UBE1 is an E1 enzyme within the E1, E2, E3 cascade which conjugates Ub to protein substrates.UBE1 activates Ub by catalyzing an ATP – dependent reaction; Ub is conjugated onto the catalytic Cys residue of UBE1 by formation of a thioester bond.The activated Ub is then passed on to a Ub-conjugating enzyme E2; Ub charged E2 binds a Ub ligase E3 that directly binds substrate proteins. Ub is transferred to the HECT domain E3s prior to being conjugated on substrate proteins. For RING domain E3s, Ub is transferred directly from an E2 to substrate proteins.