InterPro domain: IPR044046

UBR box family is a unique class of E3 ligases that recognise N-degrons or structurally related determinants for ubiquitin-dependent proteolysis. They belong to the N-end rule pathway which relates the identity of the N-terminal residue of a protein with its half-life, recognising destabilising ones. Some of the functions of this pathway include the control of peptide import, the fidelity of chromosome segregation, the regulation of apoptosis, as well as regulation of meiosis in yeasts and metazoans, leaf senescence in plants, and cardiovascular development in mammals [ 1 ]. These proteins contain an N-terminal UBR box (a substrate-binding domain), which is highly conserved among UBR family members, a cysteine- and histidine-rich RING (RING-H2) domain, which is present in a larger class of E3 ubiquitin ligases and some additional domains that vary among UBR family members, like these described in UBR1 [ 2 ]: ClpS, a region of sequence similarity to prokaryotic ClpS which acts as an accessory subunit that contributes to recognition of degrons by the ATP-dependent protease ClpAP, a BRR (basic residue-rich region), a conserved motif that contributes to the binding of yeast UBR1 to the E2 enzyme RAD6, and conserved regions [ 3 , 3 , 4 ].

This entry represents the C-terminal domain which includes a conserved region found in E3 ubiquitin-protein ligase UBR1, 2, 3 from animals, UBR1/11 from fission yeast, and also in PRT6 from Arabidopsis thaliana [ 5 ].

1. A family of mammalian E3 ubiquitin ligases that contain the UBR box motif and recognize N-degrons. Mol. Cell. Biol. 25, 7120-36
2. Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome). Nat. Genet. 37, 1345-50
3. The UBR-1 ubiquitin ligase regulates glutamate metabolism to generate coordinated motor pattern in Caenorhabditis elegans. PLoS Genet. 14, e1007303
4. Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination. PLoS Genet. 12, e1006054
5. Distinct branches of the N-end rule pathway modulate the plant immune response. New Phytol. 221, 988-1000