UBR5
UBR5 (ubiquitin protein ligase E3 component n-recognin 5, also known as EDD, EDD1, DD5 and HYD) is a HECT-family E3 ubiquitin-protein ligase. It acts mainly as a ubiquitin chain elongator in protein quality control pathways in the cytoplasm and nucleus. Browse Assay Genie's current range of UBR5 research reagents below, or read on for the biology behind the target.
UBR5 is an E3 ubiquitin-protein ligase involved in several protein quality control pathways in the cytoplasm and nucleus. It mainly extends substrates that have already been ubiquitinated. As a component of the N-end rule pathway, it ubiquitinates proteins carrying destabilising N-terminal residues and recognises type-1 N-degrons containing positively charged amino acids (Arg, Lys and His), leading to their degradation. Together with UBR4, it forms a cytoplasmic pathway that limits protein aggregation by assembling heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, which are then recognised by the segregase p97/VCP and degraded by the proteasome. With ITCH, it catalyses 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP.
In the nucleus, UBR5 is the catalytic component of a quality control pathway that degrades unpaired transcription factors, meaning those not assembled into functional multiprotein complexes. Reported substrates include MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1, as well as ligand-bound nuclear receptors such as ESR1, NR1H3, NR3C1, PGR, RARA, RXRA and VDR when they are not associated with NCOA coactivators. UBR5 also polyubiquitinates and activates CDK9, suppresses RNF168 to limit the spread of ubiquitinated chromatin at DNA damage sites, regulates TopBP1, and promotes disassembly of the mitotic checkpoint complex by ubiquitinating BUB1B, BUB3 and CDC20. It positively regulates canonical Wnt signalling by stabilising CTNNB1 and promoting degradation of TLE3, and it inhibits hedgehog signalling in skeletal tissue. It is essential for extraembryonic development.
The UBR5 gene belongs to the HECT (homology to E6-AP carboxyl terminus) family and was described as a progestin-induced protein. It lies on chromosome 8q22, a region disrupted in a variety of cancers, and may contribute to regulation of cell proliferation or differentiation. HGNC lists it among the ubiquitin protein ligase E3 component n-recognins and the HECT domain E3 ligases; a previous name was E3 ubiquitin protein ligase, HECT domain containing, 1. Mouse and rat orthologs are designated Ubr5.
UBR5 builds branched ubiquitin chains that direct substrates to p97/VCP and the proteasome, making it a model for studying chain elongation.
UBR5 degrades unpaired transcription factors and ligand-bound nuclear receptors lacking coactivators, linking ubiquitination to transcriptional regulation.
UBR5 suppresses RNF168 and regulates TopBP1, guarding against excessive spreading of ubiquitinated chromatin at damaged chromosomes.
UBR5 stabilises CTNNB1 to promote canonical Wnt signalling and inhibits hedgehog signalling in maintaining skeletal tissue homeostasis.
UBR5 is an E3 ubiquitin-protein ligase that mainly elongates ubiquitin chains on pre-ubiquitinated substrates. It functions in the N-end rule pathway, cytoplasmic and nuclear protein quality control, DNA damage response, mitotic checkpoint complex disassembly and Wnt signalling.
UBR5 is also called EDD, EDD1, DD5, HYD and KIAA0896. Its earlier name was E3 ubiquitin protein ligase, HECT domain containing, 1. UniProt names the protein E3 ubiquitin-protein ligase UBR5, and it belongs to the UBR5 family.
Mouse and rat both have a Ubr5 ortholog. The human gene maps to chromosome 8q22, a region disrupted in a variety of cancers, and may regulate cell proliferation or differentiation. Check the datasheet of any product for its validated reactivity.
Other N-recognins and ubiquitin pathway proteins that work alongside UBR5 in protein quality control.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O95071; product specifications from Assay Genie datasheets.