Human Gene NR3C2 (ENST00000625323.2) Description and Page Index
  Description: Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels. (from UniProt P08235)
RefSeq Summary (NM_000901): This gene encodes the mineralocorticoid receptor, which mediates aldosterone actions on salt and water balance within restricted target cells. The protein functions as a ligand-dependent transcription factor that binds to mineralocorticoid response elements in order to transactivate target genes. Mutations in this gene cause autosomal dominant pseudohypoaldosteronism type I, a disorder characterized by urinary salt wasting. Defects in this gene are also associated with early onset hypertension with severe exacerbation in pregnancy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009].
Gencode Transcript: ENST00000625323.2
Gencode Gene: ENSG00000151623.15
Transcript (Including UTRs)
   Position: hg38 chr4:148,078,765-148,442,520 Size: 363,756 Total Exon Count: 9 Strand: -
Coding Region
   Position: hg38 chr4:148,081,344-148,436,860 Size: 355,517 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr4:148,078,765-148,442,520)mRNA (may differ from genome)Protein (988 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblExonPrimerGeneCardsHGNCLynx
MGImyGene2neXtProtPubMedReactomeStanford SOURCE
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: MCR_HUMAN
DESCRIPTION: RecName: Full=Mineralocorticoid receptor; Short=MR; AltName: Full=Nuclear receptor subfamily 3 group C member 2;
FUNCTION: Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.
SUBUNIT: Heteromultimeric cytoplasmic complex with HSP90, HSP70, and FKBP4, in the absence of ligand. After ligand binding, it translocates to the nucleus and binds to DNA as a homodimer and as a heterodimer with NR3C1. May interact with HSD11B2 in the absence of ligand. Binds the coactivators NCOA1, NCOA2, TIF1 and NRIP1.
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Endoplasmic reticulum membrane; Peripheral membrane protein. Note=Cytoplasmic and nuclear in the absence of ligand; nuclear after ligand-binding. When bound to HSD11B2, it is found associated with the endoplasmic reticulum membrane.
TISSUE SPECIFICITY: Ubiquitous. Highly expressed in distal tubules, convoluted tubules and cortical collecting duct in kidney, and in sweat glands. Detected at lower levels in cardiomyocytes, in epidermis and in colon enterocytes.
DOMAIN: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
PTM: Phosphorylated.
DISEASE: Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:177735]. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.
DISEASE: Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:605115]. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.
SIMILARITY: Belongs to the nuclear hormone receptor family. NR3 subfamily.
SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/NR3C2ID44262ch4q31.html";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NR3C2";
WEB RESOURCE: Name=Wikipedia; Note=Mineralocorticoid receptor entry; URL="http://en.wikipedia.org/wiki/Mineralocorticoid_receptor";

-  MalaCards Disease Associations
  MalaCards Gene Search: NR3C2
Diseases sorted by gene-association score: pseudohypoaldosteronism type i, autosomal dominant* (1667), hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy* (1650), pseudohypoaldosteronism* (469), pseudohypoaldosteronism, type i* (217), apparent mineralocorticoid excess (18), conn's syndrome (18), hyperaldosteronism (15), aldosteronism, glucocorticoid-remediable (13), systolic heart failure (12), hypertensive heart disease (11), renal fibrosis (10), liddle syndrome (9), arthrogryposis, distal, type 3 (8), adrenal gland hyperfunction (8), congestive heart failure (8), central serous chorioretinopathy (7), glucocorticoid resistance (7), pseudohyperkalemia, familial, 2, due to red cell leak (7), renal tubular acidosis (6), anuria (6), bartter syndrome, type 2 (6), nephrosclerosis (6), adrenal cortex disease (5), adrenal gland disease (5), hypertension, essential (5), idiopathic edema (4), ocular hypertension (4), endocrine organ benign neoplasm (4), heart disease (3), myocardial infarction (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 7.70 RPKM in Thyroid
Total median expression: 160.96 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -172.20363-0.474 Picture PostScript Text
3' UTR -670.502579-0.260 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008946 - Nucl_hormone_rcpt_ligand-bd
IPR000536 - Nucl_hrmn_rcpt_lig-bd_core
IPR001628 - Znf_hrmn_rcpt
IPR013088 - Znf_NHR/GATA

Pfam Domains:
PF00104 - Ligand-binding domain of nuclear hormone receptor
PF00105 - Zinc finger, C4 type (two domains)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1Y9R
- X-ray MuPIT

1YA3
- X-ray MuPIT

2A3I
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2AA2 - X-ray MuPIT 2AA5 - X-ray MuPIT 2AA6 - X-ray MuPIT
2AA7 - X-ray MuPIT 2AAX - X-ray MuPIT 2AB2 - X-ray MuPIT
2ABI - X-ray MuPIT 2OAX - X-ray MuPIT 3VHU - X-ray MuPIT
3VHV - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P08235
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0003707 steroid hormone receptor activity
GO:0005496 steroid binding
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0008289 lipid binding
GO:0043565 sequence-specific DNA binding
GO:0046872 metal ion binding

Biological Process:
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0007165 signal transduction
GO:0043401 steroid hormone mediated signaling pathway

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005829 cytosol
GO:0016020 membrane
GO:0043235 receptor complex


-  Descriptions from all associated GenBank mRNAs
  M16801 - Human mineralocorticoid receptor mRNA (hMR), complete cds.
BC111758 - Homo sapiens nuclear receptor subfamily 3, group C, member 2, mRNA (cDNA clone MGC:133092 IMAGE:40027353), complete cds.
AK304318 - Homo sapiens cDNA FLJ61075 complete cds, highly similar to Mineralocorticoid receptor.
AJ315514 - Homo sapiens mRNA for mineralocorticoid receptor delta (MR gene).
AB209056 - Homo sapiens mRNA for nuclear receptor subfamily 3, group C, member 2 variant protein.
AB587357 - Synthetic construct DNA, clone: pF1KB0468, Homo sapiens NR3C2 gene for nuclear receptor subfamily 3, group C, member 2, without stop codon, in Flexi system.
JD384977 - Sequence 366001 from Patent EP1572962.
JD206447 - Sequence 187471 from Patent EP1572962.
JD304438 - Sequence 285462 from Patent EP1572962.
JD409595 - Sequence 390619 from Patent EP1572962.
JD285640 - Sequence 266664 from Patent EP1572962.
JD403532 - Sequence 384556 from Patent EP1572962.
JD237967 - Sequence 218991 from Patent EP1572962.
JD096016 - Sequence 77040 from Patent EP1572962.
JD197545 - Sequence 178569 from Patent EP1572962.
JD487796 - Sequence 468820 from Patent EP1572962.
JD250655 - Sequence 231679 from Patent EP1572962.
JD097887 - Sequence 78911 from Patent EP1572962.
JD290982 - Sequence 272006 from Patent EP1572962.
JD298630 - Sequence 279654 from Patent EP1572962.
JD501469 - Sequence 482493 from Patent EP1572962.
JD101128 - Sequence 82152 from Patent EP1572962.
JD114873 - Sequence 95897 from Patent EP1572962.
JD448992 - Sequence 430016 from Patent EP1572962.
JD341245 - Sequence 322269 from Patent EP1572962.
JD562635 - Sequence 543659 from Patent EP1572962.
JD460681 - Sequence 441705 from Patent EP1572962.
JD246151 - Sequence 227175 from Patent EP1572962.
JD270376 - Sequence 251400 from Patent EP1572962.
JD056312 - Sequence 37336 from Patent EP1572962.
AJ315515 - Homo sapiens partial mRNA for putative mineralocorticoid receptor delta (MR gene).
AK123047 - Homo sapiens cDNA FLJ41052 fis, clone SMINT2006648.
MA870710 - JP 2018536436-A/2546: COMPOSITIONS AND METHODS FOR IMMUNOONCOLOGY.
LY593122 - KR 1020180133840-A/2546: COMPOSITIONS AND METHODS FOR IMMUNOONCOLOGY.
JD414137 - Sequence 395161 from Patent EP1572962.
JD177407 - Sequence 158431 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04960 - Aldosterone-regulated sodium reabsorption

Reactome (by CSHL, EBI, and GO)

Protein P08235 (Reactome details) participates in the following event(s):

R-HSA-376419 Formation of NR-MED1 Coactivator Complex
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-212436 Generic Transcription Pathway
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)
R-HSA-376419 Formation of NR-MED1 Coactivator Complex
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-212436 Generic Transcription Pathway
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)
R-HSA-376419 Formation of NR-MED1 Coactivator Complex
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-212436 Generic Transcription Pathway
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)
R-HSA-376419 Formation of NR-MED1 Coactivator Complex
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-212436 Generic Transcription Pathway
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)
R-HSA-5618099 SH binds SHR within the HSP90 chaperone complex
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-HSA-2262752 Cellular responses to stress
R-HSA-8953897 Cellular responses to external stimuli

-  Other Names for This Gene
  Alternate Gene Symbols: M16801, MCR, MCR_HUMAN, MLR, P08235, Q96KQ8, Q96KQ9, uc063act.1
UCSC ID: uc063act.1
RefSeq Accession: NM_000901
Protein: P08235 (aka MCR_HUMAN)
CCDS: CCDS3772.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.