Casr
entrez
12374
canonical
uniprot
Q9QY96
canonical
ensembl
ENSMUSG00000051980
resolver
ensp
ENSMUSP00000069080
resolver
ensp
ENSMUSP00000133500
resolver
ensp
ENSMUSP00000212783
resolver
genesymbol
Casr
resolver
genesymbol_syn
Gprc2a
resolver
uniprot
G3UX06
resolver
uniprot
O08968
resolver
uniprot
O88519
resolver
uniprot
Q9QY95
resolver
uniprot
Q9QZU8
resolver
uniprot
Q9R1D6
resolver
uniprot
Q9R1Y2
resolver
uniprot_entry
CASR_MOUSE
resolver
uniprot_sec
G3UX06
resolver
uniprot_sec
O08968
resolver
uniprot_sec
O88519
resolver
uniprot_sec
Q9QY95
resolver
uniprot_sec
Q9QZU8
resolver
uniprot_sec
Q9R1D6
resolver
uniprot_sec
Q9R1Y2
resolver
activity_regulation
ACTIVITY REGULATION: In resting state, adopts an open conformation, anion-binding promoting the inactive configuration. Upon aromatic amino acid-binding, the groove in the extracellular venus flytrap module is closed, thereby inducing the formation of a novel homodimer interface between subunits. Calcium ions stabilize the active state by enhancing homodimer interactions between membrane-proximal domains to fully activate the receptor. Upon activation, the homodimer adopts an asymmetric configuration of the 7-transmembrane region that primes one protomer for G protein coupling. G protein binding expands the transmembrane dimer interface; the restriction imposed by the receptor dimer, in combination with intracellular loop 2 (ICL2), enables G protein activation by facilitating conformational transition of G protein alpha. Coupling to different classes of G proteins results in distinct CASR-G protein interfaces. {ECO:0000250|UniProtKB:P41180}.
uniprot
proteins
amino_acid_sequence
MAWFGYCLALLALTWHSSAYGPDQRAQKKGDIILGGLFPIHFGVAAKDQDLKSRPESVECIRYNFRGFRWLQAMIFAIEEINSSPALLPNMTLGYRIFDTCNTVSKALEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSGVSTAVANLLGLFYIPQVSYASSSRLLSNKNQFKSFLRTIPNDEHQATAMADIIEYFRWNWVGTIAADDDYGRPGIEKFREEAEERDICIDFSELISQYSDEEEIQQVVEVIQNSTAKVIVVFSSGPDLEPLIKEIVRRNITGRIWLASEAWASSSLIAMPEYFHVVGGTIGFGLKAGQIPGFREFLQKVHPRKSVHNGFAKEFWEETFNCHLQDGAKGPLPVDTFVRSHEEGGNRLLNSSTAFRPLCTGDENINSVETPYMDYEHLRISYNVYLAVYSIAHALQDIYTCLPGRGLFTNGSCADIKKVEAWQVLKHLRHLNFTNNMGEQVTFDECGDLVGNYSIINWHLSPEDGSIVFKEVGYYNVYAKKGERLFINEGKILWSGFSREVPFSNCSRDCQAGTRKGIIEGEPTCCFECVECPDGEYSGETDASACDKCPDDFWSNENHTSCIAKEIEFLAWTEPFGIALTLFAVLGIFLTAFVLGVFIKFRNTPIVKATNRELSYLLLFSLLCCFSSSLFFIGEPQDWTCRLRQPAFGISFVLCISCILVKTNRVLLVFEAKIPTSFHRKWWGLNLQFLLVFLCTFMQIVICIIWLYTAPPSSYRNHELEDEIIFITCHEGSLMALGSLIGYTCLLAAICFFFAFKSRKLPENFNEAKFITFSMLIFFIVWISFIPAYASTYGKFVSAVEVIAILAASFGLLACIFFNKVYIILFKPSRNTIEEVRSSTAAHAFKVAARATLRRPNISRKRSSSLGGSTGSIPSSSISSKSNSEDRFPQPERQKQQQPLALTQQEQQQQPLTLQPQQQQQPQQPRCKQKVIFGSGTVTFSLSFDEPQKNAMAHRNSMRQNSLEAQKSNDTLNRHQALLPLQCAEADSEMTIQETGLQGPMVGDHQPEIESPDEMSPALVMSTSRSFVISGGGSSVTENILHS
uniprot
proteins
function
FUNCTION: G protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis (PubMed:23143333). Senses fluctuations in the circulating calcium concentration: activated by elevated circulating calcium, leading to decreased parathyroid hormone (PTH) secretion in parathyroid glands (PubMed:7493018). In kidneys, acts as a key regulator of renal tubular calcium resorption (PubMed:12671051). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (By similarity). CASR is coupled with different G(q)/G(11), G(i)/G(o)- or G(s)-classes of G proteins depending on the context (PubMed:23143333). In the parathyroid and kidney, CASR signals through G(q)/G(11) and G(i)/G(o) G proteins: G(q)/G(11) coupling activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers, while G(i)/G(o) coupling mediates inhibition of adenylate cyclase activity (PubMed:23143333). 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 (By similarity). Acts as an activator of the NLRP3 inflammasome via G(i)/G(o)-mediated signaling: down-regulation of cyclic AMP (cAMP) relieving NLRP3 inhibition by cAMP (PubMed:23143333). Acts as a regulator of proton-sensing receptor GPR68 in a seesaw manner: CASR-mediated signaling inhibits GPR68 signaling in response to extracellular calcium, while GPR68 inhibits CASR in presence of extracellular protons (PubMed:26261299). {ECO:0000250|UniProtKB:P41180, ECO:0000269|PubMed:12671051, ECO:0000269|PubMed:23143333, ECO:0000269|PubMed:26261299, ECO:0000269|PubMed:7493018}.
uniprot
proteins
mass_dalton
120903
uniprot
proteins
mutagenesis
MUTAGEN 723; /note="L->Q: In nuclear flecks (Nuf) mutant; gain-of-function mutant; mice develop cataracts and display ectopic calcification."; /evidence="ECO:0000269|PubMed:15347804
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Thr-888 by PKC impairs coupling with G(q)/G(11) G proteins, while it does not affect G(i)/G(o)-coupling. Phosphorylation at Ser-899 by PKA promote plasma membrane localization. {ECO:0000250|UniProtKB:P41180}.; PTM: Ubiquitinated by RNF19A; which induces proteasomal degradation. {ECO:0000250|UniProtKB:P41180}.
uniprot
proteins
protein_family
G protein-coupled receptor 3 family
uniprot
proteins
pubmed
10579354
uniprot
proteins
pubmed
10625662
uniprot
proteins
pubmed
10652312
uniprot
proteins
pubmed
12671051
uniprot
proteins
pubmed
15347804
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23143333
uniprot
proteins
pubmed
26261299
uniprot
proteins
pubmed
7493018
uniprot
proteins
pubmed
9076582
uniprot
proteins
sequence_length
1079
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15347804}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 611..636; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:P41180"; TRANSMEM 649..668; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:P41180"; TRANSMEM 675..698; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:P41180"; TRANSMEM 723..745; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:P41180"; TRANSMEM 770..789; /note="Helical; Name=5"; /evidence="ECO:0000250|UniProtKB:P41180"; TRANSMEM 806..828; /note="Helical; Name=6"; /evidence="ECO:0000250|UniProtKB:P41180"; TRANSMEM 833..854; /note="Helical; Name=7"; /evidence="ECO:0000250|UniProtKB:P41180
uniprot
proteins