InterPro domain: IPR041298

This entry represents type 3 UBZ found in DNA polymerase eta ( 2.7.7.7 ). It is important in the recruitment of the polymerase to the stalled replication machinery in translesion synthesis. The UBZ domain adopts a classical C2H2 zinc-finger structure characterized by a beta-beta-alpha fold [ 1 ].

The ubiquitin-binding zinc finger (UBZ) is a type of zinc-coordinating beta- beta-alpha fold domain found mainly in proteins involved in DNA repair and transcriptional regulation. UBZ domains coordinate a zinc ion with cysteine or histidine residues; depending on their amino acid sequence, UBZ domains are classified into several families [ 2 , 3 ]. Type 1 UBZs are CCHH-type zinc fingers found in tandem UBZ domains of TAX1-binding protein 1 (TAX1BP1) [ 4 , 5 , 6 ], type 2 UBZs are CCHC-type zinc fingers found in FAAP20 which is a subunit of the Fanconi anemia (FA) core complex [ 7 , 8 ], type 3 UBZs are CCHH-type zinc fingers found only in the Y-family translesion polymerase eta [ 9 , 9 , 10 ], and type 4 UBZs are CCHC-type zinc fingers found in Y-family translesion polymerase kappa, Werner helicase-interacting protein 1 (WRNIP1), and Rad18 [ 11 , 12 , 13 ].

The UBZ domain consists of two short antiparallel beta-strands followed by one alpha-helix. The alpha-helix packs against the beta-strands with a zinc ion sandwiched between the alpha-helix and the beta-strands. The zinc ion is coordinated by two cysteines located on the fingertip formed by the beta- strands and two histidines [ 14 , 14 ] or one hisidine and one cysteine [ 14 ] on the alpha-helix [ 14 ].

1. Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase eta. EMBO Rep. 8, 247-51
2. Ubiquitin-binding domains and their role in the DNA damage response. DNA Repair (Amst.) 8, 544-56
3. A novel mode of ubiquitin recognition by the ubiquitin-binding zinc finger domain of WRNIP1. FEBS J. 283, 2004-17
4. The structure of TAX1BP1 UBZ1+2 provides insight into target specificity and adaptability. J. Mol. Biol. 426, 674-90
5. Molecular basis of ubiquitin recognition by the autophagy receptor CALCOCO2. Autophagy 11, 1775-89
6. Recruitment of TBK1 to cytosol-invading Salmonella induces WIPI2-dependent antibacterial autophagy. EMBO J. 35, 1779-92
7. Ubiquitin recognition by FAAP20 expands the complex interface beyond the canonical UBZ domain. Nucleic Acids Res. 42, 13997-4005
8. Structural basis for ubiquitin recognition by ubiquitin-binding zinc finger of FAAP20. PLoS ONE 10, e0120887
9. The noncatalytic C-terminus of AtPOLK Y-family DNA polymerase affects synthesis fidelity, mismatch extension and translesion replication. FEBS J. 274, 3340-50
10. The unusual UBZ domain of Saccharomyces cerevisiae polymerase ?. DNA Repair (Amst.) 9, 1130-41
11. RAD18-dependent recruitment of SNM1A to DNA repair complexes by a ubiquitin-binding zinc finger. J. Biol. Chem. 285, 19085-91
12. NMR structure of the human Rad18 zinc finger in complex with ubiquitin defines a class of UBZ domains in proteins linked to the DNA damage response. Biochemistry 53, 5895-906
13. Distinct functional roles for the two SLX4 ubiquitin-binding UBZ domains mutated in Fanconi anemia. J. Cell. Sci. 127, 2811-7