Reviewed, UniProtKB/Swiss-Prot P08235 (MCR_HUMAN)

Names and origin

Protein names

Recommended name:
    Mineralocorticoid receptor
      Short name=MR
Alternative name(s):
    Nuclear receptor subfamily 3 group C member 2

Gene names

Name:	NR3C2
Synonyms:	MCR, MLR

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	984 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

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. Ref.1
Subunit structure	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. Ref.14
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. Ref.5 Ref.12
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. Ref.2 Ref.7
Domain	Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal steroid-binding domain.
Post-translational modification	Phosphorylated. Ref.5
Involvement in disease	Defects in NR3C2 are a cause of autosomal dominant pseudohypoaldosteronism type I (PHA1) [MIM:177735]. PHA1 is characterized by urinary salt wasting, resulting from target organ unresponsiveness to mineralocorticoids. There are 2 forms of PHA1: the autosomal dominant form that is mild, and the recessive form which is more severe and due to defects in any of the epithelial sodium channel subunits. In autosomal dominant PHA1 the target organ defect is confined to kidney. Clinical expression can vary from asymptomatic to moderate. It may be severe at birth, but symptoms remit with age. Familial and sporadic cases have been reported. Ref.4 Ref.17 Ref.20 Ref.21 Ref.23 Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy [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. Ref.4
Sequence similarities	Belongs to the nuclear hormone receptor family. NR3 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Endoplasmic reticulum Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Zinc-finger
Ligand	DNA-binding Lipid-binding Metal-binding Steroid-binding Zinc
Molecular function	Receptor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro signal transduction Ref.1 Traceable author statement. Source: ProtInc transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-KW extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Ref.2 Inferred from physical interaction. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro steroid binding Inferred from electronic annotation. Source: UniProtKB-KW steroid hormone receptor activity Ref.4 Traceable author statement. Source: ProtInc transcription factor activity Ref.1 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: P08235-1)

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.

Isoform 2 (identifier: P08235-2)

The sequence of this isoform differs from the canonical sequence as follows:
     672-706: ARKSKKLGKLKGIHEEQPQQQQPPPPPPPPQSPEE → ERRCISLPCMNYARGCTKSAFSSFDCSSPLKNTPS
     707-984: Missing.

Note: Lacks steroid-binding activity and acts as ligand-independent transactivator.

Isoform 3 (identifier: P08235-3)

The sequence of this isoform differs from the canonical sequence as follows:
     633-633: G → GKCSW

Isoform 4 (identifier: P08235-4)

Also known as: Delta;

The sequence of this isoform differs from the canonical sequence as follows:
     672-788: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 984

984

Mineralocorticoid receptor

PRO_0000053682

Regions

DNA binding

603 – 668

66

Nuclear receptor

Zinc finger

603 – 623

21

NR C4-type

Zinc finger

639 – 663

25

NR C4-type

Region

1 – 602

602

Modulating

Region

669 – 732

64

Hinge

Region

733 – 984

252

Steroid-binding

Region

782 – 785

4

Important for coactivator binding

Sites

Binding site

770

1

Steroid

Binding site

776

1

Steroid

Binding site

817

1

Steroid

Binding site

945

1

Steroid

Natural variations

Alternative sequence

633

1

G → GKCSW in isoform 3.

VSP_007357

Alternative sequence

672 – 788

117

Missing in isoform 4.

VSP_007360

Alternative sequence

672 – 706

35

ARKSK…QSPEE → ERRCISLPCMNYARGCTKSA FSSFDCSSPLKNTPS in isoform 2.

VSP_007358

Alternative sequence

707 – 984

278

Missing in isoform 2.

VSP_007359

Natural variant

7

1

H → Q in a colorectal cancer sample; somatic mutation. Ref.22

VAR_036063

Natural variant

180

1

I → V High frequency in healthy individuals; found in a patient with sporadic pseudohypoaldosteronism type I; increases transcription transactivation at low aldosterone concentrations. dbSNP rs5522. Ref.2 Ref.3 Ref.16 Ref.19

VAR_014623

Natural variant

241

1

A → V High frequency in healthy individuals; found in a patient with sporadic pseudohypoaldosteronism type I; reduces transcription transactivation upon aldosterone binding. Ref.2 Ref.3 Ref.19

VAR_015625

Natural variant

444

1

N → T: dbSNP rs5523. Ref.16

VAR_014624

Natural variant

537

1

R → Q: dbSNP rs5526. Ref.16

VAR_014625

Natural variant

554

1

N → S: dbSNP rs5527. Ref.16

VAR_014626

Natural variant

633

1

G → R in PHA1; reduces transcription transactivation upon aldosterone binding. Ref.20

VAR_031268

Natural variant

645

1

C → S in PHA1. Ref.23

VAR_031269

Natural variant

659

1

R → S in PHA1. Ref.23

VAR_031270

Natural variant

759

1

P → S in PHA1. Ref.23

VAR_031271

Natural variant

769

1

L → P in PHA1. Ref.23

VAR_031272

Natural variant

770

1

N → K in PHA1. Ref.23

VAR_031273

Natural variant

776

1

Q → R in PHA1; reduces aldosterone binding. Ref.20

VAR_031274

Natural variant

805

1

S → P in PHA1. Ref.23

VAR_031275

Natural variant

810

1

S → L in early onset hypertension; alters receptor specificity and leads to constitutive activation. dbSNP rs41511344. Ref.13 Ref.15 Ref.18

VAR_015626

Natural variant

815

1

S → R in PHA1. Ref.23

VAR_031276

Natural variant

818

1

S → L in PHA1; abolishes translocation to the nucleus and transcription transactivation upon aldosterone binding. Ref.21

VAR_031277

Natural variant

826

1

F → Y: dbSNP rs13306592.

VAR_029311

Natural variant

924

1

L → P in PHA1; abolishes transcription transactivation upon aldosterone binding. Ref.17 Ref.20

VAR_015627

Natural variant

972

1

E → G in PHA1; reduces affinity for aldosterone and transcription transactivation. Ref.21

VAR_031278

Natural variant

979

1

L → P in PHA1; loss of aldosterone binding and transcription transactivation. Ref.20

VAR_031279

Experimental info

Mutagenesis

767

1

S → N: Loss of transcription transactivation. Ref.13

Mutagenesis

767

1

S → Q: Strong decrease of transcription transactivation. Ref.13

Mutagenesis

770

1

N → A, D, H, Q, S or T: Abolishes aldosterone binding and transcription transactivation. Ref.13 Ref.10

Mutagenesis

776

1

Q → A: Reduces aldosterone binding and transcription transactivation. Ref.15 Ref.10

Mutagenesis

782

1

K → E: Decreased coactivator binding. Ref.14

Mutagenesis

785

1

K → E: Loss of coactivator binding. Ref.14

Mutagenesis

796

1

E → R: Decreased coactivator binding. Ref.14

Mutagenesis

808

1

C → S: Increases aldosterone-binding. Ref.9

Mutagenesis

810

1

S → M: Alters receptor specificity. Ref.18

Mutagenesis

817

1

R → A: Reduces aldosterone binding and transcription transactivation. Ref.15 Ref.10

Mutagenesis

849

1

C → S: Strongly decreases affinity for aldosterone and transcription transactivation. Ref.9

Mutagenesis

942

1

C → S: Abolishes steroid binding and transcription transactivation. Ref.9

Mutagenesis

945

1

T → A: Decreases aldosterone-binding and cortisol-binding. Ref.13 Ref.10

Mutagenesis

952

1

L → A: Reduces transcription transactivation. Ref.11

Mutagenesis

953

1

K → A: Slightly reduces aldosterone binding and abolishes transcription transactivation. Ref.11

Mutagenesis

954

1

V → A: Reduces aldosterone binding and abolishes transcription transactivation. Ref.11

Mutagenesis

956

1

F → A: Abolishes aldosterone binding and transcription transactivation. Ref.11

Mutagenesis

957

1

P → A: Slightly reduces aldosterone binding and transcription transactivation. Ref.11

Secondary structure

1

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984

Helix Strand Turn

Details...

Helix

738 – 745

8

Helix

762 – 784

23

Helix

790 – 792

3

Helix

795 – 822

28

Beta strand

825 – 830

6

Beta strand

833 – 835

3

Turn

837 – 840

4

Helix

841 – 843

3

Turn

846 – 848

3

Helix

849 – 862

14

Helix

866 – 877

12

Beta strand

879 – 882

4

Helix

889 – 907

19

Helix

918 – 947

30

Helix

949 – 952

4

Helix

961 – 971

11

Beta strand

976 – 978

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1988. Version 1. Checksum: 8300CD1A18C1858A	FASTA	984	107,067
	10 20 30 40 50 60 METKGYHSLP EGLDMERRWG QVSQAVERSS LGPTERTDEN NYMEIVNVSC VSGAIPNNST 70 80 90 100 110 120 QGSSKEKQEL LPCLQQDNNR PGILTSDIKT ELESKELSAT VAESMGLYMD SVRDADYSYE 130 140 150 160 170 180 QQNQQGSMSP AKIYQNVEQL VKFYKGNGHR PSTLSCVNTP LRSFMSDSGS SVNGGVMRAI 190 200 210 220 230 240 VKSPIMCHEK SPSVCSPLNM TSSVCSPAGI NSVSSTTASF GSFPVHSPIT QGTPLTCSPN 250 260 270 280 290 300 AENRGSRSHS PAHASNVGSP LSSPLSSMKS SISSPPSHCS VKSPVSSPNN VTLRSSVSSP 310 320 330 340 350 360 ANINNSRCSV SSPSNTNNRS TLSSPAASTV GSICSPVNNA FSYTASGTSA GSSTLRDVVP 370 380 390 400 410 420 SPDTQEKGAQ EVPFPKTEEV ESAISNGVTG QLNIVQYIKP EPDGAFSSSC LGGNSKINSD 430 440 450 460 470 480 SSFSVPIKQE STKHSCSGTS FKGNPTVNPF PFMDGSYFSF MDDKDYYSLS GILGPPVPGF 490 500 510 520 530 540 DGNCEGSGFP VGIKQEPDDG SYYPEASIPS SAIVGVNSGG QSFHYRIGAQ GTISLSRSAR 550 560 570 580 590 600 DQSFQHLSSF PPVNTLVESW KSHGDLSSRR SDGYPVLEYI PENVSSSTLR SVSTGSSRPS 610 620 630 640 650 660 KICLVCGDEA SGCHYGVVTC GSCKVFFKRA VEGQHNYLCA GRNDCIIDKI RRKNCPACRL 670 680 690 700 710 720 QKCLQAGMNL GARKSKKLGK LKGIHEEQPQ QQQPPPPPPP PQSPEEGTTY IAPAKEPSVN 730 740 750 760 770 780 TALVPQLSTI SRALTPSPVM VLENIEPEIV YAGYDSSKPD TAENLLSTLN RLAGKQMIQV 790 800 810 820 830 840 VKWAKVLPGF KNLPLEDQIT LIQYSWMCLS SFALSWRSYK HTNSQFLYFA PDLVFNEEKM 850 860 870 880 890 900 HQSAMYELCQ GMHQISLQFV RLQLTFEEYT IMKVLLLLST IPKDGLKSQA AFEEMRTNYI 910 920 930 940 950 960 KELRKMVTKC PNNSGQSWQR FYQLTKLLDS MHDLVSDLLE FCFYTFRESH ALKVEFPAML 970 980 VEIISDQLPK VESGNAKPLY FHRK
	Isoform 2. Checksum: EEFC58BB02FA0812	FASTA	706	75,052
	10 20 30 40 50 60 METKGYHSLP EGLDMERRWG QVSQAVERSS LGPTERTDEN NYMEIVNVSC VSGAIPNNST 70 80 90 100 110 120 QGSSKEKQEL LPCLQQDNNR PGILTSDIKT ELESKELSAT VAESMGLYMD SVRDADYSYE 130 140 150 160 170 180 QQNQQGSMSP AKIYQNVEQL VKFYKGNGHR PSTLSCVNTP LRSFMSDSGS SVNGGVMRAI 190 200 210 220 230 240 VKSPIMCHEK SPSVCSPLNM TSSVCSPAGI NSVSSTTASF GSFPVHSPIT QGTPLTCSPN 250 260 270 280 290 300 AENRGSRSHS PAHASNVGSP LSSPLSSMKS SISSPPSHCS VKSPVSSPNN VTLRSSVSSP 310 320 330 340 350 360 ANINNSRCSV SSPSNTNNRS TLSSPAASTV GSICSPVNNA FSYTASGTSA GSSTLRDVVP 370 380 390 400 410 420 SPDTQEKGAQ EVPFPKTEEV ESAISNGVTG QLNIVQYIKP EPDGAFSSSC LGGNSKINSD 430 440 450 460 470 480 SSFSVPIKQE STKHSCSGTS FKGNPTVNPF PFMDGSYFSF MDDKDYYSLS GILGPPVPGF 490 500 510 520 530 540 DGNCEGSGFP VGIKQEPDDG SYYPEASIPS SAIVGVNSGG QSFHYRIGAQ GTISLSRSAR 550 560 570 580 590 600 DQSFQHLSSF PPVNTLVESW KSHGDLSSRR SDGYPVLEYI PENVSSSTLR SVSTGSSRPS 610 620 630 640 650 660 KICLVCGDEA SGCHYGVVTC GSCKVFFKRA VEGQHNYLCA GRNDCIIDKI RRKNCPACRL 670 680 690 700 QKCLQAGMNL GERRCISLPC MNYARGCTKS AFSSFDCSSP LKNTPS
	Isoform 3. Checksum: D6257319E5482C86	FASTA	988	107,572
	10 20 30 40 50 60 METKGYHSLP EGLDMERRWG QVSQAVERSS LGPTERTDEN NYMEIVNVSC VSGAIPNNST 70 80 90 100 110 120 QGSSKEKQEL LPCLQQDNNR PGILTSDIKT ELESKELSAT VAESMGLYMD SVRDADYSYE 130 140 150 160 170 180 QQNQQGSMSP AKIYQNVEQL VKFYKGNGHR PSTLSCVNTP LRSFMSDSGS SVNGGVMRAI 190 200 210 220 230 240 VKSPIMCHEK SPSVCSPLNM TSSVCSPAGI NSVSSTTASF GSFPVHSPIT QGTPLTCSPN 250 260 270 280 290 300 AENRGSRSHS PAHASNVGSP LSSPLSSMKS SISSPPSHCS VKSPVSSPNN VTLRSSVSSP 310 320 330 340 350 360 ANINNSRCSV SSPSNTNNRS TLSSPAASTV GSICSPVNNA FSYTASGTSA GSSTLRDVVP 370 380 390 400 410 420 SPDTQEKGAQ EVPFPKTEEV ESAISNGVTG QLNIVQYIKP EPDGAFSSSC LGGNSKINSD 430 440 450 460 470 480 SSFSVPIKQE STKHSCSGTS FKGNPTVNPF PFMDGSYFSF MDDKDYYSLS GILGPPVPGF 490 500 510 520 530 540 DGNCEGSGFP VGIKQEPDDG SYYPEASIPS SAIVGVNSGG QSFHYRIGAQ GTISLSRSAR 550 560 570 580 590 600 DQSFQHLSSF PPVNTLVESW KSHGDLSSRR SDGYPVLEYI PENVSSSTLR SVSTGSSRPS 610 620 630 640 650 660 KICLVCGDEA SGCHYGVVTC GSCKVFFKRA VEGKCSWQHN YLCAGRNDCI IDKIRRKNCP 670 680 690 700 710 720 ACRLQKCLQA GMNLGARKSK KLGKLKGIHE EQPQQQQPPP PPPPPQSPEE GTTYIAPAKE 730 740 750 760 770 780 PSVNTALVPQ LSTISRALTP SPVMVLENIE PEIVYAGYDS SKPDTAENLL STLNRLAGKQ 790 800 810 820 830 840 MIQVVKWAKV LPGFKNLPLE DQITLIQYSW MCLSSFALSW RSYKHTNSQF LYFAPDLVFN 850 860 870 880 890 900 EEKMHQSAMY ELCQGMHQIS LQFVRLQLTF EEYTIMKVLL LLSTIPKDGL KSQAAFEEMR 910 920 930 940 950 960 TNYIKELRKM VTKCPNNSGQ SWQRFYQLTK LLDSMHDLVS DLLEFCFYTF RESHALKVEF 970 980 PAMLVEIISD QLPKVESGNA KPLYFHRK
	Isoform 4 (Delta). Checksum: BEC8DD3A6A855903	FASTA	867	94,359
	10 20 30 40 50 60 METKGYHSLP EGLDMERRWG QVSQAVERSS LGPTERTDEN NYMEIVNVSC VSGAIPNNST 70 80 90 100 110 120 QGSSKEKQEL LPCLQQDNNR PGILTSDIKT ELESKELSAT VAESMGLYMD SVRDADYSYE 130 140 150 160 170 180 QQNQQGSMSP AKIYQNVEQL VKFYKGNGHR PSTLSCVNTP LRSFMSDSGS SVNGGVMRAI 190 200 210 220 230 240 VKSPIMCHEK SPSVCSPLNM TSSVCSPAGI NSVSSTTASF GSFPVHSPIT QGTPLTCSPN 250 260 270 280 290 300 AENRGSRSHS PAHASNVGSP LSSPLSSMKS SISSPPSHCS VKSPVSSPNN VTLRSSVSSP 310 320 330 340 350 360 ANINNSRCSV SSPSNTNNRS TLSSPAASTV GSICSPVNNA FSYTASGTSA GSSTLRDVVP 370 380 390 400 410 420 SPDTQEKGAQ EVPFPKTEEV ESAISNGVTG QLNIVQYIKP EPDGAFSSSC LGGNSKINSD 430 440 450 460 470 480 SSFSVPIKQE STKHSCSGTS FKGNPTVNPF PFMDGSYFSF MDDKDYYSLS GILGPPVPGF 490 500 510 520 530 540 DGNCEGSGFP VGIKQEPDDG SYYPEASIPS SAIVGVNSGG QSFHYRIGAQ GTISLSRSAR 550 560 570 580 590 600 DQSFQHLSSF PPVNTLVESW KSHGDLSSRR SDGYPVLEYI PENVSSSTLR SVSTGSSRPS 610 620 630 640 650 660 KICLVCGDEA SGCHYGVVTC GSCKVFFKRA VEGQHNYLCA GRNDCIIDKI RRKNCPACRL 670 680 690 700 710 720 QKCLQAGMNL GGFKNLPLED QITLIQYSWM CLSSFALSWR SYKHTNSQFL YFAPDLVFNE 730 740 750 760 770 780 EKMHQSAMYE LCQGMHQISL QFVRLQLTFE EYTIMKVLLL LSTIPKDGLK SQAAFEEMRT 790 800 810 820 830 840 NYIKELRKMV TKCPNNSGQS WQRFYQLTKL LDSMHDLVSD LLEFCFYTFR ESHALKVEFP 850 860 AMLVEIISDQ LPKVESGNAK PLYFHRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor." Arriza J.L., Weinberger C., Cerelli G., Glaser T.M., Handelin B.L., Housman D.E., Evans R.M. Science 237:268-275(1987) [PubMed: 3037703] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION. Tissue: Kidney.
[2]	"A new human MR splice variant is a ligand-independent transactivator modulating corticosteroid action." Zennaro M.-C., Souque A., Viengchareun S., Poisson E., Lombes M. Mol. Endocrinol. 15:1586-1598(2001) [PubMed: 11518808] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4), TISSUE SPECIFICITY, INTERACTION WITH NCOA1; TIF1 AND NRIP1, VARIANTS VAL-180 AND VAL-241. Tissue: Heart.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS VAL-180 AND VAL-241.
[4]	"Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I." Geller D.S., Rodriguez-Soriano J., Vallo Boado A., Schifter S., Bayer M., Chang S.S., Lifton R.P. Nat. Genet. 19:279-281(1998) [PubMed: 9662404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 545-984, DISEASE.
[5]	"Overexpression and characterization of the human mineralocorticoid receptor." Alnemri E.S., Maksymowych A.B., Robertson N.M., Litwack G. J. Biol. Chem. 266:18072-18081(1991) [PubMed: 1655735] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION.
[6]	"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: 7495694] [Abstract] Cited for: IDENTIFICATION (ISOFORM 3). Tissue: Leukocyte.
[7]	"Tissue-specific expression of alpha and beta messenger ribonucleic acid isoforms of the human mineralocorticoid receptor in normal and pathological states." Zennaro M.-C., Farman N., Bonvalet J.-P., Lombes M. J. Clin. Endocrinol. Metab. 82:1345-1352(1997) [PubMed: 9141514] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"The unliganded mineralocorticoid receptor is associated with heat shock proteins 70 and 90 and the immunophilin FKBP-52." Bruner K.L., Derfoul A., Robertson N.M., Guerriero G., Fernandes-Alnemri T., Alnemri E.S., Litwack G. Recept. Signal Transduct. 7:85-98(1997) [PubMed: 9392437] [Abstract] Cited for: TERNARY COMPLEX WITH HSP90; HSP70 AND FKBP4, DISSOCIATION UPON ALDOSTERONE BINDING.
[9]	"Cysteines 849 and 942 of human mineralocorticoid receptor are crucial for steroid binding." Lupo B., Mesnier D., Auzou G. Biochemistry 37:12153-12159(1998) [PubMed: 9724527] [Abstract] Cited for: MUTAGENESIS OF CYS-808; CYS-849 AND CYS-942.
[10]	"Mechanistic aspects of mineralocorticoid receptor activation." Hellal-Levy C., Fagart J., Souque A., Rafestin-Oblin M.-E. Kidney Int. 57:1250-1255(2000) [PubMed: 10760050] [Abstract] Cited for: MUTAGENESIS OF ASN-770; GLN-776; ARG-817 AND THR-945.
[11]	"Crucial role of the H11-H12 loop in stabilizing the active conformation of the human mineralocorticoid receptor." Hellal-Levy C., Fagart J., Souque A., Wurtz J.-M., Moras D., Rafestin-Oblin M.-E. Mol. Endocrinol. 14:1210-1221(2000) [PubMed: 10935545] [Abstract] Cited for: INTERACTION WITH NCOA1; TIF1 AND NRIP1, MUTAGENESIS OF LEU-952; LYS-953; VAL-954; PHE-956 AND PRO-957.
[12]	"The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2." Odermatt A., Arnold P., Frey F.J. J. Biol. Chem. 276:28484-28492(2001) [PubMed: 11350956] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH HSD11B2.
[13]	"A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor." Bledsoe R.K., Madauss K.P., Holt J.A., Apolito C.J., Lambert M.H., Pearce K.H., Stanley T.B., Stewart E.L., Trump R.P., Willson T.M., Williams S.P. J. Biol. Chem. 280:31283-31293(2005) [PubMed: 15967794] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 712-984 OF MUTANT SER-808 IN COMPLEXES WITH AGONIST AND ANTAGONISTS, CHARACTERIZATION OF VARIANT EARLY ONSET HYPERTENSION LEU-810, MUTAGENESIS OF SER-767; ASN-770 AND THR-945.
[14]	"Structural and biochemical mechanisms for the specificity of hormone binding and coactivator assembly by mineralocorticoid receptor." Li Y., Suino K., Daugherty J., Xu H.E. Mol. Cell 19:367-380(2005) [PubMed: 16061183] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 732-984 OF MUTANT SER-808 IN COMPLEX WITH STEROID LIGAND AND NCOA2, SUBUNIT, MUTAGENESIS OF LYS-782; LYS-785 AND GLU-796.
[15]	"Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension." Fagart J., Huyet J., Pinon G.M., Rochel M., Mayer C., Rafestin-Oblin M.-E. Nat. Struct. Mol. Biol. 12:554-555(2005) [PubMed: 15908963] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 731-984 OF MUTANT LEU-810 IN COMPLEXES WITH STEROID AGONISTS, CHARACTERIZATION OF VARIANT EARLY ONSET HYPERTENSION LEU-810, MUTAGENESIS OF GLN-776 AND ARG-817.
[16]	"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis." Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A. Nat. Genet. 22:239-247(1999) [PubMed: 10391210] [Abstract] Cited for: VARIANTS VAL-180; THR-444; GLN-537 AND SER-554.
[17]	"A novel missense mutation of mineralocorticoid receptor gene in one Japanese family with a renal form of pseudohypoaldosteronism type 1." Tajima T., Kitagawa H., Yokoya S., Tachibana K., Adachi M., Nakae J., Suwa S., Katoh S., Fujieda K. J. Clin. Endocrinol. Metab. 85:4690-4694(2000) [PubMed: 11134129] [Abstract] Cited for: CHARACTERIZATION OF VARIANT PHA1 PRO-924.
[18]	"Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy." Geller D.S., Farhi A., Pinkerton N., Fradley M., Moritz M., Spitzer A., Meinke G., Tsai F.T.F., Sigler P.B., Lifton R.P. Science 289:119-123(2000) [PubMed: 10884226] [Abstract] Cited for: VARIANT EARLY ONSET HYPERTENSION LEU-810, MUTAGENESIS OF SER-810.
[19]	"Functional polymorphisms in the mineralocorticoid receptor and amirolide-sensitive sodium channel genes in a patient with sporadic pseudohypoaldosteronism." Arai K., Nakagomi Y., Iketani M., Shimura Y., Amemiya S., Ohyama K., Shibasaki T. Hum. Genet. 112:91-97(2003) [PubMed: 12483305] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS VAL-180 AND VAL-241.
[20]	"Different inactivating mutations of the mineralocorticoid receptor in fourteen families affected by type I pseudohypoaldosteronism." Sartorato P., Lapeyraque A.-L., Armanini D., Kuhnle U., Khaldi Y., Salomon R., Abadie V., Di Battista E., Naselli A., Racine A., Bosio M., Caprio M., Poulet-Young V., Chabrolle J.-P., Niaudet P., De Gennes C., Lecornec M.-H., Poisson E. , Fusco A.M., Loli P., Lombes M., Zennaro M.-C. J. Clin. Endocrinol. Metab. 88:2508-2517(2003) [PubMed: 12788847] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS PHA1 ARG-633; ARG-776; PRO-924 AND PRO-979.
[21]	"Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1." Riepe F.G., Finkeldei J., de Sanctis L., Einaudi S., Testa A., Karges B., Peter M., Viemann M., Groetzinger J., Sippell W.G., Fejes-Toth G., Krone N. J. Clin. Endocrinol. Metab. 91:4552-4561(2006) [PubMed: 16954160] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS PHA1 LEU-818 AND GLY-972.
[22]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-7.
[23]	"Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism." Pujo L., Fagart J., Gary F., Papadimitriou D.T., Claes A., Jeunemaitre X., Zennaro M.-C. Hum. Mutat. 28:33-40(2007) [PubMed: 16972228] [Abstract] Cited for: VARIANTS PHA1 SER-645; SER-659; SER-759; PRO-769; LYS-770; PRO-805 AND ARG-815.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Wikipedia

Mineralocorticoid receptor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M16801 mRNA. Translation: AAA59571.1.
AJ315514 mRNA. Translation: CAC67405.1.
AJ315515 mRNA. Translation: CAC67406.1.
AC069272 Genomic DNA. No translation available.
AC093678 Genomic DNA. No translation available.
AC093881 Genomic DNA. No translation available.
AC104691 Genomic DNA. No translation available.
AC106899 Genomic DNA. No translation available.
AF068623 , AF068616, AF068617, AF068618, AF068619, AF068620, AF068621, AF068622 Genomic DNA. Translation: AAC63513.1.

IPI

IPI00027744.
IPI00248972.
IPI00248973.
IPI00248974.

PIR

A29513.

RefSeq

NP_000892.2.

UniGene

Hs.163924

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Y9R	X-ray	1.96	A/B	731-984	[»]
1YA3	X-ray	2.34	A/B/C	731-984	[»]
2A3I	X-ray	1.95	A	732-984	[»]
2AA2	X-ray	1.95	A	712-984	[»]
2AA5	X-ray	2.20	A/B	712-984	[»]
2AA6	X-ray	1.95	A/B	712-984	[»]
2AA7	X-ray	2.20	A	712-984	[»]
2AAX	X-ray	1.75	A/B	712-984	[»]
2AB2	X-ray	1.85	A/B	712-984	[»]
2ABI	X-ray	2.33	A/B/C	731-984	[»]
2OAX	X-ray	2.29	A/B/C/D/E/F	731-984	[»]

SMR

P08235. Positions 599-676.

ModBase

Search...

Protein-protein interaction databases

STRING

P08235.

PTM databases

PhosphoSite

P08235.

Proteomic databases

PRIDE

P08235.

Genome annotation databases

Ensembl

ENST00000358102; ENSP00000350815; ENSG00000151623; Homo sapiens. [Genome view]

GeneID

4306.

Organism-specific databases

GeneCards

GC04M149219.

H-InvDB

HIX0024570.

HGNC

HGNC:7979. NR3C2.

HPA

CAB009155.

MIM

177735. phenotype.
600983. gene.
605115. phenotype.

Orphanet

88660. Hypertension due to gain-of-function mutations in the mineralocorticoid receptor.
756. Pseudohypoaldosteronism, type 1.
171871. Renal pseudohypoaldosteronism type 1.

PharmGKB

PA242.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09421.

HOVERGEN

P08235.

Enzyme and pathway databases

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P08235.

Bgee

P08235.

CleanEx

HS_NR3C2.

Genevestigator

P08235.

GermOnline

ENSG00000151623. Homo sapiens.

Family and domain databases

InterPro

IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]

Gene3D

G3DSA:3.30.50.10. Znf_NHR/GATA. 1 hit.

Pfam

PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PRINTS

PR00047. STROIDFINGER.

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

P08235.

DrugBank

DB01134. Desoxycorticosterone Pivalate.
DB00700. Eplerenone.
DB00687. Fludrocortisone.
DB00421. Spironolactone.

NextBio

16949.

SOURCE

Search...

Entry information

Entry name

MCR_HUMAN

Accession

Primary (citable) accession number: P08235
Secondary accession number(s): Q96KQ8, Q96KQ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	August 1, 1988
Last modified:	February 9, 2010
This is version 124 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.