The extracellular regions of the homodimer interact in a side-by-side fashion while facing opposite directions (PubMed:27386547, PubMed:27434672). Each extracellular region consists of three domains, LB1 (ligand-binding 1), LB2 and CR (cysteine-rich) (PubMed:17360426). The two lobe-shaped domains LB1 and LB2 form a venus flytrap module (PubMed:27386547, PubMed:27434672). In the inactive configuration, the venus flytrap modules of both protomers are in the open conformation associated with the resting state (open-open) and the interdomain cleft is empty (PubMed:27434672). In addition, each protomer contains three anions, which reinforce the inactive conformation, and one calcium ion (PubMed:27434672). In the active configuration, both protomers of extracellular regions have the closed conformation associated with agonist-binding (closed-closed) (PubMed:27386547, PubMed:27434672). The ligand-binding cleft of each protomer is solely occupied by an aromatic amino-acid (PubMed:27386547, PubMed:27434672). Calcium is bound at four novel sites, including one at the homodimer interface (PubMed:27386547, PubMed:27434672). Agonist-binding induces large conformational changes within the extracellular region homodimer: first, the venus flytrap module of each protomer undergoes domain closure (PubMed:27386547, PubMed:27434672). Second, the LB2 regions of the two protomers approach each other, resulting in an expansion of the homodimer interactions involving LB2 domains (PubMed:27386547, PubMed:27434672). Third, the CR regions of the two subunits interact to form a large homodimer interface that is unique to the active state (PubMed:27386547, PubMed:27434672). The CR regions are brought into close contact by the motion involving LB2 since the two domains are rigidly associated within each subunit (PubMed:27386547, PubMed:27434672).
G-protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis (PubMed:17555508, PubMed:19789209, PubMed:21566075, PubMed:22114145, PubMed:22789683, PubMed:23966241, PubMed:25104082, PubMed:25292184, PubMed:25766501, PubMed:26386835, PubMed:7759551, PubMed:8636323, PubMed:8702647, PubMed:8878438). Senses fluctuations in the circulating calcium concentration and modulates the production of parathyroid hormone (PTH) in parathyroid glands (By similarity). The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system (PubMed:7759551). The G-protein-coupled receptor activity is activated by a co-agonist mechanism: aromatic amino acids, such as Trp or Phe, act concertedly with divalent cations, such as calcium or magnesium, to achieve full receptor activation (PubMed:27386547, PubMed:27434672).
Hypocalciuric hypercalcemia, familial 1
HHC1
A form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. It is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level. Hypermagnesemia is typically present. Affected individuals are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults.
None
The disease is caused by variants affecting the gene represented in this entry.
Hyperparathyroidism, neonatal severe
NSHPT
A disorder characterized by severe hypercalcemia, bone demineralization, and failure to thrive usually manifesting in the first 6 months of life. If untreated, NSHPT can be a devastating neurodevelopmental disorder, which in some cases is lethal without parathyroidectomy.
None
The disease is caused by variants affecting the gene represented in this entry.
Hypocalcemia, autosomal dominant 1
HYPOC1
A disorder of mineral homeostasis characterized by blood calcium levels below normal, and low or normal serum parathyroid hormone concentrations. Disease manifestations include mild or asymptomatic hypocalcemia, paresthesias, carpopedal spasm, seizures, hypercalciuria with nephrocalcinosis or kidney stones, and ectopic and basal ganglia calcifications. Few patients manifest hypocalcemia and features of Bartter syndrome, including hypomagnesemia, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronemia.
None
The disease is caused by variants affecting the gene represented in this entry.
Epilepsy, idiopathic generalized 8
EIG8
A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Seizure types are variable, but include myoclonic seizures, absence seizures, febrile seizures, complex partial seizures, and generalized tonic-clonic seizures.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
N-glycosylated.
Ubiquitinated by RNF19A; which induces proteasomal degradation.
Belongs to the G-protein coupled receptor 3 family.
Expressed in the temporal lobe, frontal lobe, parietal lobe, hippocampus, and cerebellum. Also found in kidney, lung, liver, heart, skeletal muscle, placenta.
GPRC2A, PCAR1, CASR, Extracellular calcium-sensing receptor, CaR, CaSR, hCasR, Parathyroid cell calcium-sensing receptor 1, PCaR1
Proteins
Neuroscience
120675Da
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