複合体: 60S ribosome bound by the UFM1 ribosome E3 ligase complex.
複合体: UFM1 ribosome E3 ligase complex
タンパク質・ペプチド: x 1種
RNA: x 3種
タンパク質・ペプチド: x 41種
リガンド: x 3種
キーワード
UFM1 / Ligase / Ribosome / Complex
機能・相同性
機能・相同性情報
UFM1 ligase activity / positive regulation of reticulophagy / UFM1 transferase activity / positive regulation of proteolysis involved in protein catabolic process / protein K69-linked ufmylation / protein ufmylation / negative regulation of IRE1-mediated unfolded protein response / regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of T cell mediated immune response to tumor cell / negative regulation of T cell activation ...UFM1 ligase activity / positive regulation of reticulophagy / UFM1 transferase activity / positive regulation of proteolysis involved in protein catabolic process / protein K69-linked ufmylation / protein ufmylation / negative regulation of IRE1-mediated unfolded protein response / regulation of proteasomal ubiquitin-dependent protein catabolic process / negative regulation of T cell mediated immune response to tumor cell / negative regulation of T cell activation / regulation of intracellular estrogen receptor signaling pathway / translation at presynapse / embryonic brain development / exit from mitosis / eukaryotic 80S initiation complex / negative regulation of protein neddylation / response to insecticide / optic nerve development / regulation of G1 to G0 transition / axial mesoderm development / negative regulation of formation of translation preinitiation complex / regulation of translation involved in cellular response to UV / ribosomal protein import into nucleus / protein-DNA complex disassembly / 90S preribosome assembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / retinal ganglion cell axon guidance / ribosome disassembly / 転移酵素; アシル基を移すもの; アミノアシル基を移すもの / regulation of canonical NF-kappaB signal transduction / GAIT complex / positive regulation of DNA damage response, signal transduction by p53 class mediator / TORC2 complex binding / alpha-beta T cell differentiation / reticulophagy / G1 to G0 transition / middle ear morphogenesis / response to L-glutamate / cytoplasmic side of rough endoplasmic reticulum membrane / negative regulation of NF-kappaB transcription factor activity / negative regulation of ubiquitin protein ligase activity / homeostatic process / macrophage chemotaxis / lung morphogenesis / positive regulation of natural killer cell proliferation / Protein hydroxylation / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / blastocyst development / cellular response to actinomycin D / Response of EIF2AK4 (GCN2) to amino acid deficiency / positive regulation of signal transduction by p53 class mediator / negative regulation of ubiquitin-dependent protein catabolic process / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / hematopoietic stem cell differentiation / protein localization to nucleus / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / protein targeting / protein-RNA complex assembly / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / maturation of LSU-rRNA / rough endoplasmic reticulum / translation regulator activity / Maturation of protein E / positive regulation of glial cell proliferation / Maturation of protein E / ER Quality Control Compartment (ERQC) / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / negative regulation of protein ubiquitination / positive regulation of autophagy / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / cytosolic ribosome / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Negative regulation of FLT3 / embryo implantation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Constitutive Signaling by NOTCH1 HD Domain Mutants / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1,TRAF6-dependent induction of TAK1 complex / rescue of stalled ribosome / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B 類似検索 - 分子機能
E3 UFM1-protein ligase 1 / : / : / : / E3 UFM1-protein ligase 1 / E3 UFM1-protein ligase 1-like domain / E3 UFM1-protein ligase 1 C-terminal domain / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ribosomal protein L30e ...E3 UFM1-protein ligase 1 / : / : / : / E3 UFM1-protein ligase 1 / E3 UFM1-protein ligase 1-like domain / E3 UFM1-protein ligase 1 C-terminal domain / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ribosomal protein L30e / Ribosomal protein L28e / Ribosomal L15/L27a, N-terminal / Ribosomal protein L2, archaeal-type / Ribosomal protein L23 / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / Ribosomal protein L19e, C-terminal domain / metallochaperone-like domain / TRASH domain / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein L13e, conserved site / Ribosomal protein L13e signature. / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal L22e protein family / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / Ribosomal protein L10e / Ribosomal protein L44e signature. / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / Ribosomal protein L13e / Ribosomal protein L13e / Ribosomal protein L19/L19e conserved site / Ribosomal protein L19, eukaryotic / Ribosomal protein L19e signature. / : / 60S ribosomal protein L18a/ L20, eukaryotes / Ribosomal protein L6e signature. / : / Ribosomal protein L44e / Ribosomal protein L44 / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. / Ribosomal protein L5 eukaryotic, C-terminal / 50S ribosomal protein L18Ae/60S ribosomal protein L20 and L18a / Ribosomal L40e family / Ribosomal L18 C-terminal region / Ribosomal protein 50S-L18Ae/60S-L20/60S-L18A / Ribosomal proteins 50S-L18Ae/60S-L20/60S-L18A / Ribosomal protein 60S L18 and 50S L18e / Ribosomal protein L30e signature 1. / Ribosomal_L40e / Ribosomal protein L40e / Ribosomal protein L40e superfamily / Ribosomal protein L18/L18-A/B/e, conserved site / Ribosomal protein L18e signature. / Ribosomal protein L23/L25, N-terminal / : / Ribosomal protein L23, N-terminal domain / Eukaryotic Ribosomal Protein L27, KOW domain / Ribosomal Protein L6, KOW domain / Ribosomal protein L36e signature. / Ribosomal protein L35Ae, conserved site / Ribosomal protein L30e signature 2. / Ribosomal protein L35Ae signature. / Ribosomal protein L27e / Ribosomal protein L27e superfamily / Ribosomal L27e protein family / Ribosomal protein L30e, conserved site / Ribosomal protein L39e, conserved site / Ribosomal protein L39e signature. / 60S ribosomal protein L19 / : / Ribosomal protein L13, eukaryotic/archaeal / Ribosomal protein L6e / Ribosomal protein L34Ae / Ribosomal protein L34e / Ribosomal protein L30/YlxQ / Ribosomal protein L7A/L8 / 60S ribosomal protein L6E / 60S ribosomal protein L35 / Ribosomal protein L18e / Ribosomal_L19e / 60S ribosomal protein L4, C-terminal domain / 60S ribosomal protein L4 C-terminal domain / Ribosomal protein L19/L19e / Ribosomal protein L7, eukaryotic / Ribosomal protein L19/L19e, domain 1 / Ribosomal protein L31e, conserved site / Ribosomal protein L19/L19e superfamily / Ribosomal protein L19e, N-terminal domain / Ribosomal protein L31e signature. / Ribosomal protein L30, N-terminal 類似検索 - ドメイン・相同性
Ribosomal protein L37 / E3 UFM1-protein ligase 1 / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein eL13 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL22 / Large ribosomal subunit protein uL4 ...Ribosomal protein L37 / E3 UFM1-protein ligase 1 / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein eL13 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL22 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein uL13 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein eL28 / Large ribosomal subunit protein eL29 / Large ribosomal subunit protein eL34 / Large ribosomal subunit protein eL14 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein eL15 / Large ribosomal subunit protein eL27 / Large ribosomal subunit protein eL43 / Large ribosomal subunit protein eL8 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein uL14 / Large ribosomal subunit protein eL30 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein eL31 / Large ribosomal subunit protein eL32 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein uL2 / Ubiquitin-ribosomal protein eL40 fusion protein / Large ribosomal subunit protein eL38 / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein eL42 / Large ribosomal subunit protein eL19 / Large ribosomal subunit protein eL20 / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein eL18 / Large ribosomal subunit protein eL36 類似検索 - 構成要素
Biotechnology and Biological Sciences Research Council (BBSRC)
BB/T008172/1
英国
European Research Council (ERC)
677623
European Union
Medical Research Council (MRC, United Kingdom)
MC_UU_00018/3
英国
引用
ジャーナル: Nature / 年: 2024 タイトル: The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER translocons. 著者: Linda Makhlouf / Joshua J Peter / Helge M Magnussen / Rohan Thakur / David Millrine / Thomas C Minshull / Grace Harrison / Joby Varghese / Frederic Lamoliatte / Martina Foglizzo / Thomas ...著者: Linda Makhlouf / Joshua J Peter / Helge M Magnussen / Rohan Thakur / David Millrine / Thomas C Minshull / Grace Harrison / Joby Varghese / Frederic Lamoliatte / Martina Foglizzo / Thomas Macartney / Antonio N Calabrese / Elton Zeqiraj / Yogesh Kulathu / 要旨: Stalled ribosomes at the endoplasmic reticulum (ER) are covalently modified with the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26 (also known as uL24). This modification, ...Stalled ribosomes at the endoplasmic reticulum (ER) are covalently modified with the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26 (also known as uL24). This modification, which is known as UFMylation, is orchestrated by the UFM1 ribosome E3 ligase (UREL) complex, comprising UFL1, UFBP1 and CDK5RAP3 (ref. ). However, the catalytic mechanism of UREL and the functional consequences of UFMylation are unclear. Here we present cryo-electron microscopy structures of UREL bound to 60S ribosomes, revealing the basis of its substrate specificity. UREL wraps around the 60S subunit to form a C-shaped clamp architecture that blocks the tRNA-binding sites at one end, and the peptide exit tunnel at the other. A UFL1 loop inserts into and remodels the peptidyl transferase centre. These features of UREL suggest a crucial function for UFMylation in the release and recycling of stalled or terminated ribosomes from the ER membrane. In the absence of functional UREL, 60S-SEC61 translocon complexes accumulate at the ER membrane, demonstrating that UFMylation is necessary for releasing SEC61 from 60S subunits. Notably, this release is facilitated by a functional switch of UREL from a 'writer' to a 'reader' module that recognizes its product-UFMylated 60S ribosomes. Collectively, we identify a fundamental role for UREL in dissociating 60S subunits from the SEC61 translocon and the basis for UFMylation in regulating protein homeostasis at the ER.