Scientific Background: FANCL or Fanconi anemia complementation group L is a member of the Fanconi anemia complementation group. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. FANCL is crucial in the FA pathway as the catalytic subunit required for monoubiquitination of FANCD2 (1). UBE2W interacts with FANCL and regulates the monoubiquitination of Fanconi anemia protein FANCD2 (2).
2. Zhang, Y.et.al: UBE2W interacts with FANCL and regulates the monoubiquitination of Fanconi anemia protein FANCD2. Molec. Cells 31: 113-122, 2011.
NCBI and Uniprot Product Information
NCBI Description
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]
Uniprot Description
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.
Research Articles on FANCL
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Product Notes
The FANCL fancl (Catalog #AAA515181) is a Recombinant Protein produced from Sf9 insect cells and is intended for research purposes only. The product is available for immediate purchase. The tag for this protein is GST tag!!Expression System||Sf9 insect cells using baculovirus!!Source Note||Recombinant full-length human FANCL was expressed by baculovirus in Sf9 insect cells. AAA Biotech's FANCL can be used in a range of immunoassay formats including, but not limited to, Western Blot (WB). Researchers should empirically determine the suitability of the FANCL fancl for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "FANCL, Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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