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Overview

Uniprot IDQ14995
Protein NameNuclear receptor subfamily 1 group D member 2
Gene NameNR1D2
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
138 IQQNIQYKKCLKNEN
80 DCSMKTSKSSAPGMT

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 BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the 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 nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and also negatively regulates the expression of NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle via repression of genes involved in lipid metabolism and myogenesis including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic lipid metabolism via the repression of APOC3. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). In addition to its activity as a repressor, can also act as a transcriptional activator. Acts as a transcriptional activator of the sterol regulatory element-binding protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in the skeletal muscle (By similarity). Plays a role in the regulation of circadian sleep/wake cycle; essential for maintaining wakefulness during the dark phase or active period (By similarity). Key regulator of skeletal muscle mitochondrial function; negatively regulates the skeletal muscle expression of core clock genes and genes involved in mitochondrial biogenesis, fatty acid beta-oxidation and lipid metabolism (By similarity). May play a role in the circadian control of neutrophilic inflammation in the lung (By similarity)

Protein Sequence

10 MEVNAGGVIA 20 YISSSSSASS 30 PASCHSEGSE 40 NSFQSSSSSV 50 PSSPNSSNSD 60 TNGNPKNGDL 70 ANIEGILKND 80 RIDCSMKTSK 90 SSAPGMTKSH 100 SGVTKFSGMV 110 LLCKVCGDVA 120 SGFHYGVHAC 130 EGCKGFFRRS 140 IQQNIQYKKC 150 LKNENCSIMR 160 MNRNRCQQCR 170 FKKCLSVGMS 180 RDAVRFGRIP 190 KREKQRMLIE 200 MQSAMKTMMN 210 SQFSGHLQND 220 TLVEHHEQTA 230 LPAQEQLRPK 240 PQLEQENIKS 250 SSPPSSDFAK 260 EEVIGMVTRA 270 HKDTFMYNQE 280 QQENSAESMQ 290 PQRGERIPKN 300 MEQYNLNHDH 310 CGNGLSSHFP 320 CSESQQHLNG 330 QFKGRNIMHY 340 PNGHAICIAN 350 GHCMNFSNAY 360 TQRVCDRVPI 370 DGFSQNENKN 380 SYLCNTGGRM 390 HLVCPMSKSP 400 YVDPHKSGHE 410 IWEEFSMSFT 420 PAVKEVVEFA 430 KRIPGFRDLS 440 QHDQVNLLKA 450 GTFEVLMVRF 460 ASLFDAKERT 470 VTFLSGKKYS 480 VDDLHSMGAG 490 DLLNSMFEFS 500 EKLNALQLSD 510 EEMSLFTAVV 520 LVSADRSGIE 530 NVNSVEALQE 540 TLIRALRTLI 550 MKNHPNEASI 560 FTKLLLKLPD 570 LRSLNNMHSE ELLAFKVHP

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
Molecular Function GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific
Molecular Function GO:0004879 nuclear receptor activity
Molecular Function GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular Function GO:1990837 sequence-specific double-stranded DNA binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0030154 cell differentiation
Biological Process GO:0048512 circadian behavior
Biological Process GO:0006351 DNA-templated transcription
Biological Process GO:0097009 energy homeostasis
Biological Process GO:0009755 hormone-mediated signaling pathway
Biological Process GO:0030522 intracellular receptor signaling pathway
Biological Process GO:0055088 lipid homeostasis
Biological Process GO:0045892 negative regulation of DNA-templated transcription
Biological Process GO:0050728 negative regulation of inflammatory response
Biological Process GO:0000122 negative regulation of transcription by RNA polymerase II
Biological Process GO:0045893 positive regulation of DNA-templated transcription
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0042752 regulation of circadian rhythm
Biological Process GO:0006355 regulation of DNA-templated transcription
Biological Process GO:0050727 regulation of inflammatory response
Biological Process GO:0019216 regulation of lipid metabolic process
Biological Process GO:2001014 regulation of skeletal muscle cell differentiation

Reference

PMID: N/A