- EMDB-17542: Negative stain map of UBR5 (dimer) in complex with RARA/RXRA -
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基本情報
登録情報
データベース: EMDB / ID: EMD-17542
タイトル
Negative stain map of UBR5 (dimer) in complex with RARA/RXRA
マップデータ
Half-map A.
試料
複合体: UBR5 in complex with RARA/RXRA
タンパク質・ペプチド: UBR5
タンパク質・ペプチド: RARA
タンパク質・ペプチド: RXRA
キーワード
E3 / ubiquitin ligase / HECT / LIGASE
機能・相同性
機能・相同性情報
Sertoli cell fate commitment / positive regulation of binding / trachea cartilage development / heterochromatin boundary formation / glandular epithelial cell development / ventricular cardiac muscle cell differentiation / chondroblast differentiation / embryonic camera-type eye development / protein kinase B binding / negative regulation of granulocyte differentiation ...Sertoli cell fate commitment / positive regulation of binding / trachea cartilage development / heterochromatin boundary formation / glandular epithelial cell development / ventricular cardiac muscle cell differentiation / chondroblast differentiation / embryonic camera-type eye development / protein kinase B binding / negative regulation of granulocyte differentiation / growth plate cartilage development / protein K29-linked ubiquitination / cytoplasm protein quality control by the ubiquitin-proteasome system / positive regulation of transporter activity / positive regulation of T-helper 2 cell differentiation / prostate gland development / retinoic acid-responsive element binding / nuclear protein quality control by the ubiquitin-proteasome system / NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose / negative regulation of cartilage development / NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake / NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis / regulation of hematopoietic progenitor cell differentiation / protein branched polyubiquitination / positive regulation of thyroid hormone receptor signaling pathway / positive regulation of interleukin-13 production / positive regulation of interleukin-5 production / NR1H2 & NR1H3 regulate gene expression linked to lipogenesis / Carnitine shuttle / retinoic acid binding / HECT-type E3 ubiquitin transferase / outflow tract septum morphogenesis / response to vitamin A / cytoplasm protein quality control / protein K11-linked ubiquitination / TGFBR3 expression / positive regulation of vitamin D receptor signaling pathway / nuclear vitamin D receptor binding / heterocyclic compound binding / limb development / apoptotic cell clearance / regulation of myelination / Signaling by Retinoic Acid / ureteric bud development / DNA binding domain binding / ubiquitin-ubiquitin ligase activity / DNA-binding transcription repressor activity / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / protein kinase A binding / LBD domain binding / DNA repair-dependent chromatin remodeling / positive regulation of interleukin-4 production / face development / alpha-actinin binding / germ cell development / negative regulation of type II interferon production / nuclear steroid receptor activity / Synthesis of bile acids and bile salts / negative regulation of tumor necrosis factor production / positive regulation of cholesterol efflux / cellular response to estrogen stimulus / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Endogenous sterols / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / positive regulation of bone mineralization / response to retinoic acid / protein K48-linked ubiquitination / progesterone receptor signaling pathway / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / retinoic acid receptor signaling pathway / Recycling of bile acids and salts / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / hormone-mediated signaling pathway / positive regulation of cell cycle / cellular response to retinoic acid / : / Regulation of lipid metabolism by PPARalpha / peroxisome proliferator activated receptor signaling pathway / response to cytokine / positive regulation of neuron differentiation / peptide binding / BMAL1:CLOCK,NPAS2 activates circadian expression / negative regulation of miRNA transcription / mRNA regulatory element binding translation repressor activity / female pregnancy / Activation of gene expression by SREBF (SREBP) / liver development / transcription coregulator binding / ubiquitin binding / hippocampus development / negative regulation of smoothened signaling pathway / neural tube closure / RNA polymerase II transcription regulatory region sequence-specific DNA binding / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / Heme signaling / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / transcription coactivator binding / Cytoprotection by HMOX1 類似検索 - 分子機能
E3 ubiquitin ligase EDD, ubiquitin-associated domain / : / E3 ubiquitin ligase EDD / : / : / Poly(A)-binding protein C-terminal (PABC) domain profile. / C-terminal domain of Poly(A)-binding protein. Present also in Drosophila hyperplastics discs protein. / Polyadenylate-binding protein/Hyperplastic disc protein / PABC (PABP) domain / MLLE domain ...E3 ubiquitin ligase EDD, ubiquitin-associated domain / : / E3 ubiquitin ligase EDD / : / : / Poly(A)-binding protein C-terminal (PABC) domain profile. / C-terminal domain of Poly(A)-binding protein. Present also in Drosophila hyperplastics discs protein. / Polyadenylate-binding protein/Hyperplastic disc protein / PABC (PABP) domain / MLLE domain / Zinc finger, UBR-type / Zinc finger UBR-type profile. / Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway / Retinoic acid receptor / Regulator of chromosome condensation 1/beta-lactamase-inhibitor protein II / Nuclear/hormone receptor activator site AF-1 / Nuclear/hormone receptor activator site AF-1 / Retinoid X receptor/HNF4 / : / HECT domain / HECT, E3 ligase catalytic domain / HECT-domain (ubiquitin-transferase) / HECT domain profile. / Domain Homologous to E6-AP Carboxyl Terminus with / Nuclear hormone receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type / Double treble clef zinc finger, C4 type / Nuclear hormone receptors DNA-binding domain profile. / c4 zinc finger in nuclear hormone receptors / Nuclear hormone receptor, ligand-binding domain / Nuclear hormone receptor-like domain superfamily / Ligand-binding domain of nuclear hormone receptor / Nuclear receptor (NR) ligand-binding (LBD) domain profile. / Ligand binding domain of hormone receptors / Zinc finger, NHR/GATA-type 類似検索 - ドメイン・相同性
ジャーナル: Mol Cell / 年: 2023 タイトル: UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability. 著者: Jonathan M Tsai / Jacob D Aguirre / Yen-Der Li / Jared Brown / Vivian Focht / Lukas Kater / Georg Kempf / Brittany Sandoval / Stefan Schmitt / Justine C Rutter / Pius Galli / Colby R Sandate ...著者: Jonathan M Tsai / Jacob D Aguirre / Yen-Der Li / Jared Brown / Vivian Focht / Lukas Kater / Georg Kempf / Brittany Sandoval / Stefan Schmitt / Justine C Rutter / Pius Galli / Colby R Sandate / Jevon A Cutler / Charles Zou / Katherine A Donovan / Ryan J Lumpkin / Simone Cavadini / Paul M C Park / Quinlan Sievers / Charlie Hatton / Elizabeth Ener / Brandon D Regalado / Micah T Sperling / Mikołaj Słabicki / Jeonghyeon Kim / Rebecca Zon / Zinan Zhang / Peter G Miller / Roger Belizaire / Adam S Sperling / Eric S Fischer / Rafael Irizarry / Scott A Armstrong / Nicolas H Thomä / Benjamin L Ebert / 要旨: Nuclear hormone receptors (NRs) are ligand-binding transcription factors that are widely targeted therapeutically. Agonist binding triggers NR activation and subsequent degradation by unknown ligand- ...Nuclear hormone receptors (NRs) are ligand-binding transcription factors that are widely targeted therapeutically. Agonist binding triggers NR activation and subsequent degradation by unknown ligand-dependent ubiquitin ligase machinery. NR degradation is critical for therapeutic efficacy in malignancies that are driven by retinoic acid and estrogen receptors. Here, we demonstrate the ubiquitin ligase UBR5 drives degradation of multiple agonist-bound NRs, including the retinoic acid receptor alpha (RARA), retinoid x receptor alpha (RXRA), glucocorticoid, estrogen, liver-X, progesterone, and vitamin D receptors. We present the high-resolution cryo-EMstructure of full-length human UBR5 and a negative stain model representing its interaction with RARA/RXRA. Agonist ligands induce sequential, mutually exclusive recruitment of nuclear coactivators (NCOAs) and UBR5 to chromatin to regulate transcriptional networks. Other pharmacological ligands such as selective estrogen receptor degraders (SERDs) degrade their receptors through differential recruitment of UBR5 or RNF111. We establish the UBR5 transcriptional regulatory hub as a common mediator and regulator of NR-induced transcription.