CASR Membrane Protein Introduction

Introduction of CASR

CASR is encoded by the CASR gene. CASR is a widely distributed G protein-coupled receptor. The human CASR gene is located on the long arm of chromosome 3 and consists of 1,078 amino acids and can be divided into three independent domains. The extracellular domain can form a dimer and then combine with polyvalent cations (Ca²⁺, Gd³⁺, and Mg²⁺), spermine, polyamines, multivalent antibiotics, and aromatic L-type amino acids to activate CASR and initiate downstream signal pathways that regulate cell function.

Basic Information of CASR
Protein Name	Extracellular calcium-sensing receptor
Gene Name	CASR
Aliases	CAR, EIG8, FHH, FIH, GPRC2A, HHC, HHC1, HYPOC1, NSHPT, PCAR1, calcium sensing receptor, hCasR, Calcium-sensing receptor+CaSR
Organism	Homo sapiens (Human)
UniProt ID	P41180
Transmembrane Times	7
Length (aa)	1078
Sequence	MAFYSCCWVLLALTWHTSAYGPDQRAQKKGDIILGGLFPIHFGVAAKDQDLKSRPESVECIR YNFRGFRWLQAMIFAIEEINSSPALLPNLTLGYRIFDTCNTVSKALEATLSFVAQNKIDSLN LDEFCNCSEHIPSTIAVVGATGSGVSTAVANLLGLFYIPQVSYASSSRLLSNKNQFKSFLRT IPNDEHQATAMADIIEYFRWNWVGTIAADDDYGRPGIEKFREEAEERDICIDFSELISQYSD EEEIQHVVEVIQNSTAKVIVVFSSGPDLEPLIKEIVRRNITGKIWLASEAWASSSLIAMPQY FHVVGGTIGFALKAGQIPGFREFLKKVHPRKSVHNGFAKEFWEETFNCHLQEGAKGPLPVDT FLRGHEESGDRFSNSSTAFRPLCTGDENISSVETPYIDYTHLRISYNVYLAVYSIAHALQDI YTCLPGRGLFTNGSCADIKKVEAWQVLKHLRHLNFTNNMGEQVTFDECGDLVGNYSIINWHL SPEDGSIVFKEVGYYNVYAKKGERLFINEEKILWSGFSREVPFSNCSRDCLAGTRKGIIEGE PTCCFECVECPDGEYSDETDASACNKCPDDFWSNENHTSCIAKEIEFLSWTEPFGIALTLFA VLGIFLTAFVLGVFIKFRNTPIVKATNRELSYLLLFSLLCCFSSSLFFIGEPQDWTCRLRQP AFGISFVLCISCILVKTNRVLLVFEAKIPTSFHRKWWGLNLQFLLVFLCTFMQIVICVIWLY TAPPSSYRNQELEDEIIFITCHEGSLMALGFLIGYTCLLAAICFFFAFKSRKLPENFNEAKF ITFSMLIFFIVWISFIPAYASTYGKFVSAVEVIAILAASFGLLACIFFNKIYIILFKPSRNT IEEVRCSTAAHAFKVAARATLRRSNVSRKRSSSLGGSTGSTPSSSISSKSNSEDPFPQPERQ KQQQPLALTQQEQQQQPLTLPQQQRSQQQPRCKQKVIFGSGTVTFSLSFDEPQKNAMAHRNS THQNSLEAQKSSDTLTRHEPLLPLQCGETDLDLTVQETGLQGPVGGDQRPEVEDPEELSPAL VVSSSQSFVISGGGSTVTENVVNS

Function of CASR Membrane Protein

CASR binds to extracellular Ca²⁺, CASR agonists, and allosteric modulators to activate itself, thereby directly activating G protein-coupled downstream signaling pathways. Its classical signal transduction pathway is mainly through the activation of CASR to hydrolyze phospholipase C (PLC) and phosphatidylinositol-4,5-bisphosphate, (PIP2), and release inositol-1, 4,5-triphosphate (IP3) and diacylglycerol (DAG). IP3 can bind to specific receptors on the surface of the endoplasmic reticulum and release a large amount of intracellular Ca²⁺. In addition, CASR plays an important role in maintaining cell membrane potential and homeostasis of metal ions such as Ca²⁺, Mg²⁺, and K⁺, regulating parathyroid hormone secretion, ion channel activation, and regulation of functional gene expression.

CASR Membrane Protein Introduction Fig.1 Structural basis for Mg²⁺/Ca²⁺ modulated CASR activities. (Chen, 2016)

Application of CASR Membrane Protein in Literature

Moon J.E., et al. De novo a novel variant of CaSR gene in a neonate with congenital hypoparathyroidism. Ann Pediatr Endocrinol Metab. 2018, 23(2): 107-111. PubMed ID: 29969884

The article showed that most patients with hereditary disease ADHH have a CASR gene mutation.
Dos Santos P.M.C., et al. Calcium-sensing receptor (CASR) modulates vacuolar H+-ATPase activity in a cell model of proximal tubule. Clin Exp Nephrol. 2018, 1-8. PubMed ID: 29961155

This article revealed that CASR can increase the vacuolar H + -ATPase activity of OKP cells, and the decrease of intracellular pH leads to an increase in intraluminal calcium ionization, which may enhance its reabsorption in the distal small tube segment and reduce the formation of calcium phosphate stones.
Sarem M., et al. Hyperstimulation of CASR in human MSCs by biomimetic apatite inhibits endochondral ossification via temporal down-regulation of PTH1R. Proc Natl Acad Sci. 2018, 115(27): E6135-E6144. PubMed ID: 29915064

The article demonstrated that the expression of CASR in human bone marrow-derived MSCs, CASR plays an important role in regulating MSC fate and bone formation pathway selection.
Tang L., et al. Calcimimetic acts on enteric neuronal CASR to reverse cholera toxin-induced intestinal electrolyte secretion. Sci Rep. 2018, 8(1): 7851. PubMed ID: 29777154

This article indicated that R568 is a calcimimetic agent that activates CASR, which acts on intestinal epithelial cells and reverses cholera toxin-induced fluid secretion.
Jain R.A., et al. A Forward Genetic Screen in Zebrafish Identifies the G-Protein-Coupled Receptor CASR as a Modulator of Sensorimotor Decision Making. Curr Biol. 2018, 28(9): 1357-1369. PubMed ID: 29681477

This article showed that CASR-promoting sensorimotor decisions are regulated by clathrin-mediated endocytosis by Gthi/o and Gαq/11 signaling.

CASR Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CASR antibody development services.

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Reference

Chen Zhang, et al. (2016). Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist. Science Advances.

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