Gene/Proteome Database (LMPD)

LMPD ID
LMP012982
Gene ID
252917
Species
Rattus norvegicus (Rat)
Gene Name
nuclear receptor subfamily 1, group D, member 1
Gene Symbol
Nr1d1
Synonyms
REV-ERBAALPHA;
Alternate Names
nuclear receptor subfamily 1 group D member 1; EAR-1; rev-erb alpha; rev-erbA-alpha; V-erbA-related protein 1; V-erbA-related protein EAR-1;
Chromosome
10
Map Location
10q31
Summary
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, Feb 2014]
Orthologs
View orthologs and multiple alignments for Nr1d1

Proteins

nuclear receptor subfamily 1 group D member 1 isoform 1
Refseq ID NP_001106893
Protein GI 164663889
UniProt ID Q63503
mRNA ID NM_001113422
Length 615
MTTLDSNNNTGGVITYIGSSGSSPSRTSPESLYSDSSNGSFQSLTQGCPTYFPPSPTGSLTQDPARSFGTVPPSLSDDSSPSSASSSSSSSSSSFYNGSPPGSLQVAMEDSSRVSPSKGTSNITKLNGMVLLCKVCGDVASGFHYGVHACEGCKGFFRRSIQQNIQYKRCLKNENCSIVRINRNRCQQCRFKKCLSVGMSRDAVRFGRIPKREKQRMLAEMQNAMNLANNQLSSLCPLETSPAPHPTSGSVGPSPPPAPAPTPLVGFSQFPQQLTPPRSPSPEPTVEDVISQVARAHREIFTYAHDKLGTSPGNFNANHASGSPPATTPQCWESQGCPSTPNDNNLLAAQRHNEALNGLRQGPSSYPPTWPSGPAHHSCHQPNSNGHRLCPTHVYSAPEGKAPANGLRQGNTKNVLLACPMNMYPHGRSGRTVQEIWEDFSMSFTPAVREVVEFAKHIPGFRDLSQHDQVTLLKAGTFEVLMVRFASLFNVKDQTVMFLSRTTYSLQELGAMGMGDLLNAMFDFSEKLNSLALTEEELGLFTAVVLVSADRSGMENSASVEQLQETLLRALRALVLKNRPSETSRFTKLLLKLPDLRTLNNMHSEKLLSFRVDAQ
nuclear receptor subfamily 1 group D member 1 isoform 2
Refseq ID NP_665718
Protein GI 164663891
UniProt ID Q63503
mRNA ID NM_145775
Length 508
MEDSSRVSPSKGTSNITKLNGMVLLCKVCGDVASGFHYGVHACEGCKGFFRRSIQQNIQYKRCLKNENCSIVRINRNRCQQCRFKKCLSVGMSRDAVRFGRIPKREKQRMLAEMQNAMNLANNQLSSLCPLETSPAPHPTSGSVGPSPPPAPAPTPLVGFSQFPQQLTPPRSPSPEPTVEDVISQVARAHREIFTYAHDKLGTSPGNFNANHASGSPPATTPQCWESQGCPSTPNDNNLLAAQRHNEALNGLRQGPSSYPPTWPSGPAHHSCHQPNSNGHRLCPTHVYSAPEGKAPANGLRQGNTKNVLLACPMNMYPHGRSGRTVQEIWEDFSMSFTPAVREVVEFAKHIPGFRDLSQHDQVTLLKAGTFEVLMVRFASLFNVKDQTVMFLSRTTYSLQELGAMGMGDLLNAMFDFSEKLNSLALTEEELGLFTAVVLVSADRSGMENSASVEQLQETLLRALRALVLKNRPSETSRFTKLLLKLPDLRTLNNMHSEKLLSFRVDAQ

Gene Information

Entrez Gene ID
252917
Gene Name
nuclear receptor subfamily 1, group D, member 1
Gene Symbol
Nr1d1
Species
Rattus norvegicus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005737 ISS:UniProtKB C cytoplasm
GO:0030425 ISS:UniProtKB C dendrite
GO:0043197 ISS:UniProtKB C dendritic spine
GO:0005634 ISS:UniProtKB C nucleus
GO:0001046 ISS:UniProtKB F core promoter sequence-specific DNA binding
GO:0003700 IEA:InterPro F sequence-specific DNA binding transcription factor activity
GO:0003707 IEA:InterPro F steroid hormone receptor activity
GO:0001222 ISS:UniProtKB F transcription corepressor binding
GO:0008270 IEA:InterPro F zinc ion binding
GO:0030154 IEA:UniProtKB-KW P cell differentiation
GO:0032922 ISS:UniProtKB P circadian regulation of gene expression
GO:0060086 ISS:UniProtKB P circadian temperature homeostasis
GO:0005978 ISS:UniProtKB P glycogen biosynthetic process
GO:0045892 ISS:UniProtKB P negative regulation of transcription, DNA-templated
GO:0070859 ISS:UniProtKB P positive regulation of bile acid biosynthetic process
GO:0045893 IDA:UniProtKB P positive regulation of transcription, DNA-templated
GO:0010498 ISS:UniProtKB P proteasomal protein catabolic process
GO:2000188 ISS:UniProtKB P regulation of cholesterol homeostasis
GO:0042752 IDA:UniProtKB P regulation of circadian rhythm
GO:0045598 ISS:UniProtKB P regulation of fat cell differentiation
GO:0035947 ISS:UniProtKB P regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter
GO:0061178 ISS:UniProtKB P regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0019216 ISS:UniProtKB P regulation of lipid metabolic process
GO:0061469 ISS:UniProtKB P regulation of type B pancreatic cell proliferation
GO:0044321 ISS:UniProtKB P response to leptin
GO:0006351 IEA:UniProtKB-KW P transcription, DNA-templated

KEGG Pathway Links

KEGG Pathway ID Description
ko04710 Circadian rhythm
rno04710 Circadian rhythm

REACTOME Pathway Links

REACTOME Pathway ID Description
5954332 BMAL1:CLOCK,NPAS2 activates circadian gene expression
5954223 Circadian Clock
5953288 Fatty acid, triacylglycerol, and ketone body metabolism
5953330 Gene Expression
5953833 Generic Transcription Pathway
5953250 Metabolism
5953289 Metabolism of lipids and lipoproteins
5954147 Nuclear Receptor transcription pathway
5954333 PPARA activates gene expression
5954224 REV-ERBA represses gene expression
5954225 RORA activates circadian gene expression
5954222 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)

Domain Information

InterPro Annotations

Accession Description
IPR008946 Nuclear hormone receptor, ligand-binding
IPR000536 Nuclear hormone receptor, ligand-binding, core
IPR001723 Steroid hormone receptor
IPR013088 Zinc finger, NHR/GATA-type
IPR001628 Zinc finger, nuclear hormone receptor-type

UniProt Annotations

Entry Information

Gene Name
nuclear receptor subfamily 1, group D, member 1
Protein Entry
NR1D1_RAT
UniProt ID
Q63503
Species
Rat

Comments

Comment Type Description
Domain Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Function 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
Induction In bladder smooth muscle cells, exhibits night/day variations with a peak time at circadian time (CT) 4-12 and a trough at CT16-24
Ptm Ubiquitinated, leading to its proteasomal degradation
Sequence Caution Sequence=AAA74939.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ;
Similarity Belongs to the nuclear hormone receptor family. NR1 subfamily
Similarity Contains 1 nuclear receptor DNA-binding domain
Subcellular Location Nucleus {ECO:0000255|PROSITE- ProRule:PRU00407}. Cytoplasm . Cell projection, dendrite . Cell projection, dendritic spine . Note=Localizes to the cytoplasm, dendrites and dendritic spine in the presence of OPHN1
Subunit Binds DNA as a monomer or a homodimer. Interacts with C1D, NR2E3, SP1 and ZNHIT1. Interacts with OPHN1 (via C-terminus). Interacts with PER2; the interaction associates PER2 to ARNTL promoter region. Interacts with CRY1. Interacts with CCAR2 (By similarity). {ECO:0000250|UniProtKB:P20393, ECO:0000269|PubMed:21874017}.

Identical and Related Proteins

Unique RefSeq proteins for LMP012982 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
164663889 RefSeq NP_001106893 615 nuclear receptor subfamily 1 group D member 1 isoform 1
164663891 RefSeq NP_665718 508 nuclear receptor subfamily 1 group D member 1 isoform 2

Identical Sequences to LMP012982 proteins

Reference Database Accession Length Protein Name
GI:164663891 GenBank EDM05953.1 508 nuclear receptor subfamily 1, group D, member 1, isoform CRA_a [Rattus norvegicus]

Related Sequences to LMP012982 proteins

Reference Database Accession Length Protein Name
GI:164663889 GenBank AAH62047.1 615 Nr1d1 protein [Rattus norvegicus]
GI:164663889 GenBank EDL16166.1 615 nuclear receptor subfamily 1, group D, member 1 [Mus musculus]
GI:164663891 GenBank EDM05953.1 508 nuclear receptor subfamily 1, group D, member 1, isoform CRA_a [Rattus norvegicus]
GI:164663891 GenBank EDM05954.1 614 nuclear receptor subfamily 1, group D, member 1, isoform CRA_b [Rattus norvegicus]
GI:164663889 GenBank EDM05954.1 614 nuclear receptor subfamily 1, group D, member 1, isoform CRA_b [Rattus norvegicus]
GI:164663891 RefSeq NP_001106893.1 615 nuclear receptor subfamily 1 group D member 1 isoform 1 [Rattus norvegicus]
GI:164663889 SwissProt Q63503.2 615 RecName: Full=Nuclear receptor subfamily 1 group D member 1; AltName: Full=Rev-erbA-alpha; AltName: Full=V-erbA-related protein 1; Short=EAR-1 [Rattus norvegicus]
GI:164663891 SwissProt Q63503.2 615 RecName: Full=Nuclear receptor subfamily 1 group D member 1; AltName: Full=Rev-erbA-alpha; AltName: Full=V-erbA-related protein 1; Short=EAR-1 [Rattus norvegicus]