bioax途径由Reactome数据库中“NR1D1 (REV-ERBA)结合血红素、PPARGC1A基因并招募辅抑制子”转化而来。 NR1D1 (REV-ERBA)结合血红素，PPARGC1A基因，并招募辅抑制子 NR1D1 (REV-ERBA)结合血红素，PPARGC1A基因，并招募辅抑制子 NR1D1 (REV-ERBA)结合血红素和PGC-1alpha基因启动子(PPARGC1A)。REV-ERBA:血红素复合物招募辅抑制子NCoR和HDAC3并抑制转录。 作者:May, Bruce, 2015-01-15 评论:Delaunay, F, 2012-01-28 评论:Somers, Julia, 2021年01月23日 编辑本文:May, Bruce, 2015-01-15 Reactome DB_ID: 4686147 1 核浆 去 0005654 运用:ENSG00000109189 PPARGC1A USP46 PPARGC1A Reactome //www.joaskin.com 智人 NCBI分类法 9606 运用 ENSG00000109189 Reactome DB_ID: 442464 1 UniProt: O15379 HDAC3 HDAC3 HDAC3 主要负责核心组蛋白(H2A, H2B, H3, H4) n端赖氨酸残基的去乙酰化，以及其他一些非组蛋白底物。组蛋白去乙酰化为表观遗传抑制提供了一个标签，并在转录调控、细胞周期进展和发育事件中发挥重要作用。组蛋白去乙酰化酶通过形成大的多蛋白复合物起作用。通过去乙酰化增强子元件上的H3 'Lys-27' (H3K27)，拮抗EP300乙酰转移酶活性，抑制近端基因表达，参与BCL6转录抑制因子活性。可能通过与锌指转录因子YY1结合参与转录调控;增加YY1抑制活动。需要抑制POU1F1转录因子的转录。作为分子伴侣，将磷酸化的NR2C1转移到PML体进行sumo化(PubMed:21444723, PubMed:23911289)。与XBP1亚型1一起，在PI(3)K/mTORC2/ akt依赖的信号通路中激活nfe2l2介导的HMOX1转录因子基因表达，从而导致内皮细胞(EC)在干扰流/氧化应激下存活(PubMed:25190803)。以脱乙酰酶活性独立的方式(通过相似性)调节生物钟的转录激活和抑制阶段。 During the activation phase, promotes the accumulation of ubiquitinated ARNTL/BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and ARNTL/BMAL1 (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). Serves as a corepressor of RARA, causing its deacetylation and inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). Interacts with SETD5 (By similarity).SUBUNIT Interacts with HDAC7 and HDAC9. Forms a heterologous complex at least with YY1. Interacts with DAXX, HDAC10 and DACH1. Found in a complex with NCOR1 and NCOR2. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2. Interacts with BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY. Interacts with BTBD14B. Interacts with GLIS2. Interacts (via the DNA-binding domain) with NR2C1; the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation. Component of the Notch corepressor complex. Interacts with CBFA2T3 and NKAP. Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Interacts with and deacetylates MAPK14. Interacts with ZMYND15. Interacts with SMRT/NCOR2 and BCL6 on DNA enhancer elements. Interacts with INSM1 (PubMed:10655483, PubMed:10669754, PubMed:10860984, PubMed:10898795, PubMed:11006275, PubMed:11466315, PubMed:11533236, PubMed:11861901, PubMed:14525983, PubMed:14633989, PubMed:15297880, PubMed:15927959, PubMed:16569215, PubMed:18417529, PubMed:19409814, PubMed:23911289). Interacts with XBP1 isoform 1; the interaction occurs in endothelial cell (EC) under disturbed flow (PubMed:25190803). Interacts (via C-terminus) with CCAR2 (via N-terminus). Interacts with and deacetylates MEF2D. Interacts with BEND3. Interacts with NKAPL (By similarity). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts weakly with CRY1; this interaction is enhanced in the presence of FBXL3 (By similarity). Interacts with FBXL3 and ARNTL/BMAL1 (By similarity). Interacts with NCOR1 (By similarity). Interacts with RARA (PubMed:28167758).TISSUE SPECIFICITY Widely expressed.INDUCTION Up-regulated by disturbed flow in umbilical vein endothelial cells in vitro (PubMed:25190803).PTM Sumoylated in vitro.SIMILARITY Belongs to the histone deacetylase family. HD type 1 subfamily. UniProt O15379 链坐标 1 平等的 428 平等的 Reactome DB_ID: 1368125 1 ferriheme b (ChEBI: 36144) ferriheme b ChEBI 36144 Reactome DB_ID: 442501 1 UniProt: O75376 NCOR1 NCOR1 NCOR1 KIAA1047 功能通过核受体介导转录抑制(PubMed:20812024)。促进组蛋白去乙酰化和抑制染色质结构形成的复合物的一部分，这可能会阻碍基础转录因子的进入。参与BCL6产生的转录抑制因子活性。被ZBTB7A招募到靶基因上的雄激素应答元件/ARE，负调控雄激素受体信号转导和雄激素诱导的细胞增殖(PubMed:20812024)。介导了nr1d1依赖的抑制和TSHB表达的昼夜调控(通过相似性)。NCOR1-HDAC3复合物调节核心时钟基因ARTNL/BMAL1和肝脏脂质代谢相关基因的昼夜表达(相似)。亚单位形成一个大的共抑制复合物，包含SIN3A/B和组蛋白去乙酰化酶HDAC1和HDAC2。在没有配体的情况下，该复合物与甲状腺受体(TR)和视黄酸受体(RAR)结合。与RARA直接交互;RARA三甲基化促进了相互作用。N-Cor抑制复合物的成分，至少由CBFA2T3, HEXIM1, NCOR1, NCOR2, HDAC3, TBL1X, TBL1XR1, CORO2A和GPS2组成。 Interacts with ZBTB33; the interaction serves to recruit the N-CoR complex to promoter regions containing methylated CpG dinucleotides. Interacts with TRIM28 and KDM3A. Interacts (via the RD1 domain) with BAZ1A (via its N-terminal); the interaction corepresses a number of NCOR1-regulated genes. Interacts with BCL6, C1D, DACH1, HEXIM1, HDAC7, RORA, RORC, SAP30, SIAH2, SIN3A and SIN3B. May interact with DEAF1. Interacts with RXRA. Interacts with SETD5 (By similarity). Interacts with VDR (PubMed:28698609). Interacts with ZBTB7A (PubMed:20812024). Interacts with AR (PubMed:20812024). Interacts with HDAC3 (By similarity).DOMAIN The N-terminal region contains three independent domains that are capable of mediating transcriptional repression (RD1, RD2 and RD3).DOMAIN The C-terminal region contains two separate nuclear receptor-interacting domains (ID1 and ID2), each of which contains a conserved sequence referred to as the CORNR box. This motif is necessary and sufficient for binding to unligated nuclear hormone receptors, while sequences flanking the CORNR box determine the precise nuclear hormone receptor specificity (By similarity).PTM Ubiquitinated; mediated by SIAH2 and leading to its subsequent proteasomal degradation.SIMILARITY Belongs to the N-CoR nuclear receptor corepressors family. UniProt O75376 1 平等的 2440 平等的 Reactome DB_ID: 375499 1 UniProt: P20393 NR1D1 NR1D1 THRAL HREV NR1D1 原发性高血压 FUNCTION转录抑制，其协调昼夜节律和代谢途径中血红素依赖性。复杂的转录机制的积分分量管辖昼夜节律性和形式通过直接抑制核心时钟分量ARTNL / BMAL1，CLOCK和CRY1表达的昼夜节律钟的临界负肢体。还调节参与代谢功能，包括脂质和胆汁酸代谢，脂肪生成，糖异生和巨噬细胞的炎症反应的基因。充当用于血红素受体刺激其与NCOR1 / HDAC3辅阻遏物复杂的相互作用，增强转录抑制。识别两类DNA反应元件的其靶基因的启动子内，并且可以与DNA结合作为单体或同型二聚体，这取决于反应元件的性质。结合作为单体的共有半位点基序组成的反应元件5 ' - [A / G] GGTCA-3' 由A / T-丰富的5' 序列（RevRE），或作为同二聚体之前到直接重复由两个核苷酸（RevDR-2）间隔开的核心基序的。作为RORα（RORA）函数的有效竞争性阻遏物和通过抑制PPARGC1A，血红素合成的有效诱导的表达调节其配体血红素的水平。调节通过抑制APOC3的表达和通过影响固醇响应元件结合蛋白（SREBPs）的活性脂质代谢;阻遏INSIG2与SREBPs这反过来支配酶的节律表达与甾醇键的功能和脂肪酸合成的蛋白水解激活干涉。 Regulates gluconeogenesis via repression of G6PC1 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).SUBUNIT Binds DNA as a monomer or a homodimer (PubMed:9660968). Interacts with C1D, NR2E3 and SP1 (By similarity). Interacts with OPHN1 (via C-terminus) (PubMed:21874017). Interacts with ZNHIT1 (PubMed:17892483). Interacts with PER2; the interaction associates PER2 to ARNTL promoter region (PubMed:22170608). Interacts with CRY1 (PubMed:22170608). Interacts with CCAR2 (PubMed:23398316). Interacts with SIAH2 (PubMed:26392558). Interacts with CDK1 (By similarity). Interacts with FBXW7 (PubMed:27238018). Interacts with HUWE1 (PubMed:20534529). Interacts with NR0B2 (By similarity). Interacts with NFIL3 (By similarity). Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (By similarity).TISSUE SPECIFICITY Widely expressed. Expressed at high levels in the liver, adipose tissue, skeletal muscle and brain. Also expressed in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and macrophages. Expression oscillates diurnally in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as in peripheral tissues. Expression increases during the differentiation of pre-adipocytes into mature adipocytes. Expressed at high levels in some squamous carcinoma cell lines.DOMAIN Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.PTM Ubiquitinated, leading to its proteasomal degradation (PubMed:16484495, PubMed:23398316, PubMed:20534529). Ubiquitinated by SIAH2; leading to its proteasomal degradation (PubMed:26392558). Ubiquitinated by the SCF(FBXW7) complex when phosphorylated by CDK1 leading to its proteasomal degradation (By similarity). Rapidly ubiquitinated in response to inflammatory triggers and sumoylation is a prerequisite to its ubiquitination (By similarity).PTM Sumoylated by UBE2I, desumoylated by SENP1, and sumoylation is a prerequisite to its ubiquitination.PTM Phosphorylated by CSNK1E; phosphorylation enhances its cytoplasmic localization.PTM Undergoes lysosome-mediated degradation in a time-dependent manner in the liver.SIMILARITY Belongs to the nuclear hormone receptor family. NR1 subfamily. UniProt P20393 1 平等的 614 平等的 Reactome DB_ID: 5663272 1 NR1D1:血红素辅阻遏物:PPARGC1A基因(核浆) NR1D1:血红素辅阻遏物:PPARGC1A基因 Reactome DB_ID: 4686147 1 Reactome DB_ID: 1368079 1 NR1D1 (REV-ERBA):血红素辅阻遏物(核浆) NR1D1 (REV-ERBA):血红素:辅阻遏物 Reactome DB_ID: 442464 1 1 平等的 428 平等的 Reactome DB_ID: 442501 1 1 平等的 2440 平等的 Reactome DB_ID: 1368127 1 NR1D1 (REV-ERBA):血红素(核浆) NR1D1 (REV-ERBA):血红素 Reactome DB_ID: 1368125 1 Reactome DB_ID: 375499 1 1 平等的 614 平等的 Reactome数据库ID Release 77 1368127 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1368127 Reactome r - hsa - 1368127 1 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1368127.1 Reactome数据库ID Release 77 1368079 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1368079 Reactome r - hsa - 1368079 1 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1368079.1 Reactome数据库ID Release 77 5663272 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=5663272 Reactome r - hsa - 5663272 1 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5663272.1 Reactome数据库ID Release 77 5663258 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=5663258 Reactome r - hsa - 5663258 2 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5663258.2 19710360 Pubmed 2009 血红素受体的负反馈维持稳态 吴,N 阴,我 Hanniman, EA 乔希,年代 Lazar,马 基因Dev 23:2201-9