E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. May be involved in pancreatic homeostasis. Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth.
Broadly expressed, with highest levels in skeletal muscle, kidney and pancreas. Present in acinar cells of the pancreas (at protein level).
Protein modification; protein ubiquitination.
Involvement in disease
Defects in UBR1 are a cause of Johanson-Blizzard syndrome (JBS) [MIM:243800]. This disorder includes congenital exocrine pancreatic insufficiency, multiple malformations such as nasal wing aplasia, and frequent mental retardation. Pancreas of individuals with JBS do not express UBR1 and show intrauterine-onset destructive pancreatitis.
Belongs to the UBR1 family. Contains 1 RING-type zinc finger. Contains 1 UBR-type zinc finger.
Expressed in fetal pancreas.
The RING-H2 zinc finger is an atypical RING finger with a His ligand in place of the fourth Cys of the classical motif.
Phosphorylated upon DNA damage, probably by ATM or ATR.