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P41180

- CASR_HUMAN

UniProt

P41180 - CASR_HUMAN

Protein

Extracellular calcium-sensing receptor

Gene

CASR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 159 (01 Oct 2014)
      Sequence version 2 (01 Nov 1995)
      Previous versions | rss
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    Functioni

    Senses changes in the extracellular concentration of calcium ions. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system.

    GO - Molecular functioni

    1. G-protein coupled receptor activity Source: ProtInc
    2. phosphatidylinositol phospholipase C activity Source: ProtInc
    3. protein binding Source: IntAct

    GO - Biological processi

    1. anatomical structure morphogenesis Source: ProtInc
    2. calcium ion import Source: UniProtKB
    3. cellular calcium ion homeostasis Source: ProtInc
    4. chemosensory behavior Source: ProtInc
    5. detection of calcium ion Source: ProtInc
    6. G-protein coupled receptor signaling pathway Source: ProtInc
    7. metabolic process Source: GOC
    8. ossification Source: ProtInc

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Enzyme and pathway databases

    ReactomeiREACT_18283. G alpha (q) signalling events.
    REACT_18319. Class C/3 (Metabotropic glutamate/pheromone receptors).
    REACT_19231. G alpha (i) signalling events.

    Protein family/group databases

    TCDBi9.A.14.7.2. the g-protein-coupled receptor (gpcr) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Extracellular calcium-sensing receptor
    Short name:
    CaSR
    Alternative name(s):
    Parathyroid cell calcium-sensing receptor 1
    Short name:
    PCaR1
    Gene namesi
    Name:CASR
    Synonyms:GPRC2A, PCAR1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:1514. CASR.

    Subcellular locationi

    Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

    GO - Cellular componenti

    1. integral component of plasma membrane Source: ProtInc
    2. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Hypocalciuric hypercalcemia, familial 1 (HHC1) [MIM:145980]: A form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. It is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level. Hypermagnesemia is typically present. Affected individuals are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults.12 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti11 – 111L → S in HHC1; demonstrates reduced intracellular and plasma membrane expression and signaling to the MAPK pathway in response to extracellular calcium relative to wild-type; fails to be inserted in the microsomes and does not undergo proper glycosylation. 1 Publication
    VAR_058046
    Natural varianti13 – 131L → P in HHC1; has a dose-response curve shifted to the right relative to that of wild-type; demonstrates reduced intracellular and plasma membrane expression and signaling to the MAPK pathway in response to extracellular calcium relative to wild-type; fails to be inserted in the microsomes and does not undergo proper glycosylation. 2 Publications
    VAR_058047
    Natural varianti21 – 211G → R in HHC1. 1 Publication
    VAR_058049
    Natural varianti39 – 391P → A in HHC1. 1 Publication
    VAR_003585
    Natural varianti62 – 621R → M in HHC1 and NSHPT; mild. 1 Publication
    VAR_003586
    Natural varianti66 – 661R → C in HHC1. 1 Publication
    VAR_003587
    Natural varianti138 – 1381T → M in HHC1. 1 Publication
    VAR_003590
    Natural varianti143 – 1431G → E in HHC1. 1 Publication
    VAR_003591
    Natural varianti171 – 1711S → N in HHC1. 1 Publication
    VAR_058056
    Natural varianti174 – 1741L → R in HHC1. 1 Publication
    VAR_003592
    Natural varianti180 – 1801F → C in HHC1; although the mutant receptor is expressed normally at the cell surface it is unresponsive with respect to intracellular signaling (MAPK activation) to increases in extracellular calcium concentrations. 1 Publication
    VAR_058057
    Natural varianti185 – 1851R → Q in HHC1. 1 Publication
    VAR_003593
    Natural varianti221 – 2211P → Q in HHC1. 1 Publication
    VAR_058059
    Natural varianti225 – 2251K → T in HHC1. 1 Publication
    VAR_058060
    Natural varianti227 – 2271R → Q in HHC1; impaired in their MAPK response to increasing extracellular calcium concentrations; less markedly impaired relative to wild-type then Leu-227; when cotransfected with wild-type the curve is right-shifted intermediate to the curve for wild-type. 2 Publications
    VAR_003595
    Natural varianti271 – 2711S → F in HHC1. 1 Publication
    VAR_058062
    Natural varianti297 – 2971E → K in HHC1 and NSHPT. 1 Publication
    VAR_003596
    Natural varianti397 – 3971G → R in HHC1. 1 Publication
    VAR_058063
    Natural varianti465 – 4651R → Q in HHC1; loss-of-function mutation; the quantity of the mutant receptor is higher than that of the wild-type receptor; dose-response curves show that the mutation significantly reduces the sensitivity of the receptor to extracellular calcium concentrations. 1 Publication
    VAR_058064
    Natural varianti509 – 5091G → R in HHC1. 1 Publication
    Corresponds to variant rs193922423 [ dbSNP | Ensembl ].
    VAR_058065
    Natural varianti553 – 5531G → R in HHC1. 1 Publication
    VAR_058066
    Natural varianti555 – 5551I → V in HHC1. 1 Publication
    VAR_058067
    Natural varianti557 – 5571G → E in HHC1. 1 Publication
    VAR_012649
    Natural varianti562 – 5621C → Y in HHC1. 1 Publication
    VAR_058068
    Natural varianti582 – 5821C → F in HHC1. 1 Publication
    VAR_058069
    Natural varianti623 – 6231G → D in HHC1. 1 Publication
    VAR_058072
    Natural varianti670 – 6701G → R in HHC1. 1 Publication
    VAR_058074
    Natural varianti697 – 6971V → M in HHC1. 1 Publication
    VAR_065494
    Natural varianti728 – 7281V → F in HHC1. 1 Publication
    VAR_058076
    Natural varianti742 – 7421W → R in HHC1. 1 Publication
    VAR_058077
    Natural varianti795 – 7951R → W in HHC1. 1 Publication
    VAR_003599
    Natural varianti886 – 8861R → W in HHC1. 1 Publication
    VAR_058084
    Hyperparathyroidism, neonatal severe (NSHPT) [MIM:239200]: A disorder characterized by severe hypercalcemia, bone demineralization, and failure to thrive usually manifesting in the first 6 months of life. If untreated, NSHPT can be a devastating neurodevelopmental disorder, which in some cases is lethal without parathyroidectomy.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti62 – 621R → M in HHC1 and NSHPT; mild. 1 Publication
    VAR_003586
    Natural varianti227 – 2271R → L in NSHPT; impaired in their MAPK response to increasing extracellular calcium concentrations; more markedly impaired relative to wild-type then Gln-227; when cotransfected with wild-type the curve is right-shifted intermediate to the curve for wild-type. 1 Publication
    Corresponds to variant rs28936684 [ dbSNP | Ensembl ].
    VAR_003594
    Natural varianti297 – 2971E → K in HHC1 and NSHPT. 1 Publication
    VAR_003596
    Natural varianti582 – 5821C → Y in NSHPT. 2 Publications
    VAR_003597
    Natural varianti670 – 6701G → E in NSHPT. 1 Publication
    VAR_058073
    Hypocalcemia, autosomal dominant 1 (HYPOC1) [MIM:601198]: A disorder of mineral homeostasis characterized by blood calcium levels below normal, and low or normal serum parathyroid hormone concentrations. Disease manifestations include mild or asymptomatic hypocalcemia, paresthesias, carpopedal spasm, seizures, hypercalciuria with nephrocalcinosis or kidney stones, and ectopic and basal ganglia calcifications. Few patients manifest hypocalcemia and features of Bartter syndrome, including hypomagnesemia, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronemia.14 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti47 – 471K → N in HYPOC1; the EC(50) of the mutant is significantly lower than that of wild-type. 1 Publication
    VAR_058050
    Natural varianti116 – 1161A → T in HYPOC1. 1 Publication
    VAR_003588
    Natural varianti118 – 1181N → K in HYPOC1; the mutation shifts the concentration-response curve to the left and increases maximal activity. 2 Publications
    VAR_058051
    Natural varianti125 – 1251L → P in HYPOC1; shifts the concentration-response curve of calcium ions to the left. 1 Publication
    VAR_058052
    Natural varianti127 – 1271E → A in HYPOC1. 1 Publication
    VAR_003589
    Natural varianti128 – 1281F → L in HYPOC1; there is a shift in the dose-response curve so that the extracellular calcium concentration needed to produce half-maximal increase in total inositol phosphate in the cells is significantly lower than the one required for the wild-type receptor. 1 Publication
    VAR_058053
    Natural varianti131 – 1311C → W in HYPOC1; associated with clinical features of Bartter syndrome. 1 Publication
    VAR_058054
    Natural varianti151 – 1511T → M in HYPOC1; there is a shift in the dose-response curve so that the extracellular calcium concentration needed to produce half-maximal increase in total inositol phosphate in the cells is significantly lower than the one required for the wild-type receptor. 2 Publications
    VAR_058055
    Natural varianti191 – 1911E → K in HYPOC1; there is a shift in the dose-response curve so that the extracellular calcium concentration needed to produce half-maximal increase in total inositol phosphate in the cells is significantly lower than the one required for the wild-type receptor. 1 Publication
    VAR_058058
    Natural varianti604 – 6041E → K in HYPOC1; there is a significant leftward shift in the concentration response curves for the effects of extracellular calcium on both intracellular calcium mobilization and MAPK activity. 1 Publication
    VAR_058070
    Natural varianti612 – 6121F → S in HYPOC1. 1 Publication
    VAR_058071
    Natural varianti616 – 6161L → V in HYPOC1; does not affect the total accumulation of inositol phosphates as a function of extracellular calcium concentrations in transfected cells. 1 Publication
    VAR_015414
    Natural varianti681 – 6811Q → H in HYPOC1. 1 Publication
    VAR_003598
    Natural varianti727 – 7271L → Q in HYPOC1; the mutant receptor demonstrates a significant leftward shift in the extracellular calcium/intracellular signaling dose-response curve versus that for the wild-type receptor. 1 Publication
    VAR_058075
    Natural varianti767 – 7671E → K in HYPOC1. 1 Publication
    VAR_021019
    Natural varianti773 – 7731L → R in HYPOC1; the mutation shifts the concentration-response curve to the left and increases maximal activity. 1 Publication
    VAR_058078
    Natural varianti788 – 7881F → C in HYPOC1; leftward shift in the concentration-response curve for the mutant receptor; cells cotransfected with both the wild-type and the mutant receptor show an EC(50) similar to the mutant; a gain-of-function mutation rendering the receptor more sensitive than normal to activation. 1 Publication
    VAR_058079
    Natural varianti788 – 7881F → L in HYPOC1; induces a significant shift to the left relative to the wild-type protein in the MAPK response to increasing extracellular calcium concentrations. 1 Publication
    VAR_058080
    Natural varianti806 – 8061F → S in HYPOC1; does not produce a significant activating effect; decreased cell surface receptor expression. 2 Publications
    VAR_003600
    Natural varianti820 – 8201S → F in HYPOC1; the concentration-response curve of the mutant receptor is left-shifted and its EC(50) is significantly lower than that of the wild-type. 1 Publication
    VAR_058081
    Natural varianti843 – 8431A → E in HYPOC1; also in HYPOC1 associated with clinical features of Bartter syndrome; shifts the concentration-response curve of calcium ions to the left. 2 Publications
    VAR_058082
    Epilepsy, idiopathic generalized 8 (EIG8) [MIM:612899]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Seizure types are variable, but include myoclonic seizures, absence seizures, febrile seizures, complex partial seizures, and generalized tonic-clonic seizures.1 Publication
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti354 – 3541E → A in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication
    VAR_060206
    Natural varianti686 – 6861I → V in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication
    VAR_060207
    Natural varianti898 – 8981R → Q in EIG8. 1 Publication
    VAR_060208
    Natural varianti988 – 9881A → G in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication
    VAR_060209
    Natural varianti988 – 9881A → V in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication
    VAR_060210
    Homozygous defects in CASR can be a cause of primary hyperparathyroidism in adulthood. Patients suffer from osteoporosis and renal calculi, have marked hypercalcemia and increased serum PTH concentrations.

    Keywords - Diseasei

    Disease mutation, Epilepsy

    Organism-specific databases

    MIMi145980. phenotype.
    239200. phenotype.
    601198. phenotype.
    601199. gene+phenotype.
    612899. phenotype.
    Orphaneti428. Autosomal dominant hypocalcemia.
    263417. Bartter syndrome with hypocalcemia.
    93372. Familial hypocalciuric hypercalcemia type 1.
    189466. Familial isolated hypoparathyroidism due to impaired PTH secretion.
    417. Neonatal severe primary hyperparathyroidism.
    PharmGKBiPA26097.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1919Sequence AnalysisAdd
    BLAST
    Chaini20 – 10781059Extracellular calcium-sensing receptorPRO_0000012946Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi90 – 901N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi130 – 1301N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi261 – 2611N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi287 – 2871N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi386 – 3861N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi400 – 4001N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi446 – 4461N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi468 – 4681N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi488 – 4881N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi541 – 5411N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi594 – 5941N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    N-glycosylated.2 Publications
    Ubiquitinated by RNF19A; which induces proteasomal degradation.1 Publication

    Keywords - PTMi

    Glycoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP41180.
    PRIDEiP41180.

    PTM databases

    PhosphoSiteiP41180.

    Expressioni

    Tissue specificityi

    Expressed in the temporal lobe, frontal lobe, parietal lobe, hippocampus, and cerebellum. Also found in kidney, lung, liver, heart, skeletal muscle, placenta.1 Publication

    Gene expression databases

    ArrayExpressiP41180.
    BgeeiP41180.
    CleanExiHS_CASR.
    GenevestigatoriP41180.

    Organism-specific databases

    HPAiHPA039686.

    Interactioni

    Subunit structurei

    Interacts with VCP and RNF19A. Interacts with ARRB1 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    TMED2Q153633EBI-4400127,EBI-998485

    Protein-protein interaction databases

    BioGridi107296. 10 interactions.
    DIPiDIP-5975N.
    IntActiP41180. 1 interaction.
    MINTiMINT-201342.
    STRINGi9606.ENSP00000296154.

    Structurei

    3D structure databases

    ProteinModelPortaliP41180.
    SMRiP41180. Positions 26-493, 603-864.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini20 – 612593ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini636 – 64914CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini671 – 68111ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini701 – 72424CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini746 – 76924ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini793 – 80513CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini829 – 8368ExtracellularSequence Analysis
    Topological domaini863 – 1078216CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei613 – 63523Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei650 – 67021Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei682 – 70019Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei725 – 74521Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei770 – 79223Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei806 – 82823Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei837 – 86226Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni880 – 90021Interaction with RNF19AAdd
    BLAST

    Sequence similaritiesi

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG295200.
    HOVERGENiHBG052876.
    KOiK04612.
    OrthoDBiEOG7DZ8J8.
    PhylomeDBiP41180.

    Family and domain databases

    InterProiIPR001828. ANF_lig-bd_rcpt.
    IPR000337. GPCR_3.
    IPR011500. GPCR_3_9-Cys_dom.
    IPR017978. GPCR_3_C.
    IPR017979. GPCR_3_CS.
    IPR028082. Peripla_BP_I.
    [Graphical view]
    PfamiPF00003. 7tm_3. 1 hit.
    PF01094. ANF_receptor. 1 hit.
    PF07562. NCD3G. 1 hit.
    [Graphical view]
    PRINTSiPR00248. GPCRMGR.
    SUPFAMiSSF53822. SSF53822. 1 hit.
    PROSITEiPS00979. G_PROTEIN_RECEP_F3_1. 1 hit.
    PS00980. G_PROTEIN_RECEP_F3_2. 1 hit.
    PS00981. G_PROTEIN_RECEP_F3_3. 1 hit.
    PS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P41180-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAFYSCCWVL LALTWHTSAY GPDQRAQKKG DIILGGLFPI HFGVAAKDQD     50
    LKSRPESVEC IRYNFRGFRW LQAMIFAIEE INSSPALLPN LTLGYRIFDT 100
    CNTVSKALEA TLSFVAQNKI DSLNLDEFCN CSEHIPSTIA VVGATGSGVS 150
    TAVANLLGLF YIPQVSYASS SRLLSNKNQF KSFLRTIPND EHQATAMADI 200
    IEYFRWNWVG TIAADDDYGR PGIEKFREEA EERDICIDFS ELISQYSDEE 250
    EIQHVVEVIQ NSTAKVIVVF SSGPDLEPLI KEIVRRNITG KIWLASEAWA 300
    SSSLIAMPQY FHVVGGTIGF ALKAGQIPGF REFLKKVHPR KSVHNGFAKE 350
    FWEETFNCHL QEGAKGPLPV DTFLRGHEES GDRFSNSSTA FRPLCTGDEN 400
    ISSVETPYID YTHLRISYNV YLAVYSIAHA LQDIYTCLPG RGLFTNGSCA 450
    DIKKVEAWQV LKHLRHLNFT NNMGEQVTFD ECGDLVGNYS IINWHLSPED 500
    GSIVFKEVGY YNVYAKKGER LFINEEKILW SGFSREVPFS NCSRDCLAGT 550
    RKGIIEGEPT CCFECVECPD GEYSDETDAS ACNKCPDDFW SNENHTSCIA 600
    KEIEFLSWTE PFGIALTLFA VLGIFLTAFV LGVFIKFRNT PIVKATNREL 650
    SYLLLFSLLC CFSSSLFFIG EPQDWTCRLR QPAFGISFVL CISCILVKTN 700
    RVLLVFEAKI PTSFHRKWWG LNLQFLLVFL CTFMQIVICV IWLYTAPPSS 750
    YRNQELEDEI IFITCHEGSL MALGFLIGYT CLLAAICFFF AFKSRKLPEN 800
    FNEAKFITFS MLIFFIVWIS FIPAYASTYG KFVSAVEVIA ILAASFGLLA 850
    CIFFNKIYII LFKPSRNTIE EVRCSTAAHA FKVAARATLR RSNVSRKRSS 900
    SLGGSTGSTP SSSISSKSNS EDPFPQPERQ KQQQPLALTQ QEQQQQPLTL 950
    PQQQRSQQQP RCKQKVIFGS GTVTFSLSFD EPQKNAMAHR NSTHQNSLEA 1000
    QKSSDTLTRH QPLLPLQCGE TDLDLTVQET GLQGPVGGDQ RPEVEDPEEL 1050
    SPALVVSSSQ SFVISGGGST VTENVVNS 1078
    Length:1,078
    Mass (Da):120,674
    Last modified:November 1, 1995 - v2
    Checksum:i620C57DB1A83E1DB
    GO
    Isoform 2 (identifier: P41180-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         536-536: E → EPLTFVLSVLQ

    Show »
    Length:1,088
    Mass (Da):121,772
    Checksum:i0D916FB23151762A
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti857 – 8571I → T in BAA09453. (PubMed:7677761)Curated
    Sequence conflicti878 – 8781A → R in BAA09453. (PubMed:7677761)Curated
    Sequence conflicti926 – 9261Q → R in AAA86503. (PubMed:7759551)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti11 – 111L → S in HHC1; demonstrates reduced intracellular and plasma membrane expression and signaling to the MAPK pathway in response to extracellular calcium relative to wild-type; fails to be inserted in the microsomes and does not undergo proper glycosylation. 1 Publication
    VAR_058046
    Natural varianti13 – 131L → P in HHC1; has a dose-response curve shifted to the right relative to that of wild-type; demonstrates reduced intracellular and plasma membrane expression and signaling to the MAPK pathway in response to extracellular calcium relative to wild-type; fails to be inserted in the microsomes and does not undergo proper glycosylation. 2 Publications
    VAR_058047
    Natural varianti14 – 141T → A Does not demonstrate reduced intracellular and plasma membrane expression and signaling to the MAPK pathway in response to extracellular calcium relative to wild-type; does not fail to be inserted in the microsomes and does undergo proper glycosylation. 1 Publication
    VAR_058048
    Natural varianti21 – 211G → R in HHC1. 1 Publication
    VAR_058049
    Natural varianti27 – 271Q → R Found in a patient with primary hyperparathyroidism detected at adulthood; mutant CASR is activated by a higher calcium concentrations than the wild-type. 1 Publication
    VAR_065198
    Natural varianti39 – 391P → A in HHC1. 1 Publication
    VAR_003585
    Natural varianti47 – 471K → N in HYPOC1; the EC(50) of the mutant is significantly lower than that of wild-type. 1 Publication
    VAR_058050
    Natural varianti62 – 621R → M in HHC1 and NSHPT; mild. 1 Publication
    VAR_003586
    Natural varianti66 – 661R → C in HHC1. 1 Publication
    VAR_003587
    Natural varianti100 – 1001T → I Found in a patient with primary hyperparathyroidism detected at adulthood. 1 Publication
    VAR_065199
    Natural varianti116 – 1161A → T in HYPOC1. 1 Publication
    VAR_003588
    Natural varianti118 – 1181N → K in HYPOC1; the mutation shifts the concentration-response curve to the left and increases maximal activity. 2 Publications
    VAR_058051
    Natural varianti125 – 1251L → P in HYPOC1; shifts the concentration-response curve of calcium ions to the left. 1 Publication
    VAR_058052
    Natural varianti127 – 1271E → A in HYPOC1. 1 Publication
    VAR_003589
    Natural varianti128 – 1281F → L in HYPOC1; there is a shift in the dose-response curve so that the extracellular calcium concentration needed to produce half-maximal increase in total inositol phosphate in the cells is significantly lower than the one required for the wild-type receptor. 1 Publication
    VAR_058053
    Natural varianti131 – 1311C → W in HYPOC1; associated with clinical features of Bartter syndrome. 1 Publication
    VAR_058054
    Natural varianti138 – 1381T → M in HHC1. 1 Publication
    VAR_003590
    Natural varianti143 – 1431G → E in HHC1. 1 Publication
    VAR_003591
    Natural varianti151 – 1511T → M in HYPOC1; there is a shift in the dose-response curve so that the extracellular calcium concentration needed to produce half-maximal increase in total inositol phosphate in the cells is significantly lower than the one required for the wild-type receptor. 2 Publications
    VAR_058055
    Natural varianti171 – 1711S → N in HHC1. 1 Publication
    VAR_058056
    Natural varianti174 – 1741L → R in HHC1. 1 Publication
    VAR_003592
    Natural varianti180 – 1801F → C in HHC1; although the mutant receptor is expressed normally at the cell surface it is unresponsive with respect to intracellular signaling (MAPK activation) to increases in extracellular calcium concentrations. 1 Publication
    VAR_058057
    Natural varianti185 – 1851R → Q in HHC1. 1 Publication
    VAR_003593
    Natural varianti191 – 1911E → K in HYPOC1; there is a shift in the dose-response curve so that the extracellular calcium concentration needed to produce half-maximal increase in total inositol phosphate in the cells is significantly lower than the one required for the wild-type receptor. 1 Publication
    VAR_058058
    Natural varianti221 – 2211P → Q in HHC1. 1 Publication
    VAR_058059
    Natural varianti225 – 2251K → T in HHC1. 1 Publication
    VAR_058060
    Natural varianti227 – 2271R → L in NSHPT; impaired in their MAPK response to increasing extracellular calcium concentrations; more markedly impaired relative to wild-type then Gln-227; when cotransfected with wild-type the curve is right-shifted intermediate to the curve for wild-type. 1 Publication
    Corresponds to variant rs28936684 [ dbSNP | Ensembl ].
    VAR_003594
    Natural varianti227 – 2271R → Q in HHC1; impaired in their MAPK response to increasing extracellular calcium concentrations; less markedly impaired relative to wild-type then Leu-227; when cotransfected with wild-type the curve is right-shifted intermediate to the curve for wild-type. 2 Publications
    VAR_003595
    Natural varianti250 – 2501E → K.1 Publication
    Corresponds to variant rs62269092 [ dbSNP | Ensembl ].
    VAR_058061
    Natural varianti271 – 2711S → F in HHC1. 1 Publication
    VAR_058062
    Natural varianti297 – 2971E → K in HHC1 and NSHPT. 1 Publication
    VAR_003596
    Natural varianti336 – 3361Missing Found in a patient with primary hyperparathyroidism detected at adulthood. 1 Publication
    VAR_065200
    Natural varianti339 – 3391P → T Mutation found in a patient with primary hyperparathyroidism detected at adulthood; inactivating mutation; mutant CASR is activated by a higher calcium concentrations than the wild-type. 1 Publication
    VAR_065201
    Natural varianti354 – 3541E → A in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication
    VAR_060206
    Natural varianti397 – 3971G → R in HHC1. 1 Publication
    VAR_058063
    Natural varianti465 – 4651R → Q in HHC1; loss-of-function mutation; the quantity of the mutant receptor is higher than that of the wild-type receptor; dose-response curves show that the mutation significantly reduces the sensitivity of the receptor to extracellular calcium concentrations. 1 Publication
    VAR_058064
    Natural varianti509 – 5091G → R in HHC1. 1 Publication
    Corresponds to variant rs193922423 [ dbSNP | Ensembl ].
    VAR_058065
    Natural varianti553 – 5531G → R in HHC1. 1 Publication
    VAR_058066
    Natural varianti555 – 5551I → V in HHC1. 1 Publication
    VAR_058067
    Natural varianti557 – 5571G → E in HHC1. 1 Publication
    VAR_012649
    Natural varianti562 – 5621C → Y in HHC1. 1 Publication
    VAR_058068
    Natural varianti582 – 5821C → F in HHC1. 1 Publication
    VAR_058069
    Natural varianti582 – 5821C → Y in NSHPT. 2 Publications
    VAR_003597
    Natural varianti604 – 6041E → K in HYPOC1; there is a significant leftward shift in the concentration response curves for the effects of extracellular calcium on both intracellular calcium mobilization and MAPK activity. 1 Publication
    VAR_058070
    Natural varianti612 – 6121F → S in HYPOC1. 1 Publication
    VAR_058071
    Natural varianti616 – 6161L → V in HYPOC1; does not affect the total accumulation of inositol phosphates as a function of extracellular calcium concentrations in transfected cells. 1 Publication
    VAR_015414
    Natural varianti623 – 6231G → D in HHC1. 1 Publication
    VAR_058072
    Natural varianti650 – 6501L → P Found in a patient with primary hyperparathyroidism detected at adulthood. 1 Publication
    VAR_065202
    Natural varianti670 – 6701G → E in NSHPT. 1 Publication
    VAR_058073
    Natural varianti670 – 6701G → R in HHC1. 1 Publication
    VAR_058074
    Natural varianti681 – 6811Q → H in HYPOC1. 1 Publication
    VAR_003598
    Natural varianti686 – 6861I → V in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication
    VAR_060207
    Natural varianti689 – 6891V → M Found in a patient with primary hyperparathyroidism detected at adulthood. 1 Publication
    VAR_065203
    Natural varianti697 – 6971V → M in HHC1. 1 Publication
    VAR_065494
    Natural varianti727 – 7271L → Q in HYPOC1; the mutant receptor demonstrates a significant leftward shift in the extracellular calcium/intracellular signaling dose-response curve versus that for the wild-type receptor. 1 Publication
    VAR_058075
    Natural varianti728 – 7281V → F in HHC1. 1 Publication
    VAR_058076
    Natural varianti742 – 7421W → R in HHC1. 1 Publication
    VAR_058077
    Natural varianti767 – 7671E → K in HYPOC1. 1 Publication
    VAR_021019
    Natural varianti773 – 7731L → R in HYPOC1; the mutation shifts the concentration-response curve to the left and increases maximal activity. 1 Publication
    VAR_058078
    Natural varianti788 – 7881F → C in HYPOC1; leftward shift in the concentration-response curve for the mutant receptor; cells cotransfected with both the wild-type and the mutant receptor show an EC(50) similar to the mutant; a gain-of-function mutation rendering the receptor more sensitive than normal to activation. 1 Publication
    VAR_058079
    Natural varianti788 – 7881F → L in HYPOC1; induces a significant shift to the left relative to the wild-type protein in the MAPK response to increasing extracellular calcium concentrations. 1 Publication
    VAR_058080
    Natural varianti795 – 7951R → W in HHC1. 1 Publication
    VAR_003599
    Natural varianti806 – 8061F → S in HYPOC1; does not produce a significant activating effect; decreased cell surface receptor expression. 2 Publications
    VAR_003600
    Natural varianti820 – 8201S → F in HYPOC1; the concentration-response curve of the mutant receptor is left-shifted and its EC(50) is significantly lower than that of the wild-type. 1 Publication
    VAR_058081
    Natural varianti843 – 8431A → E in HYPOC1; also in HYPOC1 associated with clinical features of Bartter syndrome; shifts the concentration-response curve of calcium ions to the left. 2 Publications
    VAR_058082
    Natural varianti851 – 8511C → S.1 Publication
    VAR_003601
    Natural varianti881 – 8811F → L Probable disease-associated mutation found in a patient with hypercalciuric hypercalcemia; mutant CASR has a right-shifted dose-response to extracellular calcium concentrations; activated by a higher calcium concentrations than the wild-type. 1 Publication
    VAR_058083
    Natural varianti886 – 8861R → W in HHC1. 1 Publication
    VAR_058084
    Natural varianti898 – 8981R → Q in EIG8. 1 Publication
    VAR_060208
    Natural varianti951 – 9511P → T.
    Corresponds to variant rs4987051 [ dbSNP | Ensembl ].
    VAR_020220
    Natural varianti986 – 9861A → S Associated with high serum level of calcium; is also a potential predisposing factor in disorders of bone and mineral metabolism. 8 Publications
    Corresponds to variant rs1801725 [ dbSNP | Ensembl ].
    VAR_014450
    Natural varianti988 – 9881A → G in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication
    VAR_060209
    Natural varianti988 – 9881A → V in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication
    VAR_060210
    Natural varianti990 – 9901R → G Associated with low serum level of calcium. 8 Publications
    Corresponds to variant rs1042636 [ dbSNP | Ensembl ].
    VAR_020221
    Natural varianti1011 – 10111Q → E Associated with high serum level of calcium. 4 Publications
    Corresponds to variant rs1801726 [ dbSNP | Ensembl ].
    VAR_014451

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei536 – 5361E → EPLTFVLSVLQ in isoform 2. 1 PublicationVSP_002035

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X81086 Genomic DNA. Translation: CAA56990.1.
    U20759 mRNA. Translation: AAA86503.1.
    U20760 mRNA. Translation: AAA86504.1.
    D50855 mRNA. Translation: BAA09453.1.
    S83176 mRNA. Translation: AAB46873.1.
    S79217 mRNA. Translation: AAB35262.2.
    S81755 mRNA. Translation: AAD14370.1.
    S68032 Genomic DNA. Translation: AAB29413.2. Sequence problems.
    S68033 Genomic DNA. Translation: AAB29414.1.
    S68036 Genomic DNA. Translation: AAB29415.1.
    DQ088967 Genomic DNA. Translation: AAY68221.1.
    BC104999 mRNA. Translation: AAI05000.1.
    BC112236 mRNA. Translation: AAI12237.1.
    CCDSiCCDS3010.1. [P41180-1]
    CCDS54632.1. [P41180-2]
    PIRiA56715.
    B56715.
    RefSeqiNP_000379.2. NM_000388.3. [P41180-1]
    NP_001171536.1. NM_001178065.1. [P41180-2]
    UniGeneiHs.435615.

    Genome annotation databases

    EnsembliENST00000296154; ENSP00000296154; ENSG00000036828.
    ENST00000490131; ENSP00000418685; ENSG00000036828.
    GeneIDi846.
    KEGGihsa:846.
    UCSCiuc003eev.4. human. [P41180-1]
    uc003eew.4. human. [P41180-2]

    Polymorphism databases

    DMDMi1168781.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X81086 Genomic DNA. Translation: CAA56990.1 .
    U20759 mRNA. Translation: AAA86503.1 .
    U20760 mRNA. Translation: AAA86504.1 .
    D50855 mRNA. Translation: BAA09453.1 .
    S83176 mRNA. Translation: AAB46873.1 .
    S79217 mRNA. Translation: AAB35262.2 .
    S81755 mRNA. Translation: AAD14370.1 .
    S68032 Genomic DNA. Translation: AAB29413.2 . Sequence problems.
    S68033 Genomic DNA. Translation: AAB29414.1 .
    S68036 Genomic DNA. Translation: AAB29415.1 .
    DQ088967 Genomic DNA. Translation: AAY68221.1 .
    BC104999 mRNA. Translation: AAI05000.1 .
    BC112236 mRNA. Translation: AAI12237.1 .
    CCDSi CCDS3010.1. [P41180-1 ]
    CCDS54632.1. [P41180-2 ]
    PIRi A56715.
    B56715.
    RefSeqi NP_000379.2. NM_000388.3. [P41180-1 ]
    NP_001171536.1. NM_001178065.1. [P41180-2 ]
    UniGenei Hs.435615.

    3D structure databases

    ProteinModelPortali P41180.
    SMRi P41180. Positions 26-493, 603-864.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107296. 10 interactions.
    DIPi DIP-5975N.
    IntActi P41180. 1 interaction.
    MINTi MINT-201342.
    STRINGi 9606.ENSP00000296154.

    Chemistry

    BindingDBi P41180.
    ChEMBLi CHEMBL1878.
    DrugBanki DB01012. Cinacalcet.
    GuidetoPHARMACOLOGYi 54.

    Protein family/group databases

    TCDBi 9.A.14.7.2. the g-protein-coupled receptor (gpcr) family.
    GPCRDBi Search...

    PTM databases

    PhosphoSitei P41180.

    Polymorphism databases

    DMDMi 1168781.

    Proteomic databases

    PaxDbi P41180.
    PRIDEi P41180.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000296154 ; ENSP00000296154 ; ENSG00000036828 .
    ENST00000490131 ; ENSP00000418685 ; ENSG00000036828 .
    GeneIDi 846.
    KEGGi hsa:846.
    UCSCi uc003eev.4. human. [P41180-1 ]
    uc003eew.4. human. [P41180-2 ]

    Organism-specific databases

    CTDi 846.
    GeneCardsi GC03P121820.
    H-InvDB HIX0163457.
    HGNCi HGNC:1514. CASR.
    HPAi HPA039686.
    MIMi 145980. phenotype.
    239200. phenotype.
    601198. phenotype.
    601199. gene+phenotype.
    612899. phenotype.
    neXtProti NX_P41180.
    Orphaneti 428. Autosomal dominant hypocalcemia.
    263417. Bartter syndrome with hypocalcemia.
    93372. Familial hypocalciuric hypercalcemia type 1.
    189466. Familial isolated hypoparathyroidism due to impaired PTH secretion.
    417. Neonatal severe primary hyperparathyroidism.
    PharmGKBi PA26097.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG295200.
    HOVERGENi HBG052876.
    KOi K04612.
    OrthoDBi EOG7DZ8J8.
    PhylomeDBi P41180.

    Enzyme and pathway databases

    Reactomei REACT_18283. G alpha (q) signalling events.
    REACT_18319. Class C/3 (Metabotropic glutamate/pheromone receptors).
    REACT_19231. G alpha (i) signalling events.

    Miscellaneous databases

    GeneWikii Calcium-sensing_receptor.
    GenomeRNAii 846.
    NextBioi 3546.
    PROi P41180.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P41180.
    Bgeei P41180.
    CleanExi HS_CASR.
    Genevestigatori P41180.

    Family and domain databases

    InterProi IPR001828. ANF_lig-bd_rcpt.
    IPR000337. GPCR_3.
    IPR011500. GPCR_3_9-Cys_dom.
    IPR017978. GPCR_3_C.
    IPR017979. GPCR_3_CS.
    IPR028082. Peripla_BP_I.
    [Graphical view ]
    Pfami PF00003. 7tm_3. 1 hit.
    PF01094. ANF_receptor. 1 hit.
    PF07562. NCD3G. 1 hit.
    [Graphical view ]
    PRINTSi PR00248. GPCRMGR.
    SUPFAMi SSF53822. SSF53822. 1 hit.
    PROSITEi PS00979. G_PROTEIN_RECEP_F3_1. 1 hit.
    PS00980. G_PROTEIN_RECEP_F3_2. 1 hit.
    PS00981. G_PROTEIN_RECEP_F3_3. 1 hit.
    PS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Pearce S.H.S., Thakker R.V.
      Submitted (DEC-1994) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs."
      Garrett J.E., Capuano I.V., Hammerland L.G., Hung B.C., Brown E.M., Hebert S.C., Nemeth E.F., Fuller F.
      J. Biol. Chem. 270:12919-12925(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT GLY-990.
      Tissue: Parathyroid.
    3. "Molecular cloning of a putative Ca(2+)-sensing receptor cDNA from human kidney."
      Aida K., Koishi S., Tawata M., Onaya T.
      Biochem. Biophys. Res. Commun. 214:524-529(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Kidney.
    4. "Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion."
      Freichel M., Zink-Lorenz A., Holloschi A., Hafner M., Flockerzi V., Raue F.
      Endocrinology 137:3842-3848(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    5. SeattleSNPs variation discovery resource
      Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-986; GLY-990 AND GLU-1011.
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain.
    7. "Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene."
      Aida K., Koishi S., Inoue M., Nakazato M., Tawata M., Onaya T.
      J. Clin. Endocrinol. Metab. 80:2594-2598(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-61, VARIANT HHC1 ALA-39.
    8. "Changes in calcium responsiveness and handling during keratinocyte differentiation. Potential role of the calcium receptor."
      Bikle D.D., Ratnam A., Mauro T., Harris J., Pillai S.
      J. Clin. Invest. 97:1085-1093(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 643-908.
    9. "Calcium-sensing receptor ubiquitination and degradation mediated by the E3 ubiquitin ligase dorfin."
      Huang Y., Niwa J., Sobue G., Breitwieser G.E.
      J. Biol. Chem. 281:11610-11617(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH VCP AND RNF19A, GLYCOSYLATION, UBIQUITINATION.
    10. "Rab1 small GTP-binding protein regulates cell surface trafficking of the human calcium-sensing receptor."
      Zhuang X., Adipietro K.A., Datta S., Northup J.K., Ray K.
      Endocrinology 151:5114-5123(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION.
    11. "Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism."
      Pollak M.R., Brown E.M., Chou Y.-H.W., Hebert S.C., Marx S.J., Steinmann B., Levi T., Seidman C.E., Seidman J.G.
      Cell 75:1297-1303(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HHC1 GLN-185; LYS-297 AND TRP-795.
    12. "Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation."
      Pollak M.R., Brown E.M., Estep H.L., McLaine P.N., Kifor O., Park J., Hebert S.C., Seidman C.E., Seidman J.G.
      Nat. Genet. 8:303-307(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HYPOC1 ALA-127.
    13. "Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia."
      Chou Y.-H.W., Pollak M.R., Brandi M.L., Toss G., Arnqvist H., Atkinson A.B., Papapoulos S.E., Marx S., Brown E.M., Seidman J.G., Seidman C.E.
      Am. J. Hum. Genet. 56:1075-1079(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HHC1 MET-62; CYS-66; MET-138; GLU-143 AND GLN-227.
    14. "Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism."
      Pearce S.H.S., Trump D., Wooding C., Besser G.M., Chew S.L., Grant D.B., Heath D.A., Hughes I.A., Paterson C.R., Whyte M.P., Thakker R.V.
      J. Clin. Invest. 96:2683-2692(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS NSHPT LEU-227 AND TYR-582.
    15. "The Ca(2+)-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism."
      Lovlie R., Eiken H.G., Sorheim J.I., Boman H.
      Hum. Genet. 98:129-133(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT FIH MET-151.
    16. "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism."
      Baron J., Winer K.K., Yanovski J.A., Cunningham A.W., Laue L., Zimmerman D., Cutler G.B. Jr.
      Hum. Mol. Genet. 5:601-606(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HYPOC1 THR-116; HIS-681 AND SER-806, VARIANT SER-851.
    17. "A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor."
      Pearce S.H.S., Williamson C., Kifor O., Bai M., Coulthard M.G., Davies M., Lewis-Barned N., McCredie D., Powell H., Kendall-Taylor P., Brown E.M., Thakker R.V.
      N. Engl. J. Med. 335:1115-1122(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612, CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191.
    18. "A novel mutation (L174R) in the Ca2+-sensing receptor gene associated with familial hypocalciuric hypercalcemia."
      Ward B.K., Stuckey B.G.A., Gutteridge D.H., Laing N.G., Pullan P.T., Ratajczak T.
      Hum. Mutat. 10:233-235(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHC1 ARG-174.
    19. "Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor."
      De Luca F., Ray K., Mancilla E.E., Fan G.-F., Winer K.K., Gore P., Spiegel A.M., Baron J.
      J. Clin. Endocrinol. Metab. 82:2710-2715(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806, CHARACTERIZATION OF VARIANTS HYPOC1 LYS-118; ARG-773 AND SER-806.
    20. "Two novel missense mutations in calcium-sensing receptor gene associated with neonatal severe hyperparathyroidism."
      Kobayashi M., Tanaka H., Tsuzuki K., Tsuyuki M., Igaki H., Ichinose Y., Aya K., Nishioka N., Seino Y.
      J. Clin. Endocrinol. Metab. 82:2716-2719(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT NSHPT GLU-670.
    21. "Familial hypoparathyroidism: identification of a novel gain of function mutation in transmembrane domain 5 of the calcium-sensing receptor."
      Watanabe T., Bai M., Lane C.R., Matsumoto S., Minamitani K., Minagawa M., Niimi H., Brown E.M., Yasuda T.
      J. Clin. Endocrinol. Metab. 83:2497-2502(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HYPOC1 CYS-788, CHARACTERIZATION OF VARIANT HYPOC1 CYS-788.
    22. "An adult patient with severe hypercalcaemia and hypocalciuria due to a novel homozygous inactivating mutation of calcium-sensing receptor."
      Chikatsu N., Fukumoto S., Suzawa M., Tanaka Y., Takeuchi Y., Takeda S., Tamura Y., Matsumoto T., Fujita T.
      Clin. Endocrinol. (Oxf.) 50:537-543(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ARG-27, CHARACTERIZATION OF VARIANT ARG-27, INVOLVEMENT IN PRIMARY HYPERPARATHYROIDISM.
    23. "A novel activating mutation in calcium-sensing receptor gene associated with a family of autosomal dominant hypocalcemia."
      Okazaki R., Chikatsu N., Nakatsu M., Takeuchi Y., Ajima M., Miki J., Fujita T., Arai M., Totsuka Y., Tanaka K., Fukumoto S.
      J. Clin. Endocrinol. Metab. 84:363-366(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HYPOC1 ASN-47, CHARACTERIZATION OF VARIANT HYPOC1 ASN-47.
    24. "Autosomal dominant hypoparathyroidism associated with short stature and premature osteoarthritis."
      Stock J.L., Brown R.S., Baron J., Coderre J.A., Mancilla E., De Luca F., Ray K., Mericq M.V.
      J. Clin. Endocrinol. Metab. 84:3036-3040(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HYPOC1 VAL-616, CHARACTERIZATION OF VARIANT HYPOC1 VAL-616.
    25. "A986S polymorphism of the calcium-sensing receptor and circulating calcium concentrations."
      Cole D.E.C., Peltekova V.D., Rubin L.A., Hawker G.A., Vieth R., Liew C.C., Hwang D.M., Evrovski J., Hendy G.N.
      Lancet 353:112-115(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT SER-986, ASSOCIATION WITH SERUM LEVEL OF CALCIUM.
    26. "Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor."
      Carling T., Szabo E., Bai M., Ridefelt P., Westin G., Gustavsson P., Trivedi S., Hellman P., Brown E.M., Dahl N., Rastad J.
      J. Clin. Endocrinol. Metab. 85:2042-2047(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HYPERCALCIURIC HYPERCALCEMIA LEU-881, CHARACTERIZATION OF VARIANT HYPERCALCIURIC HYPERCALCEMIA LEU-881.
    27. "A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia."
      Nakayama T., Minato M., Nakagawa M., Soma M., Tobe H., Aoi N., Kosuge K., Sato M., Ozawa Y., Kanmatsuse K., Kokubun S.
      Endocrine 15:277-282(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHC1 GLU-557.
    28. "Association between total serum calcium and the A986S polymorphism of the calcium-sensing receptor gene."
      Cole D.E.C., Vieth R., Trang H.M., Wong B.Y.-L., Hendy G.N., Rubin L.A.
      Mol. Genet. Metab. 72:168-174(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT SER-986, ASSOCIATION WITH SERUM LEVEL OF CALCIUM, PREDISPOSING FACTOR IN DISORDERS OF BONE AND MINERAL METABOLISM.
    29. "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., Murakami T., Tsukada T., Kitamura R., Chikatsu N., Takeo H., Takata N., Yasuda H., Fukumoto S., Tanaka Y., Nagata N., Yamaguchi K., Akatsu T., Yamamoto M.
      J. Clin. Endocrinol. Metab. 87:2681-2687(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HYPOC1 PHE-820, CHARACTERIZATION OF VARIANT HYPOC1 PHE-820, VARIANT GLY-990.
    30. "Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene."
      Sato K., Hasegawa Y., Nakae J., Nanao K., Takahashi I., Tajima T., Shinohara N., Fujieda K.
      J. Clin. Endocrinol. Metab. 87:3068-3073(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HYPOC1 PRO-125 AND GLU-843, CHARACTERIZATION OF VARIANTS HYPOC1 PRO-125 AND GLU-843.
    31. "Association between activating mutations of calcium-sensing receptor and Bartter's syndrome."
      Watanabe S., Fukumoto S., Chang H., Takeuchi Y., Hasegawa Y., Okazaki R., Chikatsu N., Fujita T.
      Lancet 360:692-694(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HYPOC1 TRP-131 AND GLU-843.
    32. "Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor."
      Tan Y.M., Cardinal J., Franks A.H., Mun H.-C., Lewis N., Harris L.B., Prins J.B., Conigrave A.D.
      J. Clin. Endocrinol. Metab. 88:605-610(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HYPOC1 LYS-604, CHARACTERIZATION OF VARIANT HYPOC1 LYS-604.
    33. "Recurrent familial hypocalcemia due to germline mosaicism for an activating mutation of the calcium-sensing receptor gene."
      Hendy G.N., Minutti C., Canaff L., Pidasheva S., Yang B., Nouhi Z., Zimmerman D., Wei C., Cole D.E.C.
      J. Clin. Endocrinol. Metab. 88:3674-3681(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HYPOC1 LEU-788, CHARACTERIZATION OF VARIANT HYPOC1 LEU-788.
    34. "Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor."
      Scillitani A., Guarnieri V., De Geronimo S., Muscarella L.A., Battista C., D'Agruma L., Bertoldo F., Florio C., Minisola S., Hendy G.N., Cole D.E.C.
      J. Clin. Endocrinol. Metab. 89:5634-5638(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS SER-986; GLY-990 AND GLU-1011, ASSOCIATION WITH SERUM LEVEL OF CALCIUM.
    35. "Severe hypercalcemia in a 9-year-old Brazilian girl due to a novel inactivating mutation of the calcium-sensing receptor."
      Miyashiro K., Kunii I., Manna T.D., de Menezes Filho H.C., Damiani D., Setian N., Hauache O.M.
      J. Clin. Endocrinol. Metab. 89:5936-5941(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHC1 PRO-13, CHARACTERIZATION OF VARIANT HHC1 PRO-13.
    36. "Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications."
      Warner J., Epstein M., Sweet A., Singh D., Burgess J., Stranks S., Hill P., Perry-Keene D., Learoyd D., Robinson B., Birdsey P., Mackenzie E., Teh B.T., Prins J.B., Cardinal J.
      J. Med. Genet. 41:155-160(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS ILE-100; LYS-336 DEL; PRO-650; MET-689; SER-986; GLY-990 AND GLU-1011, INVOLVEMENT IN PRIMARY HYPERPARATHYROIDISM.
    37. "A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia."
      Uckun-Kitapci A., Underwood L.E., Zhang J., Moats-Staats B.
      Am. J. Med. Genet. A 132:125-129(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HYPOC1 LYS-767, VARIANT GLY-990.
    38. "Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia."
      Pidasheva S., Canaff L., Simonds W.F., Marx S.J., Hendy G.N.
      Hum. Mol. Genet. 14:1679-1690(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HHC1 SER-11 AND PRO-13, VARIANT ALA-14, CHARACTERIZATION OF VARIANTS HHC1 SER-11 AND PRO-13, CHARACTERIZATION OF VARIANT ALA-14.
    39. "Functional characterization of calcium-sensing receptor codon 227 mutations presenting as either familial (benign) hypocalciuric hypercalcemia or neonatal hyperparathyroidism."
      Wystrychowski A., Pidasheva S., Canaff L., Chudek J., Kokot F., Wiecek A., Hendy G.N.
      J. Clin. Endocrinol. Metab. 90:864-870(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHC1 GLN-227, CHARACTERIZATION OF VARIANT NSHPT LEU-227, CHARACTERIZATION OF VARIANT HHC1 GLN-227.
    40. "Identification of a novel inactivating R465Q mutation of the calcium-sensing receptor."
      Leech C., Lohse P., Stanojevic V., Lechner A., Goeke B., Spitzweg C.
      Biochem. Biophys. Res. Commun. 342:996-1002(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHC1 GLN-465, CHARACTERIZATION OF VARIANT HHC1 GLN-465, VARIANT SER-986.
    41. "A hypocalcemic child with a novel activating mutation of the calcium-sensing receptor gene: successful treatment with recombinant human parathyroid hormone."
      Mittelman S.D., Hendy G.N., Fefferman R.A., Canaff L., Mosesova I., Cole D.E., Burkett L., Geffner M.E.
      J. Clin. Endocrinol. Metab. 91:2474-2479(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HYPOC1 GLN-727, CHARACTERIZATION OF VARIANT HYPOC1 GLN-727.
    42. "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., Vrbikova J., Canaff L., Pawelek P.D., Goltzman D., Hendy G.N.
      J. Clin. Endocrinol. Metab. 92:2616-2623(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHC1 CYS-180, CHARACTERIZATION OF VARIANT HHC1 CYS-180.
    43. "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., Christensen S.E., Heickendorff L., Brixen K., Mosekilde L.
      J. Clin. Endocrinol. Metab. 92:4373-4379(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886, VARIANTS LYS-250; SER-986; GLY-990 AND GLU-1011.
    44. "An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene."
      Kapoor A., Satishchandra P., Ratnapriya R., Reddy R., Kadandale J., Shankar S.K., Anand A.
      Ann. Neurol. 64:158-167(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988, VARIANTS SER-986 AND GLY-990, TISSUE SPECIFICITY.
    45. "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., Nesbit M.A., Christie P.T., Lissens W., Van der Schueren B., Bex M., Bouillon R., Thakker R.V.
      Clin. Endocrinol. (Oxf.) 73:715-722(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT THR-339, CHARACTERIZATION OF VARIANT THR-339, INVOLVEMENT IN PRIMARY HYPERPARATHYROIDISM.
    46. "Familial hypocalciuric hypercalcemia: new mutation in the CASR gene converting valine 697 to methionine."
      Aparicio Lopez C., Anton-Martin P., Gil-Fournier B., Ramiro-Leon S., Perez-Nanclares G., Perez de Nanclares G., Martinez Menendez B., Castano L.
      Eur. J. Pediatr. 171:147-150(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HHC1 MET-697.

    Entry informationi

    Entry nameiCASR_HUMAN
    AccessioniPrimary (citable) accession number: P41180
    Secondary accession number(s): Q13912
    , Q16108, Q16109, Q16110, Q16379, Q2M1T0, Q4PJ19
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 159 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3