MCR_MOUSE
ID MCR_MOUSE Reviewed; 978 AA.
AC Q8VII8; Q8VII9;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 30-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Mineralocorticoid receptor;
DE Short=MR;
DE AltName: Full=Nuclear receptor subfamily 3 group C member 2;
GN Name=Nr3c2; Synonyms=Mlr;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 5-109 AND 182-288.
RC STRAIN=C57BL/6 X DBA/2; TISSUE=Heart;
RX PubMed=11997477; DOI=10.1073/pnas.102673599;
RA Beggah A.T., Escoubet B., Puttini S., Cailmail S., Delage V.,
RA Ouvrard-Pascaud A., Bocchi B., Peuchmaur M., Delcayre C., Farman N.,
RA Jaisser F.;
RT "Reversible cardiac fibrosis and heart failure induced by conditional
RT expression of an antisense mRNA of the mineralocorticoid receptor in
RT cardiomyocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7160-7165(2002).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=19029984; DOI=10.1038/nm.1879;
RA Shibata S., Nagase M., Yoshida S., Kawarazaki W., Kurihara H., Tanaka H.,
RA Miyoshi J., Takai Y., Fujita T.;
RT "Modification of mineralocorticoid receptor function by Rac1 GTPase:
RT implication in proteinuric kidney disease.";
RL Nat. Med. 14:1370-1376(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250; SER-259; SER-283;
RP SER-287 AND SER-299, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Kidney, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Receptor for both mineralocorticoids (MC) such as aldosterone
CC and glucocorticoids (GC) such as corticosterone or cortisol. Binds to
CC mineralocorticoid response elements (MRE) and transactivates target
CC genes. The effect of MC is to increase ion and water transport and thus
CC raise extracellular fluid volume and blood pressure and lower potassium
CC levels. {ECO:0000269|PubMed:19029984}.
CC -!- SUBUNIT: Heteromultimeric cytoplasmic complex with HSP90, HSP70, and
CC FKBP4, in the absence of ligand. After ligand binding, it translocates
CC to the nucleus and binds to DNA as a homodimer and as a heterodimer
CC with NR3C1. Binds the coactivator NCOA2. May interact with HSD11B2 in
CC the absence of ligand. Binds the coactivators NCOA1, TIF1 and NRIP1 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus
CC {ECO:0000255|PROSITE-ProRule:PRU00407, ECO:0000269|PubMed:19029984}.
CC Endoplasmic reticulum membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Note=Cytoplasmic and nuclear in the absence of
CC ligand; nuclear after ligand-binding. When bound to HSD11B2, it is
CC found associated with the endoplasmic reticulum membrane (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in heart and kidney.
CC {ECO:0000269|PubMed:19029984}.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC subfamily. {ECO:0000305}.
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DR EMBL; AC113941; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC116768; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC118019; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC119248; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AJ311855; CAC86374.1; -; mRNA.
DR EMBL; AJ311856; CAC86375.1; -; mRNA.
DR AlphaFoldDB; Q8VII8; -.
DR SMR; Q8VII8; -.
DR STRING; 10090.ENSMUSP00000105538; -.
DR iPTMnet; Q8VII8; -.
DR PhosphoSitePlus; Q8VII8; -.
DR MaxQB; Q8VII8; -.
DR PaxDb; Q8VII8; -.
DR PRIDE; Q8VII8; -.
DR ProteomicsDB; 295717; -.
DR MGI; MGI:99459; Nr3c2.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; Q8VII8; -.
DR Reactome; R-MMU-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-MMU-4090294; SUMOylation of intracellular receptors.
DR ChiTaRS; Nr3c2; mouse.
DR PRO; PR:Q8VII8; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8VII8; protein.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; ISO:MGI.
DR GO; GO:0098831; C:presynaptic active zone cytoplasmic component; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0003707; F:nuclear steroid receptor activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0005496; F:steroid binding; IDA:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0038166; P:angiotensin-activated signaling pathway; IMP:MGI.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IMP:MGI.
DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; IBA:GO_Central.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0055075; P:potassium ion homeostasis; IMP:MGI.
DR GO; GO:0002017; P:regulation of blood volume by renal aldosterone; IMP:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0060078; P:regulation of postsynaptic membrane potential; IDA:SynGO.
DR GO; GO:1904451; P:regulation of potassium:proton exchanging ATPase activity; IDA:MGI.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IDA:SynGO.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0035812; P:renal sodium excretion; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; IMP:MGI.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; DNA-binding; Endoplasmic reticulum; Lipid-binding; Membrane;
KW Metal-binding; Nucleus; Phosphoprotein; Receptor; Reference proteome;
KW Steroid-binding; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..978
FT /note="Mineralocorticoid receptor"
FT /id="PRO_0000053683"
FT DOMAIN 720..958
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 603..666
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 603..623
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 637..661
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..602
FT /note="Modulating"
FT REGION 234..331
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 353..372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 667..719
FT /note="Hinge"
FT REGION 681..706
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 776..779
FT /note="Important for coactivator binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 686..700
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 603
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 606
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 620
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 623
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 637
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 643
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 653
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 656
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 764
FT /ligand="21-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:16973"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 764
FT /ligand="aldosterone"
FT /ligand_id="ChEBI:CHEBI:27584"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 764
FT /ligand="progesterone"
FT /ligand_id="ChEBI:CHEBI:17026"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 770
FT /ligand="21-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:16973"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 770
FT /ligand="aldosterone"
FT /ligand_id="ChEBI:CHEBI:27584"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 770
FT /ligand="progesterone"
FT /ligand_id="ChEBI:CHEBI:17026"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 811
FT /ligand="21-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:16973"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 811
FT /ligand="aldosterone"
FT /ligand_id="ChEBI:CHEBI:27584"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 811
FT /ligand="progesterone"
FT /ligand_id="ChEBI:CHEBI:17026"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 939
FT /ligand="21-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:16973"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 939
FT /ligand="aldosterone"
FT /ligand_id="ChEBI:CHEBI:27584"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 939
FT /ligand="progesterone"
FT /ligand_id="ChEBI:CHEBI:17026"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT CONFLICT 103
FT /note="E -> Q (in Ref. 2; CAC86374)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="G -> D (in Ref. 2; CAC86374)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 978 AA; 106447 MW; 4D6F2C870FB4050A CRC64;
METKGYHSLP EGLDMERRWS QVSQTLERSS LGPAERTNEN SYMEIVNVSC VSGATPNNST
QGSSKEKHEL LPCLQQDNSR SGILPSDIKT ELESKELSAT VAESMGLYMD SVRDAEYTYD
QQNQQGSLSP AKIYQNMEQL VKFYKENGHR SSTLSAISRP LRSFMPDSGT SMNGGALRAI
VKSPIICHEK SPSVCSPLNM PSSVCSPAGI NSMSSSTASF GSFPVHSPIT QGTSLTCSPS
VENRGSRSHS PVHASNVGSP LSSPLSSMKS PISSPPSHCS VKSPVSSPNN VPLRSSVSSP
ANLNNSRCSV SSPSNTNNRS TLSSPTASTV GSIGSPISNA FSYTTSGASA GAGAIQDMVP
SPDTHEKGAH DVPFPKTEEV EKAISNGVTG QLNIVQYIKP EPDGAFSSSC LGGNNKINPS
SPFSVPIKQE SSKHSCSGAS FKGNPTVNPF PFMDGSYFSF MDDKDYYSLS GILGPPVPGF
DSSCEGSAFP GGIKQEPDDG SYFPETSIPS SAIIGVNSGG QSFHYRIGAQ GTISLSRSPR
DQSFQHLSSF PPVNALVESW KPHGDLSSRR SDGYPVLEYI PENVSSSTLR SVSTGSSRPS
KICLVCGDEA SGCHYGVVTC GSCKVFFKRA VEHNYLCAGR NDCIIDKIRR KNCPACRLQK
CLQAGMNLGA RKSKKLGKLK GLHEEQPQQP PPPPPQSPEE GTTYIAPTKE PSVNSALVPQ
LASITRALTP SPSMILENIE PEIVYAGYDN SKPDTAESLL STLNRLAGKQ MIQVVKWAKV
LPGFKNLPLE DQITLIQYSW MCLSSFALSW RSYKHTNSQF LYFAPDLVFN EEKMHQSAMY
ELCQGMRQIS LQFVRLQLTF EEYSIMKVLL LLSTVPKDGL KSQAAFEEMR TNYIKELRKM
VTKCPNSSGQ SWQRFYQLTK LLDSMHDLVN DLLEFCFYTF RESQALKVEF PAMLVEIISD
QLPKVESGNA KPLYFHRK
