PELI1 - pellino E3 ubiquitin protein ligase 1 (human)
Gene
Symbol
Taxonomy
Dates
- Create:2016-09-14
- Modify:2025-01-14
Description
Enables ubiquitin-ubiquitin ligase activity. Involved in several processes, including negative regulation of TORC1 signaling; negative regulation of necroptotic process; and protein polyubiquitination. Is active in site of double-strand break. Implicated in colorectal cancer.
- E3 ubiquitin-protein ligase pellino homolog 1
- RING-type E3 ubiquitin transferase pellino homolog 1
- pellino homolog 1
- pellino-1
- pellino-related intracellular-signaling molecule
- protein pellino homolog 1
E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PMID: 12496252, PMID: 17675297, PMID: 29883609, PMID: 30952868). Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6 (PMID: 12496252, PMID: 17675297). Acts as a positive regulator of inflammatory response in microglia through activation of NF-kappa-B and MAP kinase (By similarity). Mediates 'Lys-63'-linked polyubiquitination of IRAK1 allowing subsequent NF-kappa-B activation (PMID: 12496252, PMID: 17675297). Conjugates 'Lys-63'-linked ubiquitin chains to the adapter protein ASC/PYCARD, which in turn is crucial for NLRP3 inflammasome activation (PMID: 34706239). Mediates 'Lys-48'-linked polyubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation; preferentially recognizes and mediates the degradation of the 'Thr-182' phosphorylated form of RIPK3 (PMID: 29883609). Negatively regulates necroptosis by reducing RIPK3 expression (PMID: 29883609). Mediates 'Lys-63'-linked ubiquitination of RIPK1 (PMID: 29883609). Following phosphorylation by ATM, catalyzes 'Lys-63'-linked ubiquitination of NBN, promoting DNA repair via homologous recombination (PMID: 30952868). Negatively regulates activation of the metabolic mTORC1 signaling pathway by mediating 'Lys-63'-linked ubiquitination of mTORC1-inhibitory protein TSC1 and thereby promoting TSC1/TSC2 complex stability (PMID: 33215753).
Highly accurate protein structure prediction with AlphaFold. Nature. 2021 Aug;596(7873):583-589. DOI:10.1038/s41586-021-03819-2. PMID:34265844; PMCID:PMC8371605
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