Casr
entrez
24247
canonical
uniprot
P48442
canonical
ensembl
ENSRNOG00000002265
resolver
ensembl
ENSRNOG00055017089
resolver
ensembl
ENSRNOG00060026973
resolver
ensembl
ENSRNOG00065018590
resolver
ensp
ENSRNOP00000003092
resolver
ensp
ENSRNOP00055023361
resolver
ensp
ENSRNOP00060038904
resolver
ensp
ENSRNOP00065024881
resolver
enst
ENSRNOT00000003092
resolver
enst
ENSRNOT00055029017
resolver
enst
ENSRNOT00060046779
resolver
enst
ENSRNOT00065031234
resolver
genesymbol
Casr
resolver
genesymbol_syn
Gprc2a
resolver
genesymbol_syn
Pcar1
resolver
uniprot_entry
CASR_RAT
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
MASYSCCLALLALAWHSSAYGPDQRAQKKGDIILGGLFPIHFGVAAKDQDLKSRPESVECIRYNFRGFRWLQAMIFAIEEINSSPSLLPNMTLGYRIFDTCNTVSKALEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSGVSTAVANLLGLFYIPQVSYASSSRLLSNKNQYKSFLRTIPNDEHQATAMADIIEYFRWNWVGTIAADDDYGRPGIEKFREEAEERDICIDFSELISQYSDEEEIQQVVEVIQNSTAKVIVVFSSGPDLEPLIKEIVRRNITGRIWLASEAWASSSLIAMPEYFHVVGGTIGFGLKAGQIPGFREFLQKVHPRKSVHNGFAKEFWEETFNCHLQEGAKGPLPVDTFVRSHEEGGNRLLNSSTAFRPLCTGDENINSVETPYMDYEHLRISYNVYLAVYSIAHALQDIYTCLPGRGLFTNGSCADIKKVEAWQVLKHLRHLNFTNNMGEQVTFDECGDLVGNYSIINWHLSPEDGSIVFKEVGYYNVYAKKGERLFINEEKILWSGFSREVPFSNCSRDCQAGTRKGIIEGEPTCCFECVECPDGEYSGETDASACDKCPDDFWSNENHTSCIAKEIEFLAWTEPFGIALTLFAVLGIFLTAFVLGVFIKFRNTPIVKATNRELSYLLLFSLLCCFSSSLFFIGEPQDWTCRLRQPAFGISFVLCISCILVKTNRVLLVFEAKIPTSFHRKWWGLNLQFLLVFLCTFMQILICIIWLYTAPPSSYRNHELEDEIIFITCHEGSLMALGSLIGYTCLLAAICFFFAFKSRKLPENFNEAKFITFSMLIFFIVWISFIPAYASTYGKFVSAVEVIAILAASFGLLACIFFNKVYIILFKPSRNTIEEVRSSTAAHAFKVAARATLRRPNISRKRSSSLGGSTGSIPSSSISSKSNSEDRFPQPERQKQQQPLSLTQQEQQQQPLTLHPQQQQQPQQPRCKQKVIFGSGTVTFSLSFDEPQKNAMAHRNSMRQNSLEAQRSNDTLGRHQALLPLQCADADSEMTIQETGLQGPMVGDHQPEMESSDEMSPALVMSTSRSFVISGGGSSVTENVLHS
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:22886306, PubMed:7816802). Senses fluctuations in the circulating calcium concentration: activated by elevated circulating calcium, leading to decreased parathyroid hormone (PTH) secretion in parathyroid glands (By similarity). In kidneys, acts as a key regulator of renal tubular calcium resorption (PubMed:22886306). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. CASR is coupled with different G(q)/G(11), G(i)/G(o)- or G(s)-classes of G proteins depending on the context. 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. 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. 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P41180, ECO:0000250|UniProtKB:Q9QY96, ECO:0000269|PubMed:22886306, ECO:0000269|PubMed:7816802}.
uniprot
proteins
mass_dalton
120868
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
17623778
uniprot
proteins
pubmed
22886306
uniprot
proteins
pubmed
7724534
uniprot
proteins
pubmed
7816802
uniprot
proteins
sequence_length
1079
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P41180}; 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