InterPro domain: IPR043003

This superfamily represents the third of three UBC-like domains found in the FANCL protein, which is the catalytic E3 ubiquitin ligase subunit of the FA complex (Fanconi anaemia). Structurally, it consists of 3 alpha helices and 4 beta strands.

FancL is the ubiquitin ligase protein that mediates ubiquitination of FancD2, a key step in the DNA damage pathway [ 1 , 2 ]. FancL belongs to the multisubunit Fanconi anemia (FA) complex, which is composed of subunits: FancA, FancB, FancC, FancE, FancF, FancG, FancL/PHF9 and FancM. The WD repeats are required for interaction of FancL with other subunits of the FA complex [ 3 ].

In humans defects in FancL are a cause of Fanconi anemia (FA) (OMIM:227650), and the FA complex is not found in FA patients. FA is a genetically heterogeneous, autosomal recessive disorder characterised by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.

1. A requirement of FancL and FancD2 monoubiquitination in DNA repair. Genes Cells 12, 299-310
2. Drosophila homologs of FANCD2 and FANCL function in DNA repair. DNA Repair (Amst.) 5, 1317-26
3. The WD40 repeats of FANCL are required for Fanconi anemia core complex assembly. J. Biol. Chem. 281, 10896-905