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9.A.14.7.2
Extracellular calcium-sensing receptor of 1078 aas and 7 TMSs, CASR, GPCRC2A, PCAR1.  It senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis (Kim et al. 2016). In the inner ear membranous labyrinth, CaSR localizes exclusively tp mitochondrion-rich cell, suggesting a unique role of the endolymphatic sac epithelium in CaSR-mediated sensing and control(Bächinger et al. 2019).  

Accession Number:P41180
Protein Name:Extracellular calcium-sensing receptor
Length:1078
Molecular Weight:120674.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:7
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate NONE

Cross database links:

DIP: DIP-5975N DIP-5975N
Entrez Gene ID: 846   
Pfam: PF00003    PF01094    PF07562   
KEGG: hsa:846    hsa:846   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0004930 F:G-protein coupled receptor activity
GO:0004435 F:phosphatidylinositol phospholipase C activity
GO:0005515 F:protein binding
GO:0009653 P:anatomical structure morphogenesis
GO:0070509 P:calcium ion import
GO:0019722 P:calcium-mediated signaling
GO:0006874 P:cellular calcium ion homeostasis
GO:0007635 P:chemosensory behavior
GO:0005513 P:detection of calcium ion
GO:0001503 P:ossification

References (86)

[1] “Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs.”  Garrett J.E.et.al.   7759551
[2] “Molecular cloning of a putative Ca(2+)-sensing receptor cDNA from human kidney.”  Aida K.et.al.   7677761
[3] “Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion.”  Freichel M.et.al.   8756555
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene.”  Aida K.et.al.   7673400
[6] “Changes in calcium responsiveness and handling during keratinocyte differentiation. Potential role of the calcium receptor.”  Bikle D.D.et.al.   8613532
[7] “Calcium-sensing receptor ubiquitination and degradation mediated by the E3 ubiquitin ligase dorfin.”  Huang Y.et.al.   16513638
[8] “Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.”  Pollak M.R.et.al.   7916660
[9] “Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation.”  Pollak M.R.et.al.   7874174
[10] “Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia.”  Chou Y.-H.W.et.al.   7726161
[11] “Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism.”  Pearce S.H.S.et.al.   8675635
[12] “The Ca(2+)-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism.”  Lovlie R.et.al.   8698326
[13] “Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism.”  Baron J.et.al.   8733126
[14] “A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor.”  Pearce S.H.S.et.al.   8813042
[15] “A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia.”  Ward B.K.et.al.   9298824
[16] “Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor.”  De Luca F.et.al.   9253358
[17] “Two novel missense mutations in calcium-sensing receptor gene associated with neonatal severe hyperparathyroidism.”  Kobayashi M.et.al.   9253359
[18] “Familial hypoparathyroidism: identification of a novel gain of function mutation in transmembrane domain 5 of the calcium-sensing receptor.”  Watanabe T.et.al.   9661634
[19] “An adult patient with severe hypercalcaemia and hypocalciuria due to a novel homozygous inactivating mutation of calcium-sensing receptor.”  Chikatsu N.et.al.   10468915
[20] “A novel activating mutation in calcium-sensing receptor gene associated with a family of autosomal dominant hypocalcemia.”  Okazaki R.et.al.   9920108
[21] “Autosomal dominant hypoparathyroidism associated with short stature and premature osteoarthritis.”  Stock J.L.et.al.   10487661
[22] “A986S polymorphism of the calcium-sensing receptor and circulating calcium concentrations.”  Cole D.E.C.et.al.   10023897
[23] “Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor.”  Carling T.et.al.   10843194
[24] “A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia.”  Nakayama T.et.al.   11762699
[25] “Association between total serum calcium and the A986S polymorphism of the calcium-sensing receptor gene.”  Cole D.E.C.et.al.   11161843
[26] “A family of autosomal dominant hypocalcemia with a positive correlation between serum calcium and magnesium: identification of a novel gain of function mutation (Ser(820)Phe) in the calcium-sensing receptor.”  Nagase T.et.al.   12050233
[27] “Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene.”  Sato K.et.al.   12107202
[28] “Association between activating mutations of calcium-sensing receptor and Bartter's syndrome.”  Watanabe S.et.al.   12241879
[29] “Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor.”  Tan Y.M.et.al.   12574188
[30] “Recurrent familial hypocalcemia due to germline mosaicism for an activating mutation of the calcium-sensing receptor gene.”  Hendy G.N.et.al.   12915654
[31] “Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor.”  Scillitani A.et.al.   15531522
[32] “Severe hypercalcemia in a 9-year-old Brazilian girl due to a novel inactivating mutation of the calcium-sensing receptor.”  Miyashiro K.et.al.   15579740
[33] “Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications.”  Warner J.et.al.   14985373
[34] “A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia.”  Uckun-Kitapci A.et.al.   15551332
[35] “Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia.”  Pidasheva S.et.al.   15879434
[36] “Functional characterization of calcium-sensing receptor codon 227 mutations presenting as either familial (benign) hypocalciuric hypercalcemia or neonatal hyperparathyroidism.”  Wystrychowski A.et.al.   15572418
[37] “Identification of a novel inactivating R465Q mutation of the calcium-sensing receptor.”  Leech C.et.al.   16598859
[38] “A hypocalcemic child with a novel activating mutation of the calcium-sensing receptor gene: successful treatment with recombinant human parathyroid hormone.”  Mittelman S.D.et.al.   16608894
[39] “Identification and functional characterization of a novel mutation in the calcium-sensing receptor gene in familial hypocalciuric hypercalcemia: modulation of clinical severity by vitamin D status.”  Zajickova K.et.al.   17473068
[40] “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.”  Nissen P.H.et.al.   17698911
[41] “An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene.”  Kapoor A.et.al.   18756473
[42] “A homozygous inactivating calcium-sensing receptor mutation, Pro339Thr, is associated with isolated primary hyperparathyroidism: correlation between location of mutations and severity of hypercalcaemia.”  Hannan F.M.et.al.   20846291
[43] “Familial hypocalciuric hypercalcemia: new mutation in the CASR gene converting valine 697 to methionine.”  Aparicio Lopez C.et.al.   21643651
[44] “Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs.”  Garrett J.E.et.al.   7759551
[45] “Molecular cloning of a putative Ca(2+)-sensing receptor cDNA from human kidney.”  Aida K.et.al.   7677761
[46] “Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion.”  Freichel M.et.al.   8756555
[47] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[48] “Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene.”  Aida K.et.al.   7673400
[49] “Changes in calcium responsiveness and handling during keratinocyte differentiation. Potential role of the calcium receptor.”  Bikle D.D.et.al.   8613532
[50] “Calcium-sensing receptor ubiquitination and degradation mediated by the E3 ubiquitin ligase dorfin.”  Huang Y.et.al.   16513638
[51] “Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.”  Pollak M.R.et.al.   7916660
[52] “Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation.”  Pollak M.R.et.al.   7874174
[53] “Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia.”  Chou Y.-H.W.et.al.   7726161
[54] “Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism.”  Pearce S.H.S.et.al.   8675635
[55] “The Ca(2+)-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism.”  Lovlie R.et.al.   8698326
[56] “Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism.”  Baron J.et.al.   8733126
[57] “A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor.”  Pearce S.H.S.et.al.   8813042
[58] “A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia.”  Ward B.K.et.al.   9298824
[59] “Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor.”  De Luca F.et.al.   9253358
[60] “Two novel missense mutations in calcium-sensing receptor gene associated with neonatal severe hyperparathyroidism.”  Kobayashi M.et.al.   9253359
[61] “Familial hypoparathyroidism: identification of a novel gain of function mutation in transmembrane domain 5 of the calcium-sensing receptor.”  Watanabe T.et.al.   9661634
[62] “An adult patient with severe hypercalcaemia and hypocalciuria due to a novel homozygous inactivating mutation of calcium-sensing receptor.”  Chikatsu N.et.al.   10468915
[63] “A novel activating mutation in calcium-sensing receptor gene associated with a family of autosomal dominant hypocalcemia.”  Okazaki R.et.al.   9920108
[64] “Autosomal dominant hypoparathyroidism associated with short stature and premature osteoarthritis.”  Stock J.L.et.al.   10487661
[65] “A986S polymorphism of the calcium-sensing receptor and circulating calcium concentrations.”  Cole D.E.C.et.al.   10023897
[66] “Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor.”  Carling T.et.al.   10843194
[67] “A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia.”  Nakayama T.et.al.   11762699
[68] “Association between total serum calcium and the A986S polymorphism of the calcium-sensing receptor gene.”  Cole D.E.C.et.al.   11161843
[69] “A family of autosomal dominant hypocalcemia with a positive correlation between serum calcium and magnesium: identification of a novel gain of function mutation (Ser(820)Phe) in the calcium-sensing receptor.”  Nagase T.et.al.   12050233
[70] “Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene.”  Sato K.et.al.   12107202
[71] “Association between activating mutations of calcium-sensing receptor and Bartter's syndrome.”  Watanabe S.et.al.   12241879
[72] “Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor.”  Tan Y.M.et.al.   12574188
[73] “Recurrent familial hypocalcemia due to germline mosaicism for an activating mutation of the calcium-sensing receptor gene.”  Hendy G.N.et.al.   12915654
[74] “Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor.”  Scillitani A.et.al.   15531522
[75] “Severe hypercalcemia in a 9-year-old Brazilian girl due to a novel inactivating mutation of the calcium-sensing receptor.”  Miyashiro K.et.al.   15579740
[76] “Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications.”  Warner J.et.al.   14985373
[77] “A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia.”  Uckun-Kitapci A.et.al.   15551332
[78] “Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia.”  Pidasheva S.et.al.   15879434
[79] “Functional characterization of calcium-sensing receptor codon 227 mutations presenting as either familial (benign) hypocalciuric hypercalcemia or neonatal hyperparathyroidism.”  Wystrychowski A.et.al.   15572418
[80] “Identification of a novel inactivating R465Q mutation of the calcium-sensing receptor.”  Leech C.et.al.   16598859
[81] “A hypocalcemic child with a novel activating mutation of the calcium-sensing receptor gene: successful treatment with recombinant human parathyroid hormone.”  Mittelman S.D.et.al.   16608894
[82] “Identification and functional characterization of a novel mutation in the calcium-sensing receptor gene in familial hypocalciuric hypercalcemia: modulation of clinical severity by vitamin D status.”  Zajickova K.et.al.   17473068
[83] “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.”  Nissen P.H.et.al.   17698911
[84] “An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene.”  Kapoor A.et.al.   18756473
[85] “A homozygous inactivating calcium-sensing receptor mutation, Pro339Thr, is associated with isolated primary hyperparathyroidism: correlation between location of mutations and severity of hypercalcaemia.”  Hannan F.M.et.al.   20846291
[86] “Familial hypocalciuric hypercalcemia: new mutation in the CASR gene converting valine 697 to methionine.”  Aparicio Lopez C.et.al.   21643651
Structure:
5FBH   5FBK   5K5S   5K5T     

External Searches:

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence
1:	MAFYSCCWVL LALTWHTSAY GPDQRAQKKG DIILGGLFPI HFGVAAKDQD LKSRPESVEC 
61:	IRYNFRGFRW LQAMIFAIEE INSSPALLPN LTLGYRIFDT CNTVSKALEA TLSFVAQNKI 
121:	DSLNLDEFCN CSEHIPSTIA VVGATGSGVS TAVANLLGLF YIPQVSYASS SRLLSNKNQF 
181:	KSFLRTIPND EHQATAMADI IEYFRWNWVG TIAADDDYGR PGIEKFREEA EERDICIDFS 
241:	ELISQYSDEE EIQHVVEVIQ NSTAKVIVVF SSGPDLEPLI KEIVRRNITG KIWLASEAWA 
301:	SSSLIAMPQY FHVVGGTIGF ALKAGQIPGF REFLKKVHPR KSVHNGFAKE FWEETFNCHL 
361:	QEGAKGPLPV DTFLRGHEES GDRFSNSSTA FRPLCTGDEN ISSVETPYID YTHLRISYNV 
421:	YLAVYSIAHA LQDIYTCLPG RGLFTNGSCA DIKKVEAWQV LKHLRHLNFT NNMGEQVTFD 
481:	ECGDLVGNYS IINWHLSPED GSIVFKEVGY YNVYAKKGER LFINEEKILW SGFSREVPFS 
541:	NCSRDCLAGT RKGIIEGEPT CCFECVECPD GEYSDETDAS ACNKCPDDFW SNENHTSCIA 
601:	KEIEFLSWTE PFGIALTLFA VLGIFLTAFV LGVFIKFRNT PIVKATNREL SYLLLFSLLC 
661:	CFSSSLFFIG EPQDWTCRLR QPAFGISFVL CISCILVKTN RVLLVFEAKI PTSFHRKWWG 
721:	LNLQFLLVFL CTFMQIVICV IWLYTAPPSS YRNQELEDEI IFITCHEGSL MALGFLIGYT 
781:	CLLAAICFFF AFKSRKLPEN FNEAKFITFS MLIFFIVWIS FIPAYASTYG KFVSAVEVIA 
841:	ILAASFGLLA CIFFNKIYII LFKPSRNTIE EVRCSTAAHA FKVAARATLR RSNVSRKRSS 
901:	SLGGSTGSTP SSSISSKSNS EDPFPQPERQ KQQQPLALTQ QEQQQQPLTL PQQQRSQQQP 
961:	RCKQKVIFGS GTVTFSLSFD EPQKNAMAHR NSTHQNSLEA QKSSDTLTRH QPLLPLQCGE 
1021:	TDLDLTVQET GLQGPVGGDQ RPEVEDPEEL SPALVVSSSQ SFVISGGGST VTENVVNS