The N-end rule pathway is one proteolytic pathway of the ubiquitin system. The recognition component of this pathway, encoded by this gene, binds to a destabilizing N-terminal residue of a substrate protein and participates in the formation of a substrate-linked multiubiquitin chain. This leads to the eventual degradation of the substrate protein. The protein described in this record has a RING-type zinc finger and a UBR-type zinc finger. Mutations in this gene have been associated with Johanson-Blizzard syndrome. [provided by RefSeq, Jul 2008],developmental stage:Expressed in fetal pancreas.,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.,domain:The RING-H2 zinc finger is an atypical RING finger with a His ligand in place of the fourth Cys of the classical motif.,function: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.,pathway:Protein modification, protein ubiquitination.,PTM:Phosphorylated upon DNA damage, probably by ATM or ATR.,similarity:Belongs to the UBR1 family.,similarity:Contains 1 RING-type zinc finger.,similarity:Contains 1 UBR-type zinc finger.,subunit:Interacts with RECQL4.,tissue specificity:Broadly expressed, with highest levels in skeletal muscle, kidney and pancreas. Present in acinar cells of the pancreas (at protein level).,
