Pellino 1

E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:12496252, PubMed:17675297, PubMed:29883609, PubMed:30952868). Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6 (PubMed:12496252, PubMed: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 (PubMed:12496252, PubMed:17675297). Conjugates 'Lys-63'-linked ubiquitin chains to the adapter protein ASC/PYCARD, which in turn is crucial for NLRP3 inflammasome activation (PubMed: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 (PubMed:29883609). Negatively regulates necroptosis by reducing RIPK3 expression (PubMed:29883609). Mediates 'Lys-63'-linked ubiquitination of RIPK1 (PubMed:29883609). Following phosphorylation by ATM, catalyzes 'Lys-63'-linked ubiquitination of NBN, promoting DNA repair via homologous recombination (PubMed: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 (PubMed:33215753).

Protein modification; protein ubiquitination.

Phosphorylation by IRAK1 and IRAK4 enhances its E3 ligase activity (PubMed:17997719). Phosphorylated by ATM in response to DNA damage, promoting localization to DNA double-strand breaks (DSBs) and ability to mediate 'Lys-63'-linked ubiquitination of NBN (PubMed:30952868).

Sumoylated.

Belongs to the pellino family.

Expressed at high levels in normal skin but decreased in keratinocytes from toxic epidermal necrolysis (TEN) patients (at protein level).

• Chromosome
• Localizes to DNA double-strand breaks (DSBs) in response to DNA damage.

PRISM, PELI1, E3 ubiquitin-protein ligase pellino homolog 1, Pellino-1, Pellino-related intracellular-signaling molecule, RING-type E3 ubiquitin transferase pellino homolog 1

• entrezGene:57162
• entrezGene:57161
• omim:614798
• omim:614797
• swissprot:Q96FA3
• swissprot:Q9HAT8

Proteins

Immunology & Infectious Disease

46286Da