Disease relevance of UBR1

• Pancreas of individuals with Johanson-Blizzard syndrome did not express UBR1 and had intrauterine-onset destructive pancreatitis [1].
• UBR1(-/-) mice are viable but have defects that include pancreatic insufficiency, similarly to UBR1(-/-) human patients with Johanson-Blizzard syndrome [2].

Psychiatry related information on UBR1

• Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome) [1].

High impact information on UBR1

• We mapped the disease-associated locus to chromosome 15q14-21.1 and identified mutations, mostly truncating ones, in the gene UBR1 in 12 unrelated families with Johanson-Blizzard syndrome [1].
• Moreover, UBR1 depletion in HeLa cells, which constitutively express UBR1 at a high level, enhances both c-Fos expression and cell growth, whereas ERK5 depletion reduces both of them [3].
• ERK5 inhibits the nuclear export of c-Fos by phosphorylating Thr232 in the c-Fos NES(221-233) and disrupts the interaction of c-Fos with UBR1 by phosphorylating Ser32 [3].
• UBR1 and UBR2 are 46% identical and appear to be indistinguishable in their recognition of N-degrons [2].
• The mammalian genome encodes at least seven UBR box-containing proteins, which we propose to call UBR1 to UBR7 [4].

Anatomical context of UBR1

• RECQL4 from HeLa cells was isolated as a stable complex with UBR1 and UBR2 [5].

Other interactions of UBR1

• RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway [5].

References