MCR_RAT
ID MCR_RAT Reviewed; 981 AA.
AC P22199; Q63763; Q64174;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 180.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RX PubMed=2558305; DOI=10.1210/mend-3-11-1877;
RA Patel P.D., Sherman T.G., Goldman D.J., Watson S.J.;
RT "Molecular cloning of a mineralocorticoid (type I) receptor complementary
RT DNA from rat hippocampus.";
RL Mol. Endocrinol. 3:1877-1885(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 597-679 (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=7495694; DOI=10.1016/0960-0760(95)00162-s;
RA Bloem L.J., Guo C., Pratt J.H.;
RT "Identification of a splice variant of the rat and human mineralocorticoid
RT receptor genes.";
RL J. Steroid Biochem. Mol. Biol. 55:159-162(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 688-787 (ISOFORM 1).
RC STRAIN=Wistar; TISSUE=Cochlea;
RX PubMed=7982810; DOI=10.1016/0378-5955(94)90023-x;
RA Furuta H., Mori N., Sato C., Hoshikawa H., Sakai S., Iwakura S., Doi K.;
RT "Mineralocorticoid type I receptor in the rat cochlea: mRNA identification
RT by polymerase chain reaction (PCR) and in situ hybridization.";
RL Hear. Res. 78:175-180(1994).
RN [4]
RP HOMODIMERIZATION, HETERODIMERIZATION WITH NR3C1, AND MUTAGENESIS OF ARG-643
RP AND ASP-645.
RX PubMed=8618925; DOI=10.1073/pnas.92.26.12480;
RA Liu W., Wang J., Sauter N.K., Pearce D.;
RT "Steroid receptor heterodimerization demonstrated in vitro and in vivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:12480-12484(1995).
RN [5]
RP INTERACTION WITH NCOA2.
RX PubMed=9111344; DOI=10.1128/mcb.17.5.2735;
RA Hong H., Kohli K., Garabedian M.J., Stallcup M.R.;
RT "GRIP1, a transcriptional coactivator for the AF-2 transactivation domain
RT of steroid, thyroid, retinoid, and vitamin D receptors.";
RL Mol. Cell. Biol. 17:2735-2744(1997).
RN [6]
RP PHOSPHORYLATION.
RX PubMed=9677313; DOI=10.1042/bj3330555;
RA Galigniana M.D.;
RT "Native rat kidney mineralocorticoid receptor is a phosphoprotein whose
RT transformation to a DNA-binding form is induced by phosphatases.";
RL Biochem. J. 333:555-563(1998).
RN [7]
RP IDENTIFICATION OF ISOFORM 3.
RX PubMed=10687858; DOI=10.1016/s0303-7207(99)00198-7;
RA Zhou M.-Y., Gomez-Sanchez C.E., Gomez-Sanchez E.P.;
RT "An alternatively spliced rat mineralocorticoid receptor mRNA causing
RT truncation of the steroid binding domain.";
RL Mol. Cell. Endocrinol. 159:125-131(2000).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283 AND SER-287, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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.
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}. Endoplasmic reticulum membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC Note=Cytoplasmic and nuclear in the absence of ligand; nuclear after
CC ligand-binding. When bound to HSD11B2, it is found associated with the
CC endoplasmic reticulum membrane (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P22199-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P22199-2; Sequence=VSP_003705;
CC Name=3;
CC IsoId=P22199-3; Sequence=VSP_007361, VSP_007362;
CC -!- TISSUE SPECIFICITY: Detected in liver, brain, heart, kidney, colon,
CC aorta, hippocampus, hypothalamus and adrenal fasciculata.
CC {ECO:0000269|PubMed:7495694}.
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:0000269|PubMed:9677313}.
CC -!- MISCELLANEOUS: [Isoform 3]: Very low transactivation activity, not
CC increased by aldosterone. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M36074; AAA41583.1; -; mRNA.
DR EMBL; S79920; AAB35738.1; -; mRNA.
DR EMBL; S75686; AAB32663.2; -; mRNA.
DR PIR; A41401; A41401.
DR RefSeq; NP_037263.1; NM_013131.1. [P22199-1]
DR AlphaFoldDB; P22199; -.
DR SMR; P22199; -.
DR BioGRID; 247701; 1.
DR STRING; 10116.ENSRNOP00000045942; -.
DR BindingDB; P22199; -.
DR ChEMBL; CHEMBL3507; -.
DR DrugCentral; P22199; -.
DR GuidetoPHARMACOLOGY; 626; -.
DR iPTMnet; P22199; -.
DR PhosphoSitePlus; P22199; -.
DR PaxDb; P22199; -.
DR PRIDE; P22199; -.
DR GeneID; 25672; -.
DR KEGG; rno:25672; -.
DR UCSC; RGD:3094; rat. [P22199-1]
DR CTD; 4306; -.
DR RGD; 3094; Nr3c2.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; P22199; -.
DR OrthoDB; 146963at2759; -.
DR PhylomeDB; P22199; -.
DR Reactome; R-RNO-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-RNO-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-RNO-4090294; SUMOylation of intracellular receptors.
DR PRO; PR:P22199; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; IDA:SynGO.
DR GO; GO:0098831; C:presynaptic active zone cytoplasmic component; IDA:SynGO.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:RGD.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0003707; F:nuclear steroid receptor activity; IMP:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
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; IDA:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0005496; F:steroid binding; IMP:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; ISO:RGD.
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:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0060078; P:regulation of postsynaptic membrane potential; ISO:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0035812; P:renal sodium excretion; ISO:RGD.
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 Alternative splicing; Cytoplasm; DNA-binding; Endoplasmic reticulum;
KW Lipid-binding; Membrane; Metal-binding; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Steroid-binding; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..981
FT /note="Mineralocorticoid receptor"
FT /id="PRO_0000053685"
FT DOMAIN 723..961
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 604..669
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 604..624
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 640..664
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..603
FT /note="Modulating"
FT REGION 234..331
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 355..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 670..722
FT /note="Hinge"
FT REGION 684..710
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 779..782
FT /note="Important for coactivator binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 689..703
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 604
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 607
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 621
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 624
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 640
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 646
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 659
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 767
FT /ligand="21-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:16973"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 767
FT /ligand="aldosterone"
FT /ligand_id="ChEBI:CHEBI:27584"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 767
FT /ligand="progesterone"
FT /ligand_id="ChEBI:CHEBI:17026"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 773
FT /ligand="21-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:16973"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 773
FT /ligand="aldosterone"
FT /ligand_id="ChEBI:CHEBI:27584"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 773
FT /ligand="progesterone"
FT /ligand_id="ChEBI:CHEBI:17026"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 814
FT /ligand="21-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:16973"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 814
FT /ligand="aldosterone"
FT /ligand_id="ChEBI:CHEBI:27584"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 814
FT /ligand="progesterone"
FT /ligand_id="ChEBI:CHEBI:17026"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 942
FT /ligand="21-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:16973"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 942
FT /ligand="aldosterone"
FT /ligand_id="ChEBI:CHEBI:27584"
FT /evidence="ECO:0000250|UniProtKB:P08235"
FT BINDING 942
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:0000250|UniProtKB:Q8VII8"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VII8"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VII8"
FT VAR_SEQ 634
FT /note="G -> GKCSW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7495694"
FT /id="VSP_003705"
FT VAR_SEQ 783..807
FT /note="VLPGFKNLPLEDQITLIQYSWMCLS -> NLKTCLSRTKSPSSSILGCVYHR
FT SL (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_007361"
FT VAR_SEQ 808..981
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_007362"
FT MUTAGEN 643
FT /note="R->D: Lowers homodimerization and decreases receptor
FT activity."
FT /evidence="ECO:0000269|PubMed:8618925"
FT MUTAGEN 645
FT /note="D->R: Lowers homodimerization and decreases receptor
FT activity."
FT /evidence="ECO:0000269|PubMed:8618925"
FT CONFLICT 688
FT /note="E -> K (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 771
FT /note="A -> G (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 775
FT /note="I -> S (in Ref. 3)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 981 AA; 106737 MW; 184F5D37C1B030F7 CRC64;
METKGYHSLP EGLDMERRWS QVSQTLERSS LGPAERTTEN NYMEIVNVSC VSGAIPNNST
QGSSKEKHEL LPYIQQDNSR SGILPSDIKT ELESKELSAT VAESMGLYMD SVRDAEYTYD
QQNQQGSLSP TKIYQNMEQL VKFYKENGHR SSTLSAMSRP LRSFMPDSAA SMNGGALRAI
VKSPIICHEK SSSVSSPLNM ASSVCSPVGI NSMSSSTTSF GSFPVHSPIT QGTSLTCSPS
VENRGSRSHS PTHASNVGSP LSSPLSSMKS PISSPPSHCS VKSPVSSPNN VPLRSSVSSP
ANLNNSRCSV SSPSNNTNNR STLSSPTAST VGSIGSPISN AFSYATSGAS AGAGAIQDVV
PSPDTHEKGA HDVPFPKTEE VEKAISNGVT GPLNIVQYIK SEPDGAFSSS CLGGNSKISP
SSPFSVPIKQ ESSKHSCSGA SFKGNPTVNP FPFMDGSYFS FMDDKDYYSL SGILGPPVPG
FDGSCEDSAF PVGIKQEPDD GSYYPEASIP SSAIVGVNSG GQSFHYRIGA QGTISLSRSP
RDQSFQHLSS FPPVNTLVES WKPHGDLSSR RSDGYPVLEY IPENVSSSTL RSVSTGSSRP
SKICLVCGDE ASGCHYGVVT CGSCKVFFKR AVEGQHNYLC AGRNDCIIDK IRRKNCPACR
LQKCLQAGMN LGARKSKKLG KLKGLHEEQP QQPPPPPPQS PEEGTTYIAP TKEPSVNSAL
VPQLTSITHA LTPSPAMILE NIEPETVYAG YDNSKPDTAE SLLSTLNRLA AKQMIQVVKW
AKVLPGFKNL PLEDQITLIQ YSWMCLSSFA LSWRSYKHTN SQLLYFAPDL VFNEEKMHQS
AMYELCQGMR QISLQFVRLQ LTFEEYSIMK VLLLLSTVPK DGLKSQAAFE EMRTNYIKEL
RKMVTKCPNS SGQSWQRFYQ LTKLLDSMHD LVSDLLEFCF YTFRESQALK VEFPAMLVEI
ITDQLPKVES GNAKPLYFHR K
