Recombinant Human His6-HR6A/UBE2A Protein, CF

Homolog of Rad6 A (HR6A), also known as Ubiquitin-conjugating Enzyme E2A (UBE2A), is a ubiquitously expressed member of the Ubiquitin-conjugating (E2) enzyme family that is highly expressed in the brain and heart (1). HR6A/UBE2A has a predicted molecular weight of 17 kDa. The human protein shares 100% amino acid sequence identity with the mouse and rat orthologs. Like other E2 family members, HR6A/UBE2A has an E2 catalytic core domain that contains an active site cysteine residue required for the formation of a thioester bond with Ubiquitin (2). HR6A/UBE2A is involved in many cellular processes including protein degradation, transcriptional regulation, and the DNA damage response. HR6A/UBE2A functions with the UBR2 Ubiquitin ligase (E3) to mediate ubiquitination of target substrates degraded through the N-end rule proteolytic pathway (3). HR6A/UBE2A also interacts with the human BRE1 E3 to ubiquitinate Histone H2B on Lys120, which promotes transcription via methylation of Histone H3 on Lys4 (4). HR6A/UBE2A is activated via phosphorylation on Ser120 by CDK9 following exposure to UVC irradiation and HR6A/UBE2A-RAD18-dependent ubiquitination of PCNA is required for DNA damage tolerance (5-7). HR6A/UBE2A also regulates the mRNA and protein levels of p53 (8). Physiologically, this enzyme is required in female mice for the production of viable offspring (9). Mutations in human HR6A/UBE2A cause UBE2A deficiency syndrome in males, which is characterized by intellectual disability, seizures, absent speech, and urogenital and skin anomalies (10-12). This protein has an N-terminal His₆-tag. (Accession NP_003327)