ASpdb: an integrative knowledgebase of human protein isoforms from experimental and AI-predicted structures

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	Protein Summary
	AS Summary
	Protein Functional Features
	Gene Isoform Structures and Expression Levels
	Protein Structures
	pLDDT Score Distribution
	Ramachandran Plot of Protein Structures
	Potential Active Site Information
	Protein Structure and Feature Comparision
	Protein-Protein Interaction
	Related Drugs
	Related Diseases
	Clinically Important Variants

Protein:NR3C2

Protein Summary

Gene summary

Gene name: NR3C2
ASpdb.0 ID: 4306
	Gene
Gene symbol	NR3C2
Gene ID	4306
Gene name	nuclear receptor subfamily 3 group C member 2
Synonyms	MCR\|MLR\|MR\|NR3C2VIT
Cytomap	4q31.23
Type of gene	protein-coding
Description	mineralocorticoid receptoraldosterone receptormineralocorticoid receptor 1mineralocorticoid receptor 2mineralocorticoid receptor delta
Modification date	20240411
UniProtAcc	P08235

Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Gene	NR3C2	GO:0005654	nucleoplasm	-
Gene	NR3C2	GO:0043235	receptor complex	23382219
Gene	NR3C2	GO:1990837	sequence-specific double-stranded DNA binding	28473536

AS Summary

Information of the canonical protein with experimentally identified structure from PDB (2023).

UniProt Acc	File name	PDB ID	Method	Resolution	Chain	Start	End
P08235-1	P08235-1_2aax_A.pdb	2AAX	X-ray	1.75	A	722	983

ASpdb's canonical and alternatively spliced isoform information.

accession_id

gene_name

canonical_id

alternative_id

canonical_length

alternative_length

canonical_start

canonical_end

type

originalSEQ

variationSEQ

alternative_start

alternative_end

P08235

NR3C2

P08235-1

P08235-2

984

706

672

706

Substitution

ARKSKKLGKLKGIHEEQPQQQQPPPPPPPPQSPEE

ERRCISLPCMNYARGCTKSAFSSFDCSSPLKNTPS

672

706

P08235

NR3C2

P08235-1

P08235-2

984

706

707

984

Deletion

none

706

P08235

NR3C2

P08235-1

P08235-3

984

988

633

Substitution

GKCSW

633

637

P08235

NR3C2

P08235-1

P08235-4

984

867

672

788

Deletion

none

671

Multiple sequence alignment of our canonical and alternatively spliced NR3C2

Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of NR3C2

UniProt-id	ENSG	ENST	ENSP
P08235-1	ENSG00000151623.15	ENST00000344721.8	ENSP00000341390.4
P08235-1	ENSG00000151623.15	ENST00000358102.8	ENSP00000350815.3
P08235-2	ENSG00000151623.15	ENST00000342437.8	ENSP00000343907.4
P08235-3	ENSG00000151623.15	ENST00000511528.1	ENSP00000421481.1
P08235-3	ENSG00000151623.15	ENST00000625323.2	ENSP00000486719.1
P08235-4	ENSG00000151623.15	ENST00000512865.5	ENSP00000423510.1

UniProt-id	NM ID	NP ID
P08235-1	NM_000901.4	NP_000892.2
P08235-3	XM_011531975.1	XP_011530277.1
P08235-4	NM_001166104.1	NP_001159576.1

Amino acid sequences of our canonical and alternatively spliced NR3C2

accession_id	Protein sequence
P08235-1	METKGYHSLPEGLDMERRWGQVSQAVERSSLGPTERTDENNYMEIVNVSCVSGAIPNNSTQGSSKEKQELLPCLQQDNNRPGILTSDIKT ELESKELSATVAESMGLYMDSVRDADYSYEQQNQQGSMSPAKIYQNVEQLVKFYKGNGHRPSTLSCVNTPLRSFMSDSGSSVNGGVMRAV VKSPIMCHEKSPSVCSPLNMTSSVCSPAGINSVSSTTASFGSFPVHSPITQGTPLTCSPNVENRGSRSHSPAHASNVGSPLSSPLSSMKS SISSPPSHCSVKSPVSSPNNVTLRSSVSSPANINNSRCSVSSPSNTNNRSTLSSPAASTVGSICSPVNNAFSYTASGTSAGSSTLRDVVP SPDTQEKGAQEVPFPKTEEVESAISNGVTGQLNIVQYIKPEPDGAFSSSCLGGNSKINSDSSFSVPIKQESTKHSCSGTSFKGNPTVNPF PFMDGSYFSFMDDKDYYSLSGILGPPVPGFDGNCEGSGFPVGIKQEPDDGSYYPEASIPSSAIVGVNSGGQSFHYRIGAQGTISLSRSAR DQSFQHLSSFPPVNTLVESWKSHGDLSSRRSDGYPVLEYIPENVSSSTLRSVSTGSSRPSKICLVCGDEASGCHYGVVTCGSCKVFFKRA VEGQHNYLCAGRNDCIIDKIRRKNCPACRLQKCLQAGMNLGARKSKKLGKLKGIHEEQPQQQQPPPPPPPPQSPEEGTTYIAPAKEPSVN TALVPQLSTISRALTPSPVMVLENIEPEIVYAGYDSSKPDTAENLLSTLNRLAGKQMIQVVKWAKVLPGFKNLPLEDQITLIQYSWMCLS SFALSWRSYKHTNSQFLYFAPDLVFNEEKMHQSAMYELCQGMHQISLQFVRLQLTFEEYTIMKVLLLLSTIPKDGLKSQAAFEEMRTNYI
P08235-2	METKGYHSLPEGLDMERRWGQVSQAVERSSLGPTERTDENNYMEIVNVSCVSGAIPNNSTQGSSKEKQELLPCLQQDNNRPGILTSDIKT ELESKELSATVAESMGLYMDSVRDADYSYEQQNQQGSMSPAKIYQNVEQLVKFYKGNGHRPSTLSCVNTPLRSFMSDSGSSVNGGVMRAV VKSPIMCHEKSPSVCSPLNMTSSVCSPAGINSVSSTTASFGSFPVHSPITQGTPLTCSPNVENRGSRSHSPAHASNVGSPLSSPLSSMKS SISSPPSHCSVKSPVSSPNNVTLRSSVSSPANINNSRCSVSSPSNTNNRSTLSSPAASTVGSICSPVNNAFSYTASGTSAGSSTLRDVVP SPDTQEKGAQEVPFPKTEEVESAISNGVTGQLNIVQYIKPEPDGAFSSSCLGGNSKINSDSSFSVPIKQESTKHSCSGTSFKGNPTVNPF PFMDGSYFSFMDDKDYYSLSGILGPPVPGFDGNCEGSGFPVGIKQEPDDGSYYPEASIPSSAIVGVNSGGQSFHYRIGAQGTISLSRSAR DQSFQHLSSFPPVNTLVESWKSHGDLSSRRSDGYPVLEYIPENVSSSTLRSVSTGSSRPSKICLVCGDEASGCHYGVVTCGSCKVFFKRA
P08235-3	METKGYHSLPEGLDMERRWGQVSQAVERSSLGPTERTDENNYMEIVNVSCVSGAIPNNSTQGSSKEKQELLPCLQQDNNRPGILTSDIKT ELESKELSATVAESMGLYMDSVRDADYSYEQQNQQGSMSPAKIYQNVEQLVKFYKGNGHRPSTLSCVNTPLRSFMSDSGSSVNGGVMRAV VKSPIMCHEKSPSVCSPLNMTSSVCSPAGINSVSSTTASFGSFPVHSPITQGTPLTCSPNVENRGSRSHSPAHASNVGSPLSSPLSSMKS SISSPPSHCSVKSPVSSPNNVTLRSSVSSPANINNSRCSVSSPSNTNNRSTLSSPAASTVGSICSPVNNAFSYTASGTSAGSSTLRDVVP SPDTQEKGAQEVPFPKTEEVESAISNGVTGQLNIVQYIKPEPDGAFSSSCLGGNSKINSDSSFSVPIKQESTKHSCSGTSFKGNPTVNPF PFMDGSYFSFMDDKDYYSLSGILGPPVPGFDGNCEGSGFPVGIKQEPDDGSYYPEASIPSSAIVGVNSGGQSFHYRIGAQGTISLSRSAR DQSFQHLSSFPPVNTLVESWKSHGDLSSRRSDGYPVLEYIPENVSSSTLRSVSTGSSRPSKICLVCGDEASGCHYGVVTCGSCKVFFKRA VEGKCSWQHNYLCAGRNDCIIDKIRRKNCPACRLQKCLQAGMNLGARKSKKLGKLKGIHEEQPQQQQPPPPPPPPQSPEEGTTYIAPAKE PSVNTALVPQLSTISRALTPSPVMVLENIEPEIVYAGYDSSKPDTAENLLSTLNRLAGKQMIQVVKWAKVLPGFKNLPLEDQITLIQYSW MCLSSFALSWRSYKHTNSQFLYFAPDLVFNEEKMHQSAMYELCQGMHQISLQFVRLQLTFEEYTIMKVLLLLSTIPKDGLKSQAAFEEMR
P08235-4	METKGYHSLPEGLDMERRWGQVSQAVERSSLGPTERTDENNYMEIVNVSCVSGAIPNNSTQGSSKEKQELLPCLQQDNNRPGILTSDIKT ELESKELSATVAESMGLYMDSVRDADYSYEQQNQQGSMSPAKIYQNVEQLVKFYKGNGHRPSTLSCVNTPLRSFMSDSGSSVNGGVMRAV VKSPIMCHEKSPSVCSPLNMTSSVCSPAGINSVSSTTASFGSFPVHSPITQGTPLTCSPNVENRGSRSHSPAHASNVGSPLSSPLSSMKS SISSPPSHCSVKSPVSSPNNVTLRSSVSSPANINNSRCSVSSPSNTNNRSTLSSPAASTVGSICSPVNNAFSYTASGTSAGSSTLRDVVP SPDTQEKGAQEVPFPKTEEVESAISNGVTGQLNIVQYIKPEPDGAFSSSCLGGNSKINSDSSFSVPIKQESTKHSCSGTSFKGNPTVNPF PFMDGSYFSFMDDKDYYSLSGILGPPVPGFDGNCEGSGFPVGIKQEPDDGSYYPEASIPSSAIVGVNSGGQSFHYRIGAQGTISLSRSAR DQSFQHLSSFPPVNTLVESWKSHGDLSSRRSDGYPVLEYIPENVSSSTLRSVSTGSSRPSKICLVCGDEASGCHYGVVTCGSCKVFFKRA VEGQHNYLCAGRNDCIIDKIRRKNCPACRLQKCLQAGMNLGGFKNLPLEDQITLIQYSWMCLSSFALSWRSYKHTNSQFLYFAPDLVFNE EKMHQSAMYELCQGMHQISLQFVRLQLTFEEYTIMKVLLLLSTIPKDGLKSQAAFEEMRTNYIKELRKMVTKCPNNSGQSWQRFYQLTKL

Protein Functional Features

Main function of this protein. (from UniProt)

NR3C2 (go to UniProt):P08235

Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at
download page
* Minus value of BPloci means that the break pointn is located before the CDS.

- Retained protein feature among the 13 regional features.

Accession_id	Subsection	Start	End	Funcitonal feature	Splicing information
P08235	Domain	726	964	Note=NR LBD;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU01189	Type=Deletion;Start=707;End=984
P08235	Domain	726	964	Note=NR LBD;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU01189	Type=Deletion;Start=672;End=788
P08235	DNA binding	603	668	Note=Nuclear receptor;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00407	Type=Substitution;Start=633;End=633
P08235	Region	669	725	Note=Hinge	Type=Substitution;Start=672;End=706
P08235	Region	669	725	Note=Hinge	Type=Deletion;Start=707;End=984
P08235	Region	669	725	Note=Hinge	Type=Deletion;Start=672;End=788
P08235	Region	684	710	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=672;End=706
P08235	Region	684	710	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=707;End=984
P08235	Region	684	710	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=672;End=788
P08235	Region	782	785	Note=Important for coactivator binding	Type=Deletion;Start=707;End=984
P08235	Region	782	785	Note=Important for coactivator binding	Type=Deletion;Start=672;End=788
P08235	Compositional bias	690	706	Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=672;End=706
P08235	Compositional bias	690	706	Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Deletion;Start=672;End=788

Gene Isoform Structures and Expression Levels for NR3C2

Gene structures of our canonical and alternative spliced genes of NR3C2
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Expression levels of gene isoforms across GTEx.

Expression levels of gene isoforms across TCGA.

Protein Structures

PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.

3D view using mol* of P08235-1

3D view using mol* of P08235-2

3D view using mol* of P08235-3

3D view using mol* of P08235-4

pLDDT Score Distribution

pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

pLDDT distribution across the protein length of P08235-1

pLDDT distribution across the protein length of P08235-2

pLDDT distribution across the protein length of P08235-3

pLDDT distribution across the protein length of P08235-4

Ramachandran Plot of Protein Structures

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.

Ramachandran plot of P08235-1

Ramachandran plot of P08235-2

Potential Active Site Information

The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.

UniProt-id	Site score	Size	D score	Volume	Exposure	Enclosure	Contact	Phobic	Philic	Balance	Don/Acc	Residues
P08235-1	1.284	110	1.35	149.891	0.209	0.982	1.22	3.142	0.551	5.702	2.508	766,769,770,772,773,776,806,807,810,811,814,817,82 9,845,852,938,941,942,945,956,960
P08235-2	1.011	88	1.078	380.044	0.687	0.66	0.81	0.991	0.615	1.613	0.651	599,601,602,604,612,613,615,616,617,618,667,669,67 2,674,675,676,678,679,680,681,683,684
P08235-3	1.289	109	1.357	150.577	0.216	0.981	1.25	3.864	0.525	7.36	3.313	770,773,774,776,777,780,810,811,814,815,818,821,83 3,849,852,856,942,945,946,949,960
P08235-4	1.132	92	1.233	321.734	0.598	0.74	0.84	2.329	0.345	6.754	4.373	109,112,113,116,469,470,472,473,673,678,681,682,68 5,686,689,692,756,757,760,842,845,846

Protein Structure and Feature Comparision

Protein Structure Comparision Using Template Modeling Scores (TM-score).

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)

3D view using mol* of P08235-1_P08235-1_2aax_A.pdb

Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P08235-1_2aax_A_P08235-2.pdb

3D view using mol* of P08235-1_2aax_A_P08235-3.pdb

3D view using mol* of P08235-1_2aax_A_P08235-4.pdb

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P08235-1_P08235-2.pdb

3D view using mol* of P08235-1_P08235-3.pdb

3D view using mol* of P08235-1_P08235-4.pdb

Protein Feature Comparison of the protein sequendary structures among the protiens.

./stats/secondary_structure/figure/P08235-1_vs_P08235-2.png

./stats/secondary_structure/figure/P08235-1_vs_P08235-3.png

./stats/secondary_structure/figure/P08235-1_vs_P08235-4.png

Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.

./stats/relative_asa/P08235-1_vs_P08235-2.png

./stats/relative_asa/P08235-1_vs_P08235-3.png

./stats/relative_asa/P08235-1_vs_P08235-4.png

Protein-Protein Interaction

Interactors from UniProt.

Accession_id

Subsection

Start

End

Funcitonal feature

Splicing information

Interactors from STRING.

Gene name

Interactors

Related Drugs to NR3C2

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession	Gene name	DrugBank ID	Drug name	Drug group	Actions
P08235	NR3C2	DB13943	Testosterone cypionate	approved
P08235	NR3C2	DB02901	Stanolone	illicit, investigational
P08235	NR3C2	DB04630	Aldosterone	experimental, investigational	agonist
P08235	NR3C2	DB02998	Metribolone	experimental
P08235	NR3C2	DB00393	Nimodipine	approved, investigational	antagonist
P08235	NR3C2	DB00700	Eplerenone	approved	antagonist
P08235	NR3C2	DB08906	Fluticasone furoate	approved	antagonist
P08235	NR3C2	DB01395	Drospirenone	approved	antagonist
P08235	NR3C2	DB01023	Felodipine	approved, investigational	antagonist
P08235	NR3C2	DB06780	Desoxycorticosterone acetate	approved	agonist
P08235	NR3C2	DB00687	Fludrocortisone	approved, investigational	agonist
P08235	NR3C2	DB01013	Clobetasol propionate	approved	agonist
P08235	NR3C2	DB13944	Testosterone enanthate	approved
P08235	NR3C2	DB13951	Stanolone acetate	experimental
P08235	NR3C2	DB00421	Spironolactone	approved	antagonist
P08235	NR3C2	DB04652	Corticosterone	experimental
P08235	NR3C2	DB13867	Fluticasone	approved, experimental	antagonist
P08235	NR3C2	DB16165	Finerenone	approved, investigational	antagonist
P08235	NR3C2	DB00396	Progesterone	approved, vet_approved	antagonist, agonist
P08235	NR3C2	DB00624	Testosterone	approved, investigational	ligand
P08235	NR3C2	DB00588	Fluticasone propionate	approved	antagonist
P08235	NR3C2	DB15114	Vamorolone	approved, investigational	antagonist
P08235	NR3C2	DB01134	Desoxycorticosterone pivalate	experimental, vet_approved	agonist

Related Diseases to NR3C2

Previous studies relating to the alternative splicing of NR3C2 and disease information from the MeSH term (PubMed)

Gene	PMID	Title	Abstract	MeSH ID	MeSH term
NR3C2	9141514	Tissue-specific expression of alpha and beta messenger ribonucleic acid isoforms of the human mineralocorticoid receptor in normal and pathological states.	Expression of the mineralocorticoid receptor (MR) is restricted to some sodium-transporting epithelia and a few nonepithelial target tissues. Determination of the genomic structure of the human MR (hMR) revealed two different untranslated exons (1alpha and 1beta), which splice alternatively into the common exon 2, giving rise to two hMR mRNA isoforms (hMR alpha and hMR beta). We have investigated expression of hMR transcripts in renal, cardiac, skin, and colonic tissue samples by in situ hybridization with exon 1alpha and 1beta specific riboprobes, using an exon 2 probe as internal control. Specific signals for either exon 1alpha- and 1beta-containing mRNAs were detected in typically hMR-expressing cells in all tissues analyzed. hMR alpha and hMR beta were present in distal tubules of the kidney, in cardiomyocytes, in enterocytes of the colonic mucosa, and in keratinocytes and sweat glands. Interestingly, although both isoforms appear to be expressed at approximately the same level, the relative abundance of each message compared with that of exon 2-containing mRNA strikingly differs among aldosterone target tissues, suggesting the possibility of other tissue-specific transcripts originating from alternative splicing. Finally, functional hypermineralocorticism was associated with reduced expression of hMR beta in sweat glands of two patients affected by Conn's and Liddle's syndrome, whereas normal levels of hMR isoforms were found in one case of pseudohypoaldosteronism. Altogether, our results indicate a differential, tissue-specific expression of hMR mRNA isoforms, hMR beta being down-regulated in situations of positive sodium balance, independently of aldosterone levels.	D011546	Pseudohypoaldosteronism

Clinically important variants in NR3C2

(ClinVar, 04/20/2024)

accession_id

uniprot_id

gene_name

Type

Variant

Clinical_significance