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extracellular Ca+2-sensing receptor; CaSR; parathyroid cell Ca+2-sensing receptor; PCaR1 (CASR, GPRC2A, PCAR1)

Function: - senses changes in the extracellular concentration of Ca+2 - activity is mediated by a G-protein that activates a phosphatidylinositol-Ca+2 second messenger system - interacts with VCP & RNF19A - ubiquitinated by RNF19A; which induces proteasomal degradation Structure: - N-glycosylated - belongs to the G-protein coupled receptor 3 family - the extracellular domain of the Ca+2 receptor (605 aa length) is unusually long for serpentine receptors - the N-terminal Ca+2 binding site is thought to function as the Ca+2 receptor through a 'Venus Flytrap' like Ca+2-binding pocket. Compartment: cell membrane; multi-pass membrane protein Alternative splicing: named isoforms=2 Expression: - expressed in kidney - not expressed in brain, lung, liver, heart, skeletal muscle, or placenta Pathology: - defects in CASR are the cause of a) familial hypocalciuric hypercalcemia type 1 b) neonatal severe primary hyperparathyroidism c) autosomal dominant hypoparathyroidism d) chronic pancreatitis [5]

Related

autosomal dominant hypoparathyroidism; familial isolated hypoparathyroidism; autosomal dominant hypocalcemia Ca+2 familial hypocalciuric hypercalcemia type I neonatal severe primary hyperparathyroidism parathyroid

General

Ca+2 sensor or Ca+2 sensing receptor glycoprotein G-protein coupled receptor; serpentine receptor

Properties

SIZE: entity length = 1078 aa MW = 121 kD COMPARTMENT: plasma membrane MOTIF: exoplasmic domain {N-TERMINAL} exoplasmic domain {20-612} MOTIF: Ca+2-binding site SITE: N-TERMINAL MOTIF: N-glycosylation site {N90} N-glycosylation site {N130} N-glycosylation site {N261} N-glycosylation site {N287} N-glycosylation site {N386} N-glycosylation site {N400} N-glycosylation site {N446} N-glycosylation site {N468} N-glycosylation site {N488} N-glycosylation site {N541} N-glycosylation site {N594} glycosylation site transmembrane domain {613-635} binding site SITE: C-TERMINAL-CYS EFFECTOR-BOUND: palmitate BOUND-VIA: carboxylate cytoplasmic loop {636-649} transmembrane domain {650-670} exoplasmic loop {671-681} transmembrane domain {682-700} cytoplasmic loop {701-724} transmembrane domain {725-745} exoplasmic loop {746-769} transmembrane domain {770-792} cytoplasmic loop {793-805} cytoplasmic domain {C-TERMINAL} transmembrane domain {806-828} exoplasmic loop {829-836} transmembrane domain {837-862} cytoplasmic domain {863-1078} MOTIF: RNF19A interaction {880-900}

Database Correlations

OMIM correlations MORBIDMAP 601199 UniProt P41180 PFAM correlations Kegg hsa:846

References

  1. Conklin BR, Bourne HR. Homeostatic signals. Marriage of the flytrap and the serpent. Nature. 1994 Jan 6;367(6458):22. No abstract available. PMID: 8107768
  2. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=CASR
  3. SeattleSNPs http://pga.gs.washington.edu/data/casr/
  4. UniProt :accession P41180
  5. Medical Knowledge Self Assessment Program (MKSAP) 17, 18 American College of Physicians, Philadelphia 2015, 2018