed:18801728, ECO:0000269|PubMed:23576434, ECO:0000269|PubMed:23863939}.

Subunit: Heterodimer; heterodimerizes with GPER1 (By similarity). Interacts (via N-terminal extracellular domain) with CRH and UCN. Interacts with DLG1; this inhibits endocytosis of CRHR1 after agonist binding. {ECO:0000250, ECO:0000269|PubMed:18801728, ECO:0000269|PubMed:20843795, ECO:0000269|PubMed:20966082, ECO:0000269|PubMed:23576434, ECO:0000269|PubMed:23863939}.

Subcellular location: Cell membrane; Multi-pass membrane protein. Endosome. Note=Agonist-binding promotes endocytosis.

Tissue specificity: Predominantly expressed in the cerebellum, pituitary, cerebral cortex and olfactory lobe. {ECO:0000269|PubMed:8243652}.

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.

Ptm: C-terminal Ser or Thr residues may be phosphorylated. {ECO:0000269|PubMed:14657255}.

Ptm: Phosphorylation at Ser-330 by PKA prevents maximal coupling to Gq- protein, and thereby negatively regulates downstream signaling. {ECO:0000269|PubMed:14657255}.

Miscellaneous: [Isoform CRF-R2]: Major isoform. {ECO:0000305}.

Miscellaneous: [Isoform CRF-R3]: Does not bind to CRF with high affinity. {ECO:0000305}.

Similarity: Belongs to the G-protein coupled receptor 2 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:18292205, ECO:0000269\|PubMed:18801728, ECO:0000269\|PubMed:23576434, ECO:0000269\|PubMed:23863939}.


Subunit:		Heterodimer; heterodimerizes with GPER1 (By similarity). Interacts (via N-terminal extracellular domain) with CRH and UCN. Interacts with DLG1; this inhibits endocytosis of CRHR1 after agonist binding. {ECO:0000250, ECO:0000269\|PubMed:18801728, ECO:0000269\|PubMed:20843795, ECO:0000269\|PubMed:20966082, ECO:0000269\|PubMed:23576434, ECO:0000269\|PubMed:23863939}.
Subcellular location:		Cell membrane; Multi-pass membrane protein. Endosome. Note=Agonist-binding promotes endocytosis.
Tissue specificity:		Predominantly expressed in the cerebellum, pituitary, cerebral cortex and olfactory lobe. {ECO:0000269\|PubMed:8243652}.
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.
Ptm:		C-terminal Ser or Thr residues may be phosphorylated. {ECO:0000269\|PubMed:14657255}.
Ptm:		Phosphorylation at Ser-330 by PKA prevents maximal coupling to Gq- protein, and thereby negatively regulates downstream signaling. {ECO:0000269\|PubMed:14657255}.
Miscellaneous:		[Isoform CRF-R2]: Major isoform. {ECO:0000305}.
Miscellaneous:		[Isoform CRF-R3]: Does not bind to CRF with high affinity. {ECO:0000305}.
Similarity:		Belongs to the G-protein coupled receptor 2 family. {ECO:0000305}.