Recombinant Mouse E3 ubiquitin-protein ligase UBR1 (Ubr1), partial

Function

E3 ubiquitin-protein ligase which is a component of the N-end rule pathway (PubMed:11689692, PubMed:14585983, PubMed:16311597, PubMed:19008229). Recognizes and binds proteins bearing specific N-terminal residues (N-degrons) that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (PubMed:11689692, PubMed:14585983, PubMed:16311597, PubMed:19008229). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:19008229). Does not ubiquitinate proteins that are acetylated at the N-terminus (By similarity). In contrast, it strongly binds methylated N-degrons (By similarity). Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth (By similarity)

Subcellular Location

Cytoplasm, cytosol

Tissue Specificity

Present in skeletal muscle and liver (at protein level). Broadly expressed, with highest levels in skeletal muscle and heart. Expressed in acinar cells of the pancreas. In testes, expressed primarily in spermatogonia

Subunit

Interacts with RECQL4

Pathway

Protein modification; protein ubiquitination

• Kwon Y.T. et al. The mouse and human genes encoding the recognition component of the N-end rule pathway. — Proc. Natl. Acad. Sci. U.S.A. (1998)
• Church D.M. et al. Lineage-specific biology revealed by a finished genome assembly of the mouse. — PLoS Biol. (2009)
• Carninci P. et al. The transcriptional landscape of the mammalian genome. — Science (2005)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Kwon Y.T. et al. Construction and analysis of mouse strains lacking the ubiquitin ligase UBR1 (E3alpha) of the N-end rule pathway. — Mol. Cell. Biol. (2001)
• Kwon Y.T. et al. Female lethality and apoptosis of spermatocytes in mice lacking the UBR2 ubiquitin ligase of the N-end rule pathway. — Mol. Cell. Biol. (2003)
• Kwak K.S. et al. Regulation of protein catabolism by muscle-specific and cytokine-inducible ubiquitin ligase E3alpha-II during cancer cachexia. — Cancer Res. (2004)
• Zenker M. et al. Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome). — Nat. Genet. (2005)