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Protein

Mineralocorticoid receptor

Gene

Nr3c2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Binding sitei767SteroidBy similarity1
Binding sitei773SteroidBy similarity1
Binding sitei814SteroidBy similarity1
Binding sitei942SteroidBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi604 – 669Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
Zinc fingeri604 – 624NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri640 – 664NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandLipid-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3094 Nr3c2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi643R → D: Lowers homodimerization and decreases receptor activity. 1 Publication1
Mutagenesisi645D → R: Lowers homodimerization and decreases receptor activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3507
GuidetoPHARMACOLOGYi626

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536851 – 981Mineralocorticoid receptorAdd BLAST981

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei250PhosphoserineBy similarity1
Modified residuei259PhosphoserineBy similarity1
Modified residuei283PhosphoserineCombined sources1
Modified residuei287PhosphoserineCombined sources1
Modified residuei299PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP22199
PRIDEiP22199

PTM databases

iPTMnetiP22199
PhosphoSitePlusiP22199

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-protein interaction databases

BioGridi247701, 1 interactor
STRINGi10116.ENSRNOP00000045942

Chemistry databases

BindingDBiP22199

Structurei

3D structure databases

ProteinModelPortaliP22199
SMRiP22199
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini723 – 961NR LBDPROSITE-ProRule annotationAdd BLAST239

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 603ModulatingAdd BLAST603
Regioni670 – 722HingeAdd BLAST53
Regioni779 – 782Important for coactivator bindingBy similarity4

Domaini

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

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri604 – 624NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri640 – 664NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
HOGENOMiHOG000247011
HOVERGENiHBG006336
InParanoidiP22199
KOiK08555
PhylomeDBiP22199

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F1M6V2F1M6V2_RAT
Mineralocorticoid receptor
Nr3c2
877Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti688E → K (PubMed:7982810).Curated1
Sequence conflicti771A → G (PubMed:7982810).Curated1
Sequence conflicti775I → S (PubMed:7982810).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003705634G → GKCSW in isoform 2. 1 Publication1
Alternative sequenceiVSP_007361783 – 807VLPGF…WMCLS → NLKTCLSRTKSPSSSILGCV YHRSL in isoform 3. CuratedAdd BLAST25
Alternative sequenceiVSP_007362808 – 981Missing in isoform 3. CuratedAdd BLAST174

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

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247701, 1 interactor
STRINGi10116.ENSRNOP00000045942

Chemistry databases

BindingDBiP22199
ChEMBLiCHEMBL3507
GuidetoPHARMACOLOGYi626

PTM databases

iPTMnetiP22199
PhosphoSitePlusiP22199

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

PROiPR:P22199

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMCR_RAT
AccessioniPrimary (citable) accession number: P22199
Secondary accession number(s): Q63763, Q64174
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: November 7, 2018
This is version 163 of the entry and version 1 of the sequence. See 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
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Main funding by: National Institutes of Health

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