Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Extracellular calcium-sensing receptor

Gene

CASR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

  • G-protein coupled receptor activity Source: ProtInc
  • phosphatidylinositol phospholipase C activity Source: ProtInc

GO - Biological processi

  • anatomical structure morphogenesis Source: ProtInc
  • calcium ion import Source: UniProtKB
  • cellular calcium ion homeostasis Source: ProtInc
  • chemosensory behavior Source: ProtInc
  • detection of calcium ion Source: ProtInc
  • G-protein coupled receptor signaling pathway Source: ProtInc
  • ossification Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000036828-MONOMER.
ReactomeiR-HSA-416476. G alpha (q) signalling events.
R-HSA-418594. G alpha (i) signalling events.
R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).
SIGNORiP41180.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:1514. CASR.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 612ExtracellularSequence analysisAdd BLAST593
Transmembranei613 – 635Helical; Name=1Sequence analysisAdd BLAST23
Topological domaini636 – 649CytoplasmicSequence analysisAdd BLAST14
Transmembranei650 – 670Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini671 – 681ExtracellularSequence analysisAdd BLAST11
Transmembranei682 – 700Helical; Name=3Sequence analysisAdd BLAST19
Topological domaini701 – 724CytoplasmicSequence analysisAdd BLAST24
Transmembranei725 – 745Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini746 – 769ExtracellularSequence analysisAdd BLAST24
Transmembranei770 – 792Helical; Name=5Sequence analysisAdd BLAST23
Topological domaini793 – 805CytoplasmicSequence analysisAdd BLAST13
Transmembranei806 – 828Helical; Name=6Sequence analysisAdd BLAST23
Topological domaini829 – 836ExtracellularSequence analysis8
Transmembranei837 – 862Helical; Name=7Sequence analysisAdd BLAST26
Topological domaini863 – 1078CytoplasmicSequence analysisAdd BLAST216

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Hypocalciuric hypercalcemia, familial 1 (HHC1)12 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:145980
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05804611L → 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 Publication1
Natural variantiVAR_05804713L → 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 Publications1
Natural variantiVAR_05804921G → R in HHC1. 1 Publication1
Natural variantiVAR_00358539P → A in HHC1. 1 Publication1
Natural variantiVAR_00358662R → M in HHC1 and NSHPT; mild. 1 Publication1
Natural variantiVAR_00358766R → C in HHC1. 1 Publication1
Natural variantiVAR_003590138T → M in HHC1. 1 Publication1
Natural variantiVAR_003591143G → E in HHC1. 1 Publication1
Natural variantiVAR_058056171S → N in HHC1. 1 Publication1
Natural variantiVAR_003592174L → R in HHC1. 1 Publication1
Natural variantiVAR_058057180F → 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 Publication1
Natural variantiVAR_003593185R → Q in HHC1. 1 Publication1
Natural variantiVAR_058059221P → Q in HHC1. 1 Publication1
Natural variantiVAR_058060225K → T in HHC1. 1 Publication1
Natural variantiVAR_003595227R → Q in HHC1; impaired in their MAPK response to increasing extracellular calcium concentrations; less markedly impaired relative to wild-type than L-227; when cotransfected with wild-type the curve is right-shifted intermediate to the curve for wild-type. 2 Publications1
Natural variantiVAR_058062271S → F in HHC1. 1 Publication1
Natural variantiVAR_003596297E → K in HHC1 and NSHPT. 1 Publication1
Natural variantiVAR_058063397G → R in HHC1. 1 Publication1
Natural variantiVAR_058064465R → 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 Publication1
Natural variantiVAR_058065509G → R in HHC1. 1 PublicationCorresponds to variant rs193922423dbSNPEnsembl.1
Natural variantiVAR_058066553G → R in HHC1. 1 Publication1
Natural variantiVAR_058067555I → V in HHC1. 1 Publication1
Natural variantiVAR_012649557G → E in HHC1. 1 Publication1
Natural variantiVAR_058068562C → Y in HHC1. 1 Publication1
Natural variantiVAR_058069582C → F in HHC1. 1 Publication1
Natural variantiVAR_058072623G → D in HHC1. 1 Publication1
Natural variantiVAR_058074670G → R in HHC1. 1 Publication1
Natural variantiVAR_065494697V → M in HHC1. 1 Publication1
Natural variantiVAR_058076728V → F in HHC1. 1 Publication1
Natural variantiVAR_058077742W → R in HHC1. 1 Publication1
Natural variantiVAR_003599795R → W in HHC1. 1 Publication1
Natural variantiVAR_058084886R → W in HHC1. 1 Publication1
Hyperparathyroidism, neonatal severe (NSHPT)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:239200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00358662R → M in HHC1 and NSHPT; mild. 1 Publication1
Natural variantiVAR_003594227R → L in NSHPT; impaired in their MAPK response to increasing extracellular calcium concentrations; more markedly impaired relative to wild-type than Q-227; when cotransfected with wild-type the curve is right-shifted intermediate to the curve for wild-type. 2 PublicationsCorresponds to variant rs28936684dbSNPEnsembl.1
Natural variantiVAR_003596297E → K in HHC1 and NSHPT. 1 Publication1
Natural variantiVAR_003597582C → Y in NSHPT. 2 Publications1
Natural variantiVAR_058073670G → E in NSHPT. 1 Publication1
Hypocalcemia, autosomal dominant 1 (HYPOC1)14 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:601198
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05805047K → N in HYPOC1; the EC(50) of the mutant is significantly lower than that of wild-type. 1 Publication1
Natural variantiVAR_003588116A → T in HYPOC1. 1 Publication1
Natural variantiVAR_058051118N → K in HYPOC1; the mutation shifts the concentration-response curve to the left and increases maximal activity. 2 Publications1
Natural variantiVAR_058052125L → P in HYPOC1; shifts the concentration-response curve of calcium ions to the left. 1 Publication1
Natural variantiVAR_003589127E → A in HYPOC1. 1 Publication1
Natural variantiVAR_058053128F → 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 Publication1
Natural variantiVAR_058054131C → W in HYPOC1; associated with clinical features of Bartter syndrome. 1 Publication1
Natural variantiVAR_058055151T → 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 Publications1
Natural variantiVAR_058058191E → 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 Publication1
Natural variantiVAR_058070604E → 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 Publication1
Natural variantiVAR_058071612F → S in HYPOC1. 1 Publication1
Natural variantiVAR_015414616L → V in HYPOC1; does not affect the total accumulation of inositol phosphates as a function of extracellular calcium concentrations in transfected cells. 1 Publication1
Natural variantiVAR_003598681Q → H in HYPOC1. 1 Publication1
Natural variantiVAR_058075727L → 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 Publication1
Natural variantiVAR_021019767E → K in HYPOC1. 1 Publication1
Natural variantiVAR_058078773L → R in HYPOC1; the mutation shifts the concentration-response curve to the left and increases maximal activity. 1 Publication1
Natural variantiVAR_058079788F → 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 Publication1
Natural variantiVAR_058080788F → 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 Publication1
Natural variantiVAR_003600806F → S in HYPOC1; does not produce a significant activating effect; decreased cell surface receptor expression. 2 Publications1
Natural variantiVAR_058081820S → 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 Publication1
Natural variantiVAR_058082843A → 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 Publications1
Epilepsy, idiopathic generalized 8 (EIG8)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:612899
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_060206354E → A in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication1
Natural variantiVAR_060207686I → V in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication1
Natural variantiVAR_060208898R → Q in EIG8. 1 Publication1
Natural variantiVAR_060209988A → G in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication1
Natural variantiVAR_060210988A → V in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication1

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

DisGeNETi846.
MalaCardsiCASR.
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.

Chemistry databases

ChEMBLiCHEMBL1878.
DrugBankiDB01012. Cinacalcet.
GuidetoPHARMACOLOGYi54.

Polymorphism and mutation databases

BioMutaiCASR.
DMDMi1168781.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000001294620 – 1078Extracellular calcium-sensing receptorAdd BLAST1059

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi90N-linked (GlcNAc...)Sequence analysis1
Glycosylationi130N-linked (GlcNAc...)Sequence analysis1
Glycosylationi261N-linked (GlcNAc...)Sequence analysis1
Glycosylationi287N-linked (GlcNAc...)Sequence analysis1
Glycosylationi386N-linked (GlcNAc...)Sequence analysis1
Glycosylationi400N-linked (GlcNAc...)Sequence analysis1
Glycosylationi446N-linked (GlcNAc...)Sequence analysis1
Glycosylationi468N-linked (GlcNAc...)Sequence analysis1
Glycosylationi488N-linked (GlcNAc...)Sequence analysis1
Glycosylationi541N-linked (GlcNAc...)Sequence analysis1
Glycosylationi594N-linked (GlcNAc...)Sequence analysis1
Modified residuei920PhosphoserineBy similarity1
Modified residuei1061PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP41180.
PeptideAtlasiP41180.
PRIDEiP41180.

PTM databases

iPTMnetiP41180.
PhosphoSitePlusiP41180.

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

BgeeiENSG00000036828.
CleanExiHS_CASR.
GenevisibleiP41180. HS.

Organism-specific databases

HPAiHPA039686.
HPA050335.

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. 9 interactors.
DIPiDIP-5975N.
IntActiP41180. 1 interactor.
MINTiMINT-201342.
STRINGi9606.ENSP00000420194.

Chemistry databases

BindingDBiP41180.

Structurei

Secondary structure

11078
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 28Combined sources3
Beta strandi31 – 38Combined sources8
Beta strandi40 – 44Combined sources5
Beta strandi60 – 63Combined sources4
Helixi65 – 82Combined sources18
Beta strandi85 – 90Combined sources6
Beta strandi93 – 99Combined sources7
Helixi104 – 114Combined sources11
Helixi116 – 123Combined sources8
Helixi125 – 128Combined sources4
Beta strandi138 – 142Combined sources5
Helixi147 – 159Combined sources13
Beta strandi164 – 168Combined sources5
Helixi172 – 175Combined sources4
Turni177 – 179Combined sources3
Beta strandi183 – 187Combined sources5
Helixi191 – 203Combined sources13
Beta strandi208 – 216Combined sources9
Helixi219 – 232Combined sources14
Beta strandi237 – 243Combined sources7
Helixi249 – 261Combined sources13
Beta strandi266 – 270Combined sources5
Helixi273 – 285Combined sources13
Beta strandi292 – 295Combined sources4
Helixi297 – 300Combined sources4
Turni303 – 305Combined sources3
Helixi308 – 310Combined sources3
Helixi311 – 314Combined sources4
Beta strandi318 – 322Combined sources5
Helixi330 – 335Combined sources6
Turni339 – 341Combined sources3
Beta strandi343 – 345Combined sources3
Helixi348 – 356Combined sources9
Beta strandi358 – 360Combined sources3
Helixi374 – 378Combined sources5
Beta strandi384 – 386Combined sources3
Helixi387 – 389Combined sources3
Helixi401 – 403Combined sources3
Turni407 – 409Combined sources3
Helixi416 – 435Combined sources20
Beta strandi441 – 444Combined sources4
Helixi445 – 447Combined sources3
Helixi452 – 454Combined sources3
Helixi457 – 465Combined sources9
Beta strandi468 – 470Combined sources3
Beta strandi476 – 478Combined sources3
Beta strandi481 – 485Combined sources5
Beta strandi489 – 496Combined sources8
Turni498 – 500Combined sources3
Beta strandi502 – 511Combined sources10
Beta strandi513 – 515Combined sources3
Beta strandi519 – 523Combined sources5
Helixi525 – 527Combined sources3
Turni531 – 533Combined sources3
Beta strandi550 – 554Combined sources5
Beta strandi556 – 558Combined sources3
Beta strandi563 – 567Combined sources5
Beta strandi576 – 578Combined sources3
Beta strandi589 – 591Combined sources3
Beta strandi595 – 600Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5FBHX-ray2.70A/B20-541[»]
5FBKX-ray2.10A/B20-541[»]
5K5SX-ray2.60A/B20-607[»]
5K5TX-ray3.10A20-607[»]
ProteinModelPortaliP41180.
SMRiP41180.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni880 – 900Interaction with RNF19A1 PublicationAdd BLAST21

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1056. Eukaryota.
ENOG410XR6W. LUCA.
HOVERGENiHBG052876.
InParanoidiP41180.
KOiK04612.
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. AlignAdd to basket

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

        10         20         30         40         50
MAFYSCCWVL LALTWHTSAY GPDQRAQKKG DIILGGLFPI HFGVAAKDQD
60 70 80 90 100
LKSRPESVEC IRYNFRGFRW LQAMIFAIEE INSSPALLPN LTLGYRIFDT
110 120 130 140 150
CNTVSKALEA TLSFVAQNKI DSLNLDEFCN CSEHIPSTIA VVGATGSGVS
160 170 180 190 200
TAVANLLGLF YIPQVSYASS SRLLSNKNQF KSFLRTIPND EHQATAMADI
210 220 230 240 250
IEYFRWNWVG TIAADDDYGR PGIEKFREEA EERDICIDFS ELISQYSDEE
260 270 280 290 300
EIQHVVEVIQ NSTAKVIVVF SSGPDLEPLI KEIVRRNITG KIWLASEAWA
310 320 330 340 350
SSSLIAMPQY FHVVGGTIGF ALKAGQIPGF REFLKKVHPR KSVHNGFAKE
360 370 380 390 400
FWEETFNCHL QEGAKGPLPV DTFLRGHEES GDRFSNSSTA FRPLCTGDEN
410 420 430 440 450
ISSVETPYID YTHLRISYNV YLAVYSIAHA LQDIYTCLPG RGLFTNGSCA
460 470 480 490 500
DIKKVEAWQV LKHLRHLNFT NNMGEQVTFD ECGDLVGNYS IINWHLSPED
510 520 530 540 550
GSIVFKEVGY YNVYAKKGER LFINEEKILW SGFSREVPFS NCSRDCLAGT
560 570 580 590 600
RKGIIEGEPT CCFECVECPD GEYSDETDAS ACNKCPDDFW SNENHTSCIA
610 620 630 640 650
KEIEFLSWTE PFGIALTLFA VLGIFLTAFV LGVFIKFRNT PIVKATNREL
660 670 680 690 700
SYLLLFSLLC CFSSSLFFIG EPQDWTCRLR QPAFGISFVL CISCILVKTN
710 720 730 740 750
RVLLVFEAKI PTSFHRKWWG LNLQFLLVFL CTFMQIVICV IWLYTAPPSS
760 770 780 790 800
YRNQELEDEI IFITCHEGSL MALGFLIGYT CLLAAICFFF AFKSRKLPEN
810 820 830 840 850
FNEAKFITFS MLIFFIVWIS FIPAYASTYG KFVSAVEVIA ILAASFGLLA
860 870 880 890 900
CIFFNKIYII LFKPSRNTIE EVRCSTAAHA FKVAARATLR RSNVSRKRSS
910 920 930 940 950
SLGGSTGSTP SSSISSKSNS EDPFPQPERQ KQQQPLALTQ QEQQQQPLTL
960 970 980 990 1000
PQQQRSQQQP RCKQKVIFGS GTVTFSLSFD EPQKNAMAHR NSTHQNSLEA
1010 1020 1030 1040 1050
QKSSDTLTRH QPLLPLQCGE TDLDLTVQET GLQGPVGGDQ RPEVEDPEEL
1060 1070
SPALVVSSSQ SFVISGGGST VTENVVNS
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)DescriptionActionsGraphical viewLength
Sequence conflicti857I → T in BAA09453 (PubMed:7677761).Curated1
Sequence conflicti878A → R in BAA09453 (PubMed:7677761).Curated1
Sequence conflicti926Q → R in AAA86503 (PubMed:7759551).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05804611L → 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 Publication1
Natural variantiVAR_05804713L → 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 Publications1
Natural variantiVAR_05804814T → 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 Publication1
Natural variantiVAR_05804921G → R in HHC1. 1 Publication1
Natural variantiVAR_06519827Q → 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 Publication1
Natural variantiVAR_00358539P → A in HHC1. 1 Publication1
Natural variantiVAR_05805047K → N in HYPOC1; the EC(50) of the mutant is significantly lower than that of wild-type. 1 Publication1
Natural variantiVAR_00358662R → M in HHC1 and NSHPT; mild. 1 Publication1
Natural variantiVAR_00358766R → C in HHC1. 1 Publication1
Natural variantiVAR_065199100T → I Found in a patient with primary hyperparathyroidism detected at adulthood. 1 Publication1
Natural variantiVAR_003588116A → T in HYPOC1. 1 Publication1
Natural variantiVAR_058051118N → K in HYPOC1; the mutation shifts the concentration-response curve to the left and increases maximal activity. 2 Publications1
Natural variantiVAR_058052125L → P in HYPOC1; shifts the concentration-response curve of calcium ions to the left. 1 Publication1
Natural variantiVAR_003589127E → A in HYPOC1. 1 Publication1
Natural variantiVAR_058053128F → 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 Publication1
Natural variantiVAR_058054131C → W in HYPOC1; associated with clinical features of Bartter syndrome. 1 Publication1
Natural variantiVAR_003590138T → M in HHC1. 1 Publication1
Natural variantiVAR_003591143G → E in HHC1. 1 Publication1
Natural variantiVAR_058055151T → 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 Publications1
Natural variantiVAR_058056171S → N in HHC1. 1 Publication1
Natural variantiVAR_003592174L → R in HHC1. 1 Publication1
Natural variantiVAR_058057180F → 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 Publication1
Natural variantiVAR_003593185R → Q in HHC1. 1 Publication1
Natural variantiVAR_058058191E → 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 Publication1
Natural variantiVAR_058059221P → Q in HHC1. 1 Publication1
Natural variantiVAR_058060225K → T in HHC1. 1 Publication1
Natural variantiVAR_003594227R → L in NSHPT; impaired in their MAPK response to increasing extracellular calcium concentrations; more markedly impaired relative to wild-type than Q-227; when cotransfected with wild-type the curve is right-shifted intermediate to the curve for wild-type. 2 PublicationsCorresponds to variant rs28936684dbSNPEnsembl.1
Natural variantiVAR_003595227R → Q in HHC1; impaired in their MAPK response to increasing extracellular calcium concentrations; less markedly impaired relative to wild-type than L-227; when cotransfected with wild-type the curve is right-shifted intermediate to the curve for wild-type. 2 Publications1
Natural variantiVAR_058061250E → K.1 PublicationCorresponds to variant rs62269092dbSNPEnsembl.1
Natural variantiVAR_058062271S → F in HHC1. 1 Publication1
Natural variantiVAR_003596297E → K in HHC1 and NSHPT. 1 Publication1
Natural variantiVAR_065200336Missing Found in a patient with primary hyperparathyroidism detected at adulthood. 1 Publication1
Natural variantiVAR_065201339P → 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 Publication1
Natural variantiVAR_060206354E → A in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication1
Natural variantiVAR_058063397G → R in HHC1. 1 Publication1
Natural variantiVAR_058064465R → 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 Publication1
Natural variantiVAR_058065509G → R in HHC1. 1 PublicationCorresponds to variant rs193922423dbSNPEnsembl.1
Natural variantiVAR_058066553G → R in HHC1. 1 Publication1
Natural variantiVAR_058067555I → V in HHC1. 1 Publication1
Natural variantiVAR_012649557G → E in HHC1. 1 Publication1
Natural variantiVAR_058068562C → Y in HHC1. 1 Publication1
Natural variantiVAR_058069582C → F in HHC1. 1 Publication1
Natural variantiVAR_003597582C → Y in NSHPT. 2 Publications1
Natural variantiVAR_058070604E → 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 Publication1
Natural variantiVAR_058071612F → S in HYPOC1. 1 Publication1
Natural variantiVAR_015414616L → V in HYPOC1; does not affect the total accumulation of inositol phosphates as a function of extracellular calcium concentrations in transfected cells. 1 Publication1
Natural variantiVAR_058072623G → D in HHC1. 1 Publication1
Natural variantiVAR_065202650L → P Found in a patient with primary hyperparathyroidism detected at adulthood. 1 Publication1
Natural variantiVAR_058073670G → E in NSHPT. 1 Publication1
Natural variantiVAR_058074670G → R in HHC1. 1 Publication1
Natural variantiVAR_003598681Q → H in HYPOC1. 1 Publication1
Natural variantiVAR_060207686I → V in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication1
Natural variantiVAR_065203689V → M Found in a patient with primary hyperparathyroidism detected at adulthood. 1 Publication1
Natural variantiVAR_065494697V → M in HHC1. 1 Publication1
Natural variantiVAR_058075727L → 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 Publication1
Natural variantiVAR_058076728V → F in HHC1. 1 Publication1
Natural variantiVAR_058077742W → R in HHC1. 1 Publication1
Natural variantiVAR_021019767E → K in HYPOC1. 1 Publication1
Natural variantiVAR_058078773L → R in HYPOC1; the mutation shifts the concentration-response curve to the left and increases maximal activity. 1 Publication1
Natural variantiVAR_058079788F → 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 Publication1
Natural variantiVAR_058080788F → 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 Publication1
Natural variantiVAR_003599795R → W in HHC1. 1 Publication1
Natural variantiVAR_003600806F → S in HYPOC1; does not produce a significant activating effect; decreased cell surface receptor expression. 2 Publications1
Natural variantiVAR_058081820S → 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 Publication1
Natural variantiVAR_058082843A → 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 Publications1
Natural variantiVAR_003601851C → S.1 Publication1
Natural variantiVAR_058083881F → 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 Publication1
Natural variantiVAR_058084886R → W in HHC1. 1 Publication1
Natural variantiVAR_060208898R → Q in EIG8. 1 Publication1
Natural variantiVAR_020220951P → T.Corresponds to variant rs4987051dbSNPEnsembl.1
Natural variantiVAR_014450986A → S Associated with high serum level of calcium; is also a potential predisposing factor in disorders of bone and mineral metabolism. 8 PublicationsCorresponds to variant rs1801725dbSNPEnsembl.1
Natural variantiVAR_060209988A → G in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication1
Natural variantiVAR_060210988A → V in EIG8; patients present juvenile myoclonus epilepsy. 1 Publication1
Natural variantiVAR_020221990R → G Associated with low serum level of calcium. 8 PublicationsCorresponds to variant rs1042636dbSNPEnsembl.1
Natural variantiVAR_0144511011Q → E Associated with high serum level of calcium. 4 PublicationsCorresponds to variant rs1801726dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002035536E → EPLTFVLSVLQ in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.5. human. [P41180-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5FBHX-ray2.70A/B20-541[»]
5FBKX-ray2.10A/B20-541[»]
5K5SX-ray2.60A/B20-607[»]
5K5TX-ray3.10A20-607[»]
ProteinModelPortaliP41180.
SMRiP41180.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107296. 9 interactors.
DIPiDIP-5975N.
IntActiP41180. 1 interactor.
MINTiMINT-201342.
STRINGi9606.ENSP00000420194.

Chemistry databases

BindingDBiP41180.
ChEMBLiCHEMBL1878.
DrugBankiDB01012. Cinacalcet.
GuidetoPHARMACOLOGYi54.

Protein family/group databases

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

PTM databases

iPTMnetiP41180.
PhosphoSitePlusiP41180.

Polymorphism and mutation databases

BioMutaiCASR.
DMDMi1168781.

Proteomic databases

PaxDbiP41180.
PeptideAtlasiP41180.
PRIDEiP41180.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296154; ENSP00000296154; ENSG00000036828.
ENST00000490131; ENSP00000418685; ENSG00000036828.
GeneIDi846.
KEGGihsa:846.
UCSCiuc003eev.5. human. [P41180-1]

Organism-specific databases

CTDi846.
DisGeNETi846.
GeneCardsiCASR.
H-InvDBHIX0163457.
HGNCiHGNC:1514. CASR.
HPAiHPA039686.
HPA050335.
MalaCardsiCASR.
MIMi145980. phenotype.
239200. phenotype.
601198. phenotype.
601199. gene+phenotype.
612899. phenotype.
neXtProtiNX_P41180.
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.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1056. Eukaryota.
ENOG410XR6W. LUCA.
HOVERGENiHBG052876.
InParanoidiP41180.
KOiK04612.
PhylomeDBiP41180.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000036828-MONOMER.
ReactomeiR-HSA-416476. G alpha (q) signalling events.
R-HSA-418594. G alpha (i) signalling events.
R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).
SIGNORiP41180.

Miscellaneous databases

GeneWikiiCalcium-sensing_receptor.
GenomeRNAii846.
PROiP41180.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000036828.
CleanExiHS_CASR.
GenevisibleiP41180. HS.

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]
ProtoNetiSearch...

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: November 30, 2016
This is version 179 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.