Calcium sensitive receptor
| Calcium sensitive receptor | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 1059 AS ; 118 kDa | |
| Secondary to quaternary structure | multipass membrane protein | |
| Isoforms | 2 | |
| Identifier | ||
| Gene names | CASR ; CAR; FHH; FIH; GPRC2A; HHC; HHC1; MGC138441; NSHPT; PCAR1 | |
| External IDs | ||
| Occurrence | ||
| Homology family | G-protein coupled receptor family 3 | |
| Parent taxon | Euteleostomi | |
The calcium-sensitive receptor ( calcium sensing receptor ) is a receptor protein from the group of G-protein-coupled receptors that is responsible for the cell for determining the extracellular calcium level . The calcium-sensitive receptor occurs particularly on the surface of the main cells of the parathyroid gland and renal tubule cells . It regulates the secretion of the parathyroid hormone parathyroid hormone and the reabsorption of calcium from the primary urine .
Mutations in the gene of the receptor that worsen the function (loss-of-function) lead to familial hypocalzuric hypercalcemia (FHH) and severe neonatal primary hyperparathyroidism . Mutations that increase the activity of the receptor (gain-of-function) can be used for autosomal - dominant hypocalcemia with hypercalciuria lead (decreased serum calcium with increased calcium excretion).
Biosynthesis and protein structure
The gene for the calcium-sensitive receptor CaSR is located on chromosome 3q21 and codes for a membrane-bound protein of 1059 amino acids with a large extracellular domain, seven transmembrane domains and an intracellular appendix. The large extracellular domain consists of two lobes, which are responsible for binding the ligand , and a cysteine- rich portion. After binding of the ligand, dimers are formed on the cell surface and phospholipase C , adenylyl cyclase and protein kinase- dependent intracellular metabolic pathways are activated.
Biological function
In the parathyroid gland, a decrease in extracellular calcium leads to an increase in parathyroid hormone secretion. In the kidneys, an increase in calcium leads to increased calcium excretion.
pathology
In addition to the function-reducing and function-increasing mutations on the receptor, there are other variants.
Gene variants ( polymorphisms ) of the calcium receptor gene can lead to a reduced or increased calcium excretion and thus to a predisposition to develop kidney stones , familial hypocalcuric hypercalcemia or secondary hyperparathyroidism.
Autoantibodies against the calcium-sensitive receptor were found in patients with increased serum calcium (hypercalcemia) and decreased calcium excretion (hypocalciuria), in whom no gene mutation was detectable, and in patients with autoimmune hypoparathyroidism .
pharmacology
Cinacalcet , used in the therapy of secondary hyperparathyroidism , acts as an allosteric modulator and increases the sensitivity of the calcium-sensitive receptor to calcium.
Individual evidence
- ↑ UniProt P41180 .
- ↑ Giuseppe Vezzoli: Influence of Calcium-Sensing Receptor Gene on Urinary Calcium Excretion in Stone-Forming Patients . In: J Am Soc Nephrol . No. 13 , 2002, p. 2517-2523 ( Article Abstract ).
- ↑ Peter H. Nissen et al .: Molecular Genetic Analysis of the Calcium Sensing Receptor Gene in Patients Clinically Suspected to Have Familial Hypocalciuric Hypercalcemia: Phenotypic Variation and Mutation Spectrum in a Danish Population . In: J Clin Endocrinol Metab . No. 92 , 2007, p. 4373-4379 ( abstract ).
- ↑ Calcium-sensitive receptor. In: Online Mendelian Inheritance in Man . (English).