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General description of the gene and encoded protein(s) using information from HGNC and Ensembl, as well as predictions made as well as predictions made by the Human Protein Atlas project.
The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.
The main location is characterized by presence in all tested cell lines and/or increased intensity compared to other locations.
Additional locations are characterized by either a markedly lower staining intensity than the main location, or that it is only observed in a subset of the cell lines.
Nuclear bodies
Cancer prognostic summary
Prognostic marker in melanoma (favourable) and colorectal cancer (unfavourable)
Brain specificityi
The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.
The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.
All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.
Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.
Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).
The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.
Useful information about the protein provided by UniProt.
Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components ARTNL/BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha-cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent manner. Represses the transcription of CYP2B10, CYP4A10 and CYP4A14 (By similarity). Represses the transcription of CES2 (By similarity). Represses and regulates the circadian expression of TSHB in a NCOR1-dependent manner (By similarity). Negatively regulates the protein stability of NR3C1 and influences the time-dependent subcellular distribution of NR3C1, thereby affecting its transcriptional regulatory activity (By similarity). Plays a critical role in the circadian control of neutrophilic inflammation in the lung; under resting, non-stress conditions, acts as a rhythmic repressor to limit inflammatory activity whereas in the presence of inflammatory triggers undergoes ubiquitin-mediated degradation thereby relieving inhibition of the inflammatory response (By similarity). Plays a key role in the circadian regulation of microglial activation and neuroinflammation; suppresses microglial activation through the NF-kappaB pathway in the central nervous system (By similarity). Plays a role in the regulation of the diurnal rhythms of lipid and protein metabolism in the skeletal muscle via transcriptional repression of genes controlling lipid and amino acid metabolism in the muscle (By similarity)....show less
Molecular function (UniProt)i
Keywords assigned by UniProt to proteins due to their particular molecular function.
Activator, DNA-binding, Receptor, Repressor
Biological process (UniProt)i
Keywords assigned by UniProt to proteins because they are involved in a particular biological process.
Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.
Heme, Iron, Metal-binding, Zinc
Gene summary (Entrez)i
Useful information about the gene from Entrez
This gene encodes a transcription factor that is a member of the nuclear receptor subfamily 1. The encoded protein is a ligand-sensitive transcription factor that negatively regulates the expression of core clock proteins. In particular this protein represses the circadian clock transcription factor aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL). This protein may also be involved in regulating genes that function in metabolic, inflammatory and cardiovascular processes. [provided by RefSeq, Jan 2013]...show less
TISSUE ATLASi
The Tissue Atlas contains information regarding the expression profiles of human genes both on the mRNA and protein level. The protein expression data from 44 normal human tissue types is derived from antibody-based protein profiling using immunohistochemistry.
The RNA specificity category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.
The RNA distribution category is based on mRNA expression levels in the analyzed samples based on a combination of data from HPA, GTEX and FANTOM5. The categories include: detected in all, detected in many, detected in some, detected in single and not detected.
A summary of the overall protein expression pattern across the analyzed normal tissues. The summary is based on knowledge-based annotation.
"Estimation of protein expression could not be performed. View primary data." is shown for genes analyzed with a knowledge-based approach where available RNA-seq and gene/protein characterization data has been evaluated as not sufficient in combination with immunohistochemistry data to yield a reliable estimation of the protein expression profile.
The Brain Atlas explores the protein expression in the mammalian brain by visualization and integration of data from three mammalian species (human, pig and mouse). Transcriptomics data combined with affinity-based protein in situ localization down to single cell detail is here available in a brain-centric sub atlas of the Human Protein Atlas.
The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category.
The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category.
The regional specificity category is based on mRNA expression levels in the analyzed brain samples, grouped into 10 main brain regions and calculated for the three different species. The human brain expression profile is based on a combination of data from GTEX and FANTOM5. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category.
Summary of data presented in the Cell Atlas and a representative image of subcellular localization. The Cell Atlas provides RNA expression data derived from RNA sequencing of a large panel of cell lines and protein localization data derived from antibody-based profiling by immunofluorescence confocal microscopy, using a subset of cell lines selected based on RNA expression.
The main location is characterized by presence in all tested cell lines and/or increased intensity compared to other locations. It is highlighted in the illustration to the right. If available, links to overrepresentation analyses in Reactome, a free, open-source, curated and peer reviewed biological pathway database, are provided. An analysis is done for the corresponding gene set of the proteome localizing to the main and additional locations of the protein on this page, respectively.
Localized to the Nuclear bodies
Cell line specificityi
The cell lines in the Human Protein Atlas have been analyzed by RNA-seq to estimate the transcript abundance of each protein-coding gene. The RNA-seq data was then used to classify all genes according to their cell line-specific expression into one of six different categories, defined based on the total set of all NX values in all analyzed cell lines.
The Blood Atlas contains single cell type information on genome-wide RNA expression profiles of human protein-coding genes covering various B- and T-cells, monocytes, granulocytes and dendritic cells. In addition, an analysis of the human secretome is presented. including annotation of the genes predicted to be actively secreted to human blood. An analysis of the proteins detected in human blood is also presented.
The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.
The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.
Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.
No
PATHOLOGY ATLASi
Summary of data presented in the Pathology Atlas , including mRNA and protein expression data from 17 different forms of human cancer, as well as correlation analysis of mRNA expression and patient survival. To the far left, a representative image of protein expression, based on immunohistochemistry, is shown. Next to it, a representative image of a Kaplan-Meier plot, based on correlation analysis. Images are clickable and redirect to pages with more Pathology Atlas data.
Prognostic marker in melanoma (favourable) and colorectal cancer (unfavourable)
Cancer specificity (RNA)i
Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.
Distribution of RNA expression in 17 cancer types is categorized as either detected in single, detected in some, detected in many, detected in all, or not detected.
Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Gene name
NR1D1 (HGNC Symbol)
Synonyms
ear-1, hRev, Rev-ErbAalpha, THRA1, THRAL
Description
Nuclear receptor subfamily 1 group D member 1 (HGNC Symbol)
Chromosome
17
Cytoband
q21.1
Chromosome location (bp)
40092787 - 40100725
Number of transcriptsi
Number of protein-coding transcribed from this gene as defined by Ensembl.
The protein browser displays the antigen location on the target protein(s) and the features of the target protein. The tabs at the top of the protein view section can be used to switch between the different splice variants to which an antigen has been mapped.
At the top of the view, the position of the antigen (identified by the corresponding HPA identifier) is shown as a green bar. A yellow triangle on the bar indicates a <100% sequence identity to the protein target.
Below the antigens, the maximum percent sequence identity of the protein to all other proteins from other human genes is displayed, using a sliding window of 10 aa residues (HsID 10) or 50 aa residues (HsID 50). The region with the lowest possible identity is always selected for antigen design, with a maximum identity of 60% allowed for designing a single-target antigen (read more).
The curve in blue displays the predicted antigenicity i.e. the tendency for different regions of the protein to generate an immune response, with peak regions being predicted to be more antigenic.The curve shows average values based on a sliding window approach using an in-house propensity scale. (read more).
If a signal peptide is predicted by a majority of the signal peptide predictors SPOCTOPUS, SignalP 4.0, and Phobius (turquoise) and/or transmembrane regions (orange) are predicted by MDM, these are displayed.
Low complexity regions are shown in yellow and InterPro regions in green. Common (purple) and unique (grey) regions between different splice variants of the gene are also displayed (read more), and at the bottom of the protein view is the protein scale.
NR1D1-201
PROTEIN INFORMATIONi
The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.
The ENSP identifier links to the Ensembl website protein summary, while the ENST identifier links to the Ensembl website transcript summary for the selected splice variant. The data in the UniProt column can be expanded to show links to all matching UniProt identifiers for this protein.
The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.
The Gene Ontology terms assigned to this protein are listed if expanding the Gene ontology column. The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide (according to a majority of the signal peptide predictors SPOCTOPUS, SignalP 4.0, and Phobius) and the number of predicted transmembrane region(s) (according to MDM) are also reported.
P20393 [Direct mapping] Nuclear receptor subfamily 1 group D member 1 F1D8S3 [Target identity:100%; Query identity:100%] Nuclear receptor Rev-ErbA-alpha; Nuclear receptor subfamily 1, group D, member 1
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Nuclear receptors Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Transcription factors Zinc-coordinating DNA-binding domains Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Peptideatlas)
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GO:0000122 [negative regulation of transcription from RNA polymerase II promoter] GO:0000790 [nuclear chromatin] GO:0000977 [RNA polymerase II regulatory region sequence-specific DNA binding] GO:0000978 [RNA polymerase II proximal promoter sequence-specific DNA binding] GO:0000981 [RNA polymerase II transcription factor activity, sequence-specific DNA binding] GO:0001046 [core promoter sequence-specific DNA binding] GO:0001078 [transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding] GO:0001222 [transcription corepressor binding] GO:0003677 [DNA binding] GO:0003700 [DNA binding transcription factor activity] GO:0003707 [steroid hormone receptor activity] GO:0003714 [transcription corepressor activity] GO:0004879 [nuclear receptor activity] GO:0005515 [protein binding] GO:0005634 [nucleus] GO:0005654 [nucleoplasm] GO:0005737 [cytoplasm] GO:0005978 [glycogen biosynthetic process] GO:0006351 [transcription, DNA-templated] GO:0006355 [regulation of transcription, DNA-templated] GO:0006367 [transcription initiation from RNA polymerase II promoter] GO:0007623 [circadian rhythm] GO:0008270 [zinc ion binding] GO:0010498 [proteasomal protein catabolic process] GO:0010871 [negative regulation of receptor biosynthetic process] GO:0016604 [nuclear body] GO:0019216 [regulation of lipid metabolic process] GO:0020037 [heme binding] GO:0030154 [cell differentiation] GO:0030425 [dendrite] GO:0030522 [intracellular receptor signaling pathway] GO:0032922 [circadian regulation of gene expression] GO:0034144 [negative regulation of toll-like receptor 4 signaling pathway] GO:0035947 [regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter] GO:0042752 [regulation of circadian rhythm] GO:0042995 [cell projection] GO:0043197 [dendritic spine] GO:0043401 [steroid hormone mediated signaling pathway] GO:0043565 [sequence-specific DNA binding] GO:0044212 [transcription regulatory region DNA binding] GO:0044321 [response to leptin] GO:0045598 [regulation of fat cell differentiation] GO:0045892 [negative regulation of transcription, DNA-templated] GO:0045893 [positive regulation of transcription, DNA-templated] GO:0046872 [metal ion binding] GO:0048511 [rhythmic process] GO:0060086 [circadian temperature homeostasis] GO:0061178 [regulation of insulin secretion involved in cellular response to glucose stimulus] GO:0061469 [regulation of type B pancreatic cell proliferation] GO:0070859 [positive regulation of bile acid biosynthetic process] GO:0071222 [cellular response to lipopolysaccharide] GO:2000188 [regulation of cholesterol homeostasis]
The Human Protein Atlas project is funded
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