FANCL Recombinant Protein

The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group L. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Function: Ubiquitin ligase protein that mediates monoubiquitination of FANCD2, a key step in the DNA damage pathway. Also mediates monoubiquitination of FANCI. May stimulate the ubiquitin release from UBE2W. May be required for proper primordial germ cell proliferation in the embryonic stage, whereas it is probably not needed for spermatogonial proliferation after birth. Ref.5 Ref.8 Ref.9 Ref.11 Ref.12

Pathway: Protein modification; protein ubiquitination.

Subunit structure: Interacts with GGN

By similarity. Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. The complex is not found in FA patients. In complex with FANCF, FANCA and FANCG, but not with FANCC, nor FANCE, interacts with HES1; this interaction may be essential for the stability and nuclear localization of FA core complex proteins. Interacts with FANCI. Interacts (via the RING-type zinc finger) with UBE2T and UBE2W. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14

Subcellular location: Cytoplasm. Nucleus Ref.5 Ref.10.

Domain: The UBC-RWD region (URD) region mediates interaction with FANCI and FANCD2 (Ref.14).

Post-translational modification: The RING-type zinc finger domain is monoubiquitinated in the presence of UBE2T and UBE2W.

Involvement in disease: Fanconi anemia complementation group L (FANCL) [MIM:614083]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6

Sequence similarities: Contains 1 RING-type zinc finger.

Caution: Although Ref.4 reports that it contains a PHD-type zinc finger, it contains a RING-type zinc finger. Moreover, PHD-type zinc fingers do not have any ubiquitin ligase activity.