One of the proteolytic pathways of the ubiquitin system is the N-end rule pathway.  The recognition component of this pathway is encoded by the UBR1 gene.  The function of this recognition component is to bind to destabilizing N-terminal residues of substrate protein.  This in turn leads to the formation of a substrate-linked multiubiquitin chain, eventually causing the degradation of the marked protein.  

Mutations in this gene cause Johanson-Blizzard syndrome ( JBS). 

The UBR1 gene is located on the long arm of chromosome 15.  It consists of 47 exons and spans 161 kb of genomic DNA.  It codes for the E3 ubiquitin-protein ligase UBR1 which consists of 1749 amino acids.  The UBR1 protein contains several evolutionarily conserved domains, including the UBR box, the BRR (basic residues-rich) domain, the Cys/His-rich RING-H2 domain, and the AI (autoinhibitory) domain.  The UBR box is instrumental in providing the specificity to the protein to target the destabilizing N-terminal residues.  Several mutations have been described in the literature.  Most mutations leading to are nonsense, frameshift or splice-site mutations that abolish UBR1 activity, although specific missense mutations have also been reported.