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Protein

Mineralocorticoid receptor

Gene

Nr3c2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei767 – 7671SteroidBy similarity
Binding sitei773 – 7731SteroidBy similarity
Binding sitei814 – 8141SteroidBy similarity
Binding sitei942 – 9421SteroidBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi604 – 66966Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri604 – 62421NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri640 – 66425NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • double-stranded DNA binding Source: RGD
  • hormone binding Source: RGD
  • mineralocorticoid receptor activity Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: RGD
  • sequence-specific DNA binding Source: RGD
  • steroid binding Source: RGD
  • steroid hormone receptor activity Source: RGD
  • transcription factor activity, sequence-specific DNA binding Source: RGD
  • zinc ion binding Source: InterPro

GO - Biological processi

  • mineralocorticoid receptor signaling pathway Source: RGD
  • regulation of cell proliferation Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Lipid-binding, Metal-binding, Steroid-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Mineralocorticoid receptor
Short name:
MR
Alternative name(s):
Nuclear receptor subfamily 3 group C member 2
Gene namesi
Name:Nr3c2
Synonyms:Mlr
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3094. Nr3c2.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus PROSITE-ProRule annotation
  • Endoplasmic reticulum membrane By similarity; Peripheral membrane protein By similarity

  • 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 (By similarity).By similarity

GO - Cellular componenti

  • cytoplasm Source: RGD
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi643 – 6431R → D: Lowers homodimerization and decreases receptor activity. 1 Publication
Mutagenesisi645 – 6451D → R: Lowers homodimerization and decreases receptor activity. 1 Publication

Chemistry

ChEMBLiCHEMBL3507.
GuidetoPHARMACOLOGYi626.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 981981Mineralocorticoid receptorPRO_0000053685Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei250 – 2501PhosphoserineBy similarity
Modified residuei259 – 2591PhosphoserineBy similarity
Modified residuei283 – 2831PhosphoserineCombined sources
Modified residuei287 – 2871PhosphoserineCombined sources
Modified residuei299 – 2991PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP22199.
PRIDEiP22199.

PTM databases

iPTMnetiP22199.
PhosphoSiteiP22199.

Expressioni

Tissue specificityi

Detected in liver, brain, heart, kidney, colon, aorta, hippocampus, hypothalamus and adrenal fasciculata.1 Publication

Interactioni

Subunit structurei

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. Binds the coactivator NCOA2. May interact with HSD11B2 in the absence of ligand. Binds the coactivators NCOA1, TIF1 and NRIP1 (By similarity).By similarity

GO - Molecular functioni

  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: RGD

Protein-protein interaction databases

BioGridi247701. 1 interaction.
MINTiMINT-6478722.
STRINGi10116.ENSRNOP00000045942.

Chemistry

BindingDBiP22199.

Structurei

3D structure databases

ProteinModelPortaliP22199.
SMRiP22199. Positions 599-678, 719-980.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 603603ModulatingAdd
BLAST
Regioni670 – 72960HingeAdd
BLAST
Regioni730 – 981252Steroid-bindingAdd
BLAST
Regioni779 – 7824Important for coactivator bindingBy similarity

Domaini

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri604 – 62421NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri640 – 66425NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000247011.
HOVERGENiHBG006336.
InParanoidiP22199.
KOiK08555.
PhylomeDBiP22199.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P22199-1) [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
METKGYHSLP EGLDMERRWS QVSQTLERSS LGPAERTTEN NYMEIVNVSC
60 70 80 90 100
VSGAIPNNST QGSSKEKHEL LPYIQQDNSR SGILPSDIKT ELESKELSAT
110 120 130 140 150
VAESMGLYMD SVRDAEYTYD QQNQQGSLSP TKIYQNMEQL VKFYKENGHR
160 170 180 190 200
SSTLSAMSRP LRSFMPDSAA SMNGGALRAI VKSPIICHEK SSSVSSPLNM
210 220 230 240 250
ASSVCSPVGI NSMSSSTTSF GSFPVHSPIT QGTSLTCSPS VENRGSRSHS
260 270 280 290 300
PTHASNVGSP LSSPLSSMKS PISSPPSHCS VKSPVSSPNN VPLRSSVSSP
310 320 330 340 350
ANLNNSRCSV SSPSNNTNNR STLSSPTAST VGSIGSPISN AFSYATSGAS
360 370 380 390 400
AGAGAIQDVV PSPDTHEKGA HDVPFPKTEE VEKAISNGVT GPLNIVQYIK
410 420 430 440 450
SEPDGAFSSS CLGGNSKISP SSPFSVPIKQ ESSKHSCSGA SFKGNPTVNP
460 470 480 490 500
FPFMDGSYFS FMDDKDYYSL SGILGPPVPG FDGSCEDSAF PVGIKQEPDD
510 520 530 540 550
GSYYPEASIP SSAIVGVNSG GQSFHYRIGA QGTISLSRSP RDQSFQHLSS
560 570 580 590 600
FPPVNTLVES WKPHGDLSSR RSDGYPVLEY IPENVSSSTL RSVSTGSSRP
610 620 630 640 650
SKICLVCGDE ASGCHYGVVT CGSCKVFFKR AVEGQHNYLC AGRNDCIIDK
660 670 680 690 700
IRRKNCPACR LQKCLQAGMN LGARKSKKLG KLKGLHEEQP QQPPPPPPQS
710 720 730 740 750
PEEGTTYIAP TKEPSVNSAL VPQLTSITHA LTPSPAMILE NIEPETVYAG
760 770 780 790 800
YDNSKPDTAE SLLSTLNRLA AKQMIQVVKW AKVLPGFKNL PLEDQITLIQ
810 820 830 840 850
YSWMCLSSFA LSWRSYKHTN SQLLYFAPDL VFNEEKMHQS AMYELCQGMR
860 870 880 890 900
QISLQFVRLQ LTFEEYSIMK VLLLLSTVPK DGLKSQAAFE EMRTNYIKEL
910 920 930 940 950
RKMVTKCPNS SGQSWQRFYQ LTKLLDSMHD LVSDLLEFCF YTFRESQALK
960 970 980
VEFPAMLVEI ITDQLPKVES GNAKPLYFHR K
Length:981
Mass (Da):106,737
Last modified:August 1, 1991 - v1
Checksum:i184F5D37C1B030F7
GO
Isoform 2 (identifier: P22199-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     634-634: G → GKCSW

Show »
Length:985
Mass (Da):107,242
Checksum:iF573341A5F29A2A2
GO
Isoform 3 (identifier: P22199-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     783-807: VLPGFKNLPLEDQITLIQYSWMCLS → NLKTCLSRTKSPSSSILGCVYHRSL
     808-981: Missing.

Note: Very low transactivation activity, not increased by aldosterone.
Show »
Length:807
Mass (Da):86,079
Checksum:i2C7C9C14AE4FBE5A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti688 – 6881E → K (PubMed:7982810).Curated
Sequence conflicti771 – 7711A → G (PubMed:7982810).Curated
Sequence conflicti775 – 7751I → S (PubMed:7982810).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei634 – 6341G → GKCSW in isoform 2. 1 PublicationVSP_003705
Alternative sequencei783 – 80725VLPGF…WMCLS → NLKTCLSRTKSPSSSILGCV YHRSL in isoform 3. CuratedVSP_007361Add
BLAST
Alternative sequencei808 – 981174Missing in isoform 3. CuratedVSP_007362Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M36074 mRNA. Translation: AAA41583.1.
S79920 mRNA. Translation: AAB35738.1.
S75686 mRNA. Translation: AAB32663.2.
PIRiA41401.
RefSeqiNP_037263.1. NM_013131.1. [P22199-1]
UniGeneiRn.9678.

Genome annotation databases

GeneIDi25672.
KEGGirno:25672.
UCSCiRGD:3094. rat. [P22199-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M36074 mRNA. Translation: AAA41583.1.
S79920 mRNA. Translation: AAB35738.1.
S75686 mRNA. Translation: AAB32663.2.
PIRiA41401.
RefSeqiNP_037263.1. NM_013131.1. [P22199-1]
UniGeneiRn.9678.

3D structure databases

ProteinModelPortaliP22199.
SMRiP22199. Positions 599-678, 719-980.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247701. 1 interaction.
MINTiMINT-6478722.
STRINGi10116.ENSRNOP00000045942.

Chemistry

BindingDBiP22199.
ChEMBLiCHEMBL3507.
GuidetoPHARMACOLOGYi626.

PTM databases

iPTMnetiP22199.
PhosphoSiteiP22199.

Proteomic databases

PaxDbiP22199.
PRIDEiP22199.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25672.
KEGGirno:25672.
UCSCiRGD:3094. rat. [P22199-1]

Organism-specific databases

CTDi4306.
RGDi3094. Nr3c2.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000247011.
HOVERGENiHBG006336.
InParanoidiP22199.
KOiK08555.
PhylomeDBiP22199.

Miscellaneous databases

PROiP22199.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of a mineralocorticoid (type I) receptor complementary DNA from rat hippocampus."
    Patel P.D., Sherman T.G., Goldman D.J., Watson S.J.
    Mol. Endocrinol. 3:1877-1885(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: Sprague-Dawley.
    Tissue: Hippocampus.
  2. "Identification of a splice variant of the rat and human mineralocorticoid receptor genes."
    Bloem L.J., Guo C., Pratt J.H.
    J. Steroid Biochem. Mol. Biol. 55:159-162(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 597-679 (ISOFORM 2), TISSUE SPECIFICITY.
    Tissue: Brain.
  3. "Mineralocorticoid type I receptor in the rat cochlea: mRNA identification by polymerase chain reaction (PCR) and in situ hybridization."
    Furuta H., Mori N., Sato C., Hoshikawa H., Sakai S., Iwakura S., Doi K.
    Hear. Res. 78:175-180(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 688-787 (ISOFORM 1).
    Strain: Wistar.
    Tissue: Cochlea.
  4. "Steroid receptor heterodimerization demonstrated in vitro and in vivo."
    Liu W., Wang J., Sauter N.K., Pearce D.
    Proc. Natl. Acad. Sci. U.S.A. 92:12480-12484(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: HOMODIMERIZATION, HETERODIMERIZATION WITH NR3C1, MUTAGENESIS OF ARG-643 AND ASP-645.
  5. "GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors."
    Hong H., Kohli K., Garabedian M.J., Stallcup M.R.
    Mol. Cell. Biol. 17:2735-2744(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NCOA2.
  6. "Native rat kidney mineralocorticoid receptor is a phosphoprotein whose transformation to a DNA-binding form is induced by phosphatases."
    Galigniana M.D.
    Biochem. J. 333:555-563(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.
  7. "An alternatively spliced rat mineralocorticoid receptor mRNA causing truncation of the steroid binding domain."
    Zhou M.-Y., Gomez-Sanchez C.E., Gomez-Sanchez E.P.
    Mol. Cell. Endocrinol. 159:125-131(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION OF ISOFORM 3.
  8. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283 AND SER-287, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiMCR_RAT
AccessioniPrimary (citable) accession number: P22199
Secondary accession number(s): Q63763, Q64174
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: June 8, 2016
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.